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  • 151.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Verheul, M. K.
    Ronnelid, J.
    Holmdahl, R.
    Toes, R. E. M.
    Klareskog, L.
    Trouw, L. A.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    The presence of anti-carbamylated protein antibodies prior to onset of symptoms of rheumatoid arthritis (RA) is associated with radiological progression in early RA2014Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr Suppl. 127, Meeting Abstract: PP109, s. 21-22Artikel i tidskrift (Övrigt vetenskapligt)
  • 152.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Verheul, M. K.
    Ronnelid, J.
    Toes, R. E.
    Klareskog, L.
    Trouw, L. L.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Anti-carbamylated protein antibodies precede the onset of symptoms of rheumatoid arthritis in a Swedish biobank cohort2014Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, s. 397-398Artikel i tidskrift (Övrigt vetenskapligt)
  • 153. Brink, Mikael
    et al.
    Verheul, Marije K.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Berglin, Ewa
    Holmdahl, Rikard
    Toes, Rene E. M.
    Klareskog, Lars
    Trouw, Leendert A.
    Rantapaa-Dahlqvist, Solbritt
    Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage2015Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 17, artikel-id 25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2. Methods: A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia). Results: The concentration of anti-CarP antibodies was significantly increased in the pre-symptomatic individuals compared with controls (P < 0.001) and also increased significantly after disease onset (P < 0.001). The sensitivity for anti-CarP antibodies in the pre-symptomatic individuals was 13.9% (95% CI: 11 to 17.6) and 42.2% (95% CI: 35.4 to 49.3) following development of RA. Anti-CarP antibody positivity was found in 5.1% to 13.3% of individuals negative for anti-CCP2 or ACPA specificities. Presence of anti-CarP antibodies was significantly related to radiological destruction at baseline, at 24 months and also to radiological change (P < 0.05, all). Conclusions: The results indicate that anti-CarP antibodies are associated with disease development, even after adjusting for the presence of different ACPA fine specificities, and in anti-CCP2 negative individuals and contribute to the identification of a subset of patients with worse radiological progression of the disease independent of ACPA.

  • 154.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Verheul, Marije K.
    Rönnelid, Johan
    Berglin, Ewa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Holmdahl, Rikard
    Toes, Rene E. M.
    Klareskog, Lars
    Trouw, Leendert A.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage2015Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 17, artikel-id 25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2. Methods: A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia). Results: The concentration of anti-CarP antibodies was significantly increased in the pre-symptomatic individuals compared with controls (P < 0.001) and also increased significantly after disease onset (P < 0.001). The sensitivity for anti-CarP antibodies in the pre-symptomatic individuals was 13.9% (95% CI: 11 to 17.6) and 42.2% (95% CI: 35.4 to 49.3) following development of RA. Anti-CarP antibody positivity was found in 5.1% to 13.3% of individuals negative for anti-CCP2 or ACPA specificities. Presence of anti-CarP antibodies was significantly related to radiological destruction at baseline, at 24 months and also to radiological change (P < 0.05, all). Conclusions: The results indicate that anti-CarP antibodies are associated with disease development, even after adjusting for the presence of different ACPA fine specificities, and in anti-CCP2 negative individuals and contribute to the identification of a subset of patients with worse radiological progression of the disease independent of ACPA.

  • 155.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lejon, K
    B-regulatory cells are functionally impaired in patients with rheumatoid arthritis and in their first degree relativesArtikel i tidskrift (Övrigt vetenskapligt)
  • 156.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lejon, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    B Regulatory Cells are Functionally Impaired in Patients with Rheumatoid Arthritis and in Their First-Degree Relatives Compared with Controls2014Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 79, nr 6, s. 450-450Artikel i tidskrift (Övrigt vetenskapligt)
  • 157.
    Brito-Zeron, P.
    et al.
    Hosp CIMA Sanitas, Dept Med, Autoimmune Dis Unit, Barcelona, Spain;Univ Barcelona, Sjogrens Syndrome Res Grp AGAUR, Lab Autoimmune Dis Josep Font,Hosp Clin, IDIBAPS,CELLEX,Dept Autoimmune Dis,ICMiD, Barcelona, Spain.
    Acar-Denizli, N.
    Mimar Sinan Fine Arts Univ, Fac Sci & Letters, Dept Stat, Istanbul, Turkey.
    Ng, W. F.
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
    Zeher, M.
    Univ Debrecen, Fac Med, Div Clin Immunol, Debrecen, Hungary.
    Rasmussen, A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Mandl, T.
    Lund Univ, Skane Univ Hosp Malmo, Dept Rheumatol, Malmo, Sweden.
    Seror, R.
    Univ Paris Sud, Hop Univ Paris Sud, AP HP, Ctr Immunol Viral Infect & Autoimmune Dis,INSERM, Paris, France.
    Li, X.
    Anhui Prov Hosp, Dept Rheumatol & Immunol, Hefei, Anhui, Peoples R China.
    Baldini, C.
    Univ Pisa, Rheumatol Unit, Pisa, Italy.
    Gottenberg, J. -E
    Danda, D.
    Christian Med Coll & Hosp, Dept Clin Immunol & Rheumatol, Vellore, Tamil Nadu, India.
    Quartuccio, L.
    Univ Hosp Santa Maria della Misericordia, Dept Med Area DAME, Clin Rheumatol, Udine, Italy.
    Priori, R.
    Sapienza Univ Rome, Rheumatol Clin, Dept Internal Med & Med Specialties, Rome, Italy.
    Hernandez-Molina, G.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Rheumatol & Immunol, Mexico City, DF, Mexico.
    Armagan, B.
    Hacettepe Univ, Fac Med, Dept Internal Med, Ankara, Turkey.
    Kruize, A. A.
    Univ Med Ctr Utrecht, Dept Rheumatol & Clin Immunol, Utrecht, Netherlands.
    Kwok, S. -K
    Kvarnstrom, M.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Praprotnik, S.
    Univ Med Ctr, Dept Rheumatol, Ljubljana, Slovenia.
    Sene, D.
    Paris Diderot Univ, Lariboisiere Hosp, AP HP, Dept Internal Med, Paris, France.
    Bartoloni, E.
    Univ Perugia, Dept Med, Rheumatol Unit, Perugia, Italy.
    Solans, R.
    Hosp Valle De Hebron, Dept Internal Med, Barcelona, Spain.
    Rischmueller, M.
    Univ Western Australia, Sch Med, Dept Rheumatol, Crawley, Australia.
    Suzuki, Y.
    Kanazawa Univ Hosp, Div Rheumatol, Kanazawa, Ishikawa, Japan.
    Isenberg, D. A.
    UCL, Div Med, Ctr Rheumatol, London, England.
    Valim, V.
    Univ Espirito Santo, Dept Med, Vitoria, Brazil;Univ Hosp HUCAM EBSERH, Vitoria, Brazil.
    Wiland, P.
    Wroclaw Med Hosp, Dept Rheumatol & Internal Med, Wroclaw, Poland.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Fraile, G.
    Hosp Ramon & Cajal, Dept Internal Med, Madrid, Spain.
    Bootsma, H.
    Univ Groningen, Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, Groningen, Netherlands.
    Nakamura, T.
    Nagasaki Univ, Grad Sch Biomed Sci, Dept Radiol & Canc Biol, Nagasaki, Japan.
    Giacomelli, R.
    Univ Aquila, Sch Med, Clin Unit Rheumatol, Laquila, Italy.
    Devauchelle-Pensec, V.
    Brest Univ Hosp, Dept Rheumatol, Brest, France.
    Knopf, A.
    Tech Univ Munich, Klinikum Rechts Isar, Otorhinolaryngol Head & Neck Surg, Munich, Germany.
    Bombardieri, M.
    Queen Mary Univ London, Ctr Expt Med & Rheumatol, London, England.
    Trevisani, V. -F
    Univ Fed Sao Paulo, Sao Paulo, Brazil.
    Hammenfors, D.
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Rheumatol, Bergen, Norway.
    Pasoto, S. G.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Rheumatol, Sao Paulo, Brazil.
    Retamozo, S.
    Univ Nacl Cordoba, Consejo Nacl Invest Cient & Tecn CONICET, Inst Invest Ciencias Salud INICSA, Hosp Privado Univ Cordoba,IUCBC, Cordoba, Argentina.
    Gheita, T. A.
    Cairo Univ, Kasr Al Ainy Sch Med, Dept Rheumatol, Cairo, Egypt.
    Atzeni, F.
    IRCCS Galeazzi Orthopaed Inst, Milan, Italy;Univ Messina, Rheumatol Unit, Messina, Italy.
    Morel, J.
    Montpellier Univ Hosp, Dept Rheumatol, Montpellier, France;Univ Montpellier, Montpellier, France.
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina.
    Horvath, I-F
    Sivils, K. L.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
    Olsson, P.
    Lund Univ, Skane Univ Hosp Malmo, Dept Rheumatol, Malmo, Sweden.
    De Vita, S.
    Univ Hosp Santa Maria della Misericordia, Dept Med Area DAME, Clin Rheumatol, Udine, Italy.
    Sanchez-Guerrero, J.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Rheumatol & Immunol, Mexico City, DF, Mexico.
    Kilic, L.
    Hacettepe Univ, Fac Med, Dept Internal Med, Ankara, Turkey.
    Wahren-Herlenius, M.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Mariette, X.
    Univ Paris Sud, Hop Univ Paris Sud, AP HP, Ctr Immunol Viral Infect & Autoimmune Dis,INSERM, Paris, France.
    Ramos-Casals, M.
    Univ Barcelona, Sjogrens Syndrome Res Grp AGAUR, Lab Autoimmune Dis Josep Font,Hosp Clin, IDIBAPS,CELLEX,Dept Autoimmune Dis,ICMiD, Barcelona, Spain.
    How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis: analysis of 10,500 patients (Sjögren Big Data Project)2018Ingår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, nr 3, s. S102-S112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjogren's syndrome (SjS).

    Methods: The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays.

    Results: By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti-La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglobulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for ctyoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESSDAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains).

    Conclusion: We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.

  • 158.
    Brito-Zeron, P.
    et al.
    Hosp CIMA Sanitas, Barcelona, Spain.;Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Msgsu, Istanbul, Turkey..
    Zeher, M.
    Univ Debrecen, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Li, X.
    Anhui Hosp, Hefei, Anhui, Peoples R China..
    Baldini, C.
    Univ Pisa, Pisa, Italy..
    Gottenberg, J-E
    Danda, D.
    CMC, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria, Udine, Italy..
    Hernandez-Molina, G.
    INCMNSZ, Mexico City, DF, Mexico..
    Kruize, A. A.
    UMC, Utrecht, Netherlands..
    Park, S-H
    Kvarnstrom, M.
    Karolinska Inst, Stockholm, Sweden..
    Praprotnik, S.
    UMCL, Ljubljana, Slovenia..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Alunno, A.
    Univ Perugia, Perugia, Italy..
    Solans, R.
    Hosp Valle De Hebron, Barcelona, Spain..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Suzuki, Y.
    Univ Kanazawa, Kanazawa, Ishikawa, Japan..
    Rischmueller, M.
    TQEH, Adelaide, SA, Australia..
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Fraile, G.
    Hosp Ramon & Cajal, Madrid, Spain..
    Wiland, P.
    Med Hosp, Wroclaw, Poland..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands..
    Nakamura, T.
    Univ Nagasaki, Nagasaki, Japan..
    Valim, V.
    UFES, Vitoria, Spain..
    Giacomelli, R.
    Univ Aquila, Laquila, Italy..
    Seror, R.
    Univ Sud, Paris, France..
    Devauchelle-Pensec, V.
    Univ Brest, Brest, France..
    Hofauer, B.
    TUM, Munich, Germany..
    Bombardieri, M.
    QMUL, London, England..
    Trevisani, V.
    Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Minniti, A.
    Sapienza Univ, Rome, Italy..
    Pasoto, S. G.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Morel, J.
    Univ Montpellier, Montpellier, France..
    Retamozo, S.
    INICSA, Cordoba, Argentina..
    Gheita, T. A.
    Cairo Univ, Cairo, Egypt..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Mariette, X.
    Univ Sud, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Baseline Essdai/ Das Scores In 8061 Patients With Primary Sjögren Syndrome: Characterization Of Systemic Disease2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 464-465Artikel i tidskrift (Övrigt vetenskapligt)
  • 159.
    Brito-Zeron, P.
    et al.
    Hosp CIMA Sanitas, Barcelona, Spain.;Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Msgsu, Istanbul, Turkey..
    Zeher, M.
    Univ Debrecen, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Li, X.
    Anhui Hosp, Hefei, Anhui, Peoples R China..
    Baldini, C.
    Univ Pisa, Pisa, Italy..
    Gottenberg, J-E
    Danda, D.
    CMC, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria, Udine, Italy..
    Hernandez-Molina, G.
    INCMNSZ, Mexico City, DF, Mexico..
    Kruize, A. A.
    UMC, Utrecht, Netherlands..
    Park, S-H
    Kvarnstrom, M.
    Karolinska Instit, Stockholm, Sweden..
    Praprotnik, S.
    UMCL, Ljubljana, Slovenia..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Bartoloni, E.
    Univ Perugia, Perugia, Italy..
    Solans, R.
    Hasp Vall Hebron, Barcelona, Spain..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Suzuki, Y.
    Univ Kanazawa, Kanazawa, Ishikawa, Japan..
    Rischmueller, M.
    TQEH, Adelaide, SA, Australia..
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Fraile, G.
    Hosp Ramon & Cajal, Madrid, Spain..
    Sebastian, A.
    Med Hosp, Wroclaw, Poland..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands..
    Nakamura, T.
    Univ Nagasaki, Nagasaki, Japan..
    Valim, V.
    Univ Fed Espirito Santo, Vitoria, Brazil..
    Giacomelli, R.
    Univ Nagasaki, Nagasaki, Japan.;Univ Aquila, Laquila, Italy..
    Seror, R.
    Univ Paris Sud, Paris, France..
    Devauchelle-Pensec, V.
    Univ Brest, Brest, France..
    Hofauer, B.
    TUM, Munich, Germany..
    Bombaidieri, M.
    QMUL, London, England..
    Trevisani, V.
    Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Pasoto, S. G.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Morel, J.
    Univ Montpellier, Montpellier, France..
    Retamozo, S.
    INICSA, Cordoba, Argentina..
    Gheita, T. A.
    Cairo Univ, Cairo, Egypt..
    Atzeni, F.
    L Sacco Univ Hasp, Milan, Italy..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Mariette, X.
    Univ Paris Sud, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Predicting Survival In 6240 Patients With Primary Sjögren' Syndrome (Big Data Sjögren Project)2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 311-311Artikel i tidskrift (Övrigt vetenskapligt)
  • 160.
    Brito-Zeron, P.
    et al.
    Hosp Clínic, Barcelona, Spain.
    Acar-Denizli, N.
    Msgsu, Istanbul, Turkey.
    Zeher, M.
    Univ Debrecen, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Seror, R.
    Univ Paris Sud, Paris, France..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Li, X.
    Anhui Hosp, Hefei, Anhui, Peoples R China..
    Baldini, C.
    Univ Pisa, Pisa, Italy..
    Gottenberg, J. -E
    Danda, D.
    CMC, Vellore, Tamil Nadu, India..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Quartuccio, L.
    Santa Maria, Udine, Italy..
    Hernandez-Molina, G.
    INCMNSZ, Mexico City, DF, Mexico..
    Kruize, A.
    UMC, Utrecht, Netherlands..
    Park, S. -H
    Catholic Univ Korea, Seoul, South Korea..
    Kvarnstrom, M.
    Karolinska Inst, Stockholm, Sweden..
    Praprotnik, S.
    UMCL, Ljubljana, Slovenia..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Bartoloni, E.
    Univ Perugia, Perugia, Italy..
    Solans, R.
    Hosp Valle De Hebron, Barcelona, Spain..
    Suzuki, Y.
    Univ Hosp, Kanazawa, Ishikawa, Japan..
    Isenberg, D.
    UCL, London, England..
    Rischmueller, M.
    TQEH, Adelaide, SA, Australia..
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Fraile, G.
    Hosp Ramon & Cajal, Madrid, Spain..
    Sebastian, A.
    Med Hosp, Wroclaw, Poland..
    Vissink, A.
    Univ Groningen, Groningen, Netherlands..
    Nakamura, T.
    Univ Nagasaki, Nagasaki, Japan..
    Valim, V.
    Univ Fed Espirito Santo, Vitoria, Brazil..
    Giacomelli, R.
    Univ Aquila, Laquila, Italy..
    Devauchelle-Pensec, V.
    Univ Brest, Brest, France..
    Hofauer, B.
    TUM, Munich, Germany..
    Bombardieri, M.
    QMUL, London, England..
    Trevisani, V.
    Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Carsons, S. E.
    Sch Med SBU, Mineola, NY USA..
    Pasoto, S. G.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Morel, J.
    Univ Montpellier, Montpellier, France..
    Retamozo, S.
    INICSA, Cordoba, Argentina..
    Gheita, T. A.
    Cairo Univ, Cairo, Egypt..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Mariette, X.
    Univ Paris Sud, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Analysis Of 9302 Patients From The Big Data International Primary Sjogren Syndrome Cohort: Clinical Presentation At Diagnosis Of European Vs Non-European Patients2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 886-887Artikel i tidskrift (Övrigt vetenskapligt)
  • 161.
    Brito-Zeron, P.
    et al.
    Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Mimar Sinan Univ, Istanbul, Turkey..
    Zeher, M.
    Debrecen Univ, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Seror, R.
    Paris Sud Univ, Paris, France..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Li, X.
    Anhui Hosp, Hefei, Peoples R China..
    Baldini, C.
    Rheumatol Clin, Pisa, Italy..
    Gottenberg, J. -E
    Danda, D.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Hernandez-Molina, G.
    INNSZ, Mexico City, DF, Mexico..
    Kruize, A.
    UMCU, Utrecht, Netherlands..
    Valim, V.
    Espirito Santo Univ, Vitoria, Spain..
    Kvarnstrom, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Bartoloni, E.
    Perugia Univ, Perugia, Italy..
    Praprotnik, S.
    Clin Ctr Univ, Ljubljana, Slovenia..
    Isenberg, D.
    UCL, London, England..
    Solans, R.
    Vall Hebron Hosp, Barcelona, Spain..
    Rischmueller, M.
    Queen Elizabeth Hosp, Woodville, SA, Australia..
    Kwok, S. -K
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Suzuki, Y.
    Kanazawa Univ, Kanazawa, Ishikawa, Japan..
    Giacomelli, R.
    Laquila Univ, Laquila, Italy..
    Devauchelle-Pensec, V.
    Brest Univ Hosp, Brest, France..
    Bombardieri, M.
    QMUL, London, England..
    Hofauer, B.
    Rechts Isar Hosp, Munich, Germany..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands.;Haukeland Hosp, Bergen, Norway..
    Hammenfors, D.
    Fraile, G.
    Ramon Cajal Hosp, Madrid, Spain..
    Carsons, S.
    SUNY Stony Brook, Mineola, NY USA..
    Gheita, T.
    Cairo Univ, Cairo, Egypt..
    Morel, J.
    Montpellier Hosp, Montpellier, France..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Retamozo, S.
    Privado Hosp, Cordoba, Argentina..
    Horvath, I. -F
    Sivils, K.
    OMRF, Oklahoma City, OK USA..
    Theander, E.
    Lund Univ, Malmo, Sweden..
    Sandhya, P.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    De Vita, S.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Sanchez-Guerrero, J.
    INNSZ, Mexico City, DF, Mexico..
    van der Heijden, E.
    UMCU, Utrecht, Netherlands..
    Moca-Trevisano, V.
    Sao Paulo Fed Univ, Sao Paulo, Brazil..
    Wahren-Herlenius, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Mariette, X.
    Paris Sud Univ, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Worldwide Heterogeneous Diagnostic Approach To Primary Sjögren Syndrome in 8315 Patients (EULAR-SS Task Force Big Data Sjögren Project)2016Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, s. 314-315Artikel i tidskrift (Övrigt vetenskapligt)
  • 162.
    Brito-Zeron, P.
    et al.
    Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Mimar Sinan Univ, Istanbul, Turkey..
    Zeher, M.
    Debrecen Univ, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Seror, R.
    Paris Sud Univ, Paris, France..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Li, X.
    Anhui Hosp, Hefei, Peoples R China..
    Baldini, C.
    Rheumatol Clin, Pisa, Italy..
    Gottenberg, J. -E
    Danda, D.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Hernandez-Molina, G.
    INNSZ, Mexico City, DF, Mexico..
    Kruize, A.
    UMCU, Utrecht, Netherlands..
    Valim, V.
    Espirito Santo Univ, Vitoria, Brazil..
    Kvarnstrom, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Gerli, R.
    Perugia Univ, Perugia, Italy..
    Praprotnik, S.
    Clin Ctr Univ, Ljubljana, Slovenia..
    Isenberg, D.
    UCL, London, England..
    Solans, R.
    Vall Hebron Hosp, Barcelona, Spain..
    Rischmueller, M.
    Queen Elizabeth Hosp, Woodville, SA, Australia..
    Park, S. -H
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Suzuki, Y.
    Kanazawa Univ, Kanazawa, Ishikawa, Japan..
    Giacomelli, R.
    LAquila Univ, Laquila, Italy..
    Saraux, A.
    Brest Univ Hosp, Brest, France..
    Bombardieri, M.
    QMUL, London, England..
    Hofauer, B.
    Rechts Isar Hosp, Munich, Germany..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Fraile, G.
    Ramon Cajal Hosp, Madrid, Spain..
    Carsons, S.
    SUNY Stony Brook, Mineola, NY USA..
    Gheita, T.
    Cairo Univ, Cairo, Egypt..
    Morel, J.
    Montpellier Hosp, Montpellier, France..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Retamozo, S.
    Privado Hosp, Cordoba, Argentina..
    Horvath, I. -F
    Sivils, K.
    OMRF, Oklahoma City, OK USA..
    Theander, E.
    Lund Univ, Malmo, Sweden..
    Sandhya, P.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    De Vita, S.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Sanchez-Guerrero, J.
    INNSZ, Mexico City, DF, Mexico..
    van der Heijden, E.
    UMCU, Utrecht, Netherlands..
    Moca-Trevisano, V.
    Sao Paulo Fed Univ, Sao Paulo, Brazil..
    Wahren-Herlenius, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Mariette, X.
    Paris Sud Univ, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Ethnic Differences Strongly Influence The Phenotypic Expression of Primary Sjögren: Study of 7887 Patients from 20 Countries on 5 Continents (EULAR-SS Task Force Big Data Sjögren Project)2016Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, s. 772-772Artikel i tidskrift (Övrigt vetenskapligt)
  • 163.
    Brito-Zeron, Pilar
    et al.
    Hosp Clin Barcelona, CELLEX IDIBAPS, Dept Autoimmune Dis, Barcelona, Spain..
    Retamozo, Soledad
    Hosp Clin Barcelona, CELLEX IDIBAPS, Dept Autoimmune Dis, Barcelona, Spain.;Hosp Privado Ctr Med Cordoba, Rheumatol Unit, Cordoba, Argentina..
    Zeher, Margit
    Univ Debrecen, Debrecen, Hungary..
    Rasmussen, Astrid
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Theander, Elke
    Lund Univ, Skane Univ Hosp Malmo, Malmo, Sweden..
    Gottenberg, Jacques
    Hop Univ Strasbourg, Strasbourg, France..
    Baldini, Chiara
    Univ Pisa, Rheumatol Unit, Pisa, Italy..
    Quartuccio, Luca
    Univ Udine, Santa Maria Misericordia Hosp, Clin Rheumatol, Dept Med & Biol Sci DSMB, I-33100 Udine, Italy..
    Priori, Roberta
    Univ Roma La Sapienza, Rheumatol Unit, I-00185 Rome, Italy..
    Valim, Valeria
    Univ Fed Espirito Santo, Rheumatol, Vitoria, Brazil..
    Kvarnstrom, Marika
    Karolinska Inst, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Kruize, Aike
    Univ Med Ctr Utrecht, Rheumatol & Clin Immunol, Utrecht, Netherlands..
    Hernandez-Molina, Gabriela
    Inst Nacl Ciencias Med Nutr Salvador Zubiran, Immunol & Rheumatol, Mexico City, DF, Mexico..
    Bartoloni-Bocci, Elena
    Univ Perugia, Rheumatol Unit, Dept Med, I-06100 Perugia, Italy..
    Praprotnik, Sonja
    Univ Med Ctr Ljubljana, Dept Rheumatol, Ljubljana, Slovenia..
    Isenberg, David A.
    UCL Div Med, Ctr Rheumatol Res, Rayne Inst, London, England..
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Bombardieri, Michele
    Queen Mary Univ London, Expt Med & Rheumatol, London, England..
    Suzuki, Yasunori
    Kanazawa Univ, Grad Sch Med, Kanazawa, Ishikawa, Japan..
    Solans, Roser
    Hosp Valle De Hebron, Dept Internal Med, Barcelona, Spain..
    Giacomelli, Roberto
    Univ Aquila, I-67100 Laquila, Italy..
    Hammenfors, Daniel S.
    Haukeland Hosp, Dept Rheumatol, N-5021 Bergen, Norway..
    Carsons, Steven E.
    Winthrop Univ Hosp, Rheumatol Allergy & Immunol, Mineola, NY 11501 USA..
    Boostma, Hendrika
    Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands..
    Vollenweider, Cristina F.
    German Hosp, Rheumatol, Buenos Aires, DF, Argentina..
    Atzeni, Fabiola
    L Sacco Univ Hosp Milan, Rheumatol Unit, Milan, Italy..
    Sivils, Kathy
    Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA..
    Mandl, Thomas
    Lund Univ, Dept Rheumatol, Skane Univ Hosp Malmo, Malmo, Sweden..
    De Vita, Salvatore
    Univ Udine, Santa Maria Misericordia Hosp, I-33100 Udine, Italy..
    Wahren-Herlenius, Marie
    Karolinska Inst, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Kawano, Mitsuhiro
    Kanazawa Univ, Div Rheumatol, Grad Sch Med, Kanazawa, Ishikawa, Japan..
    Gerli, Roberto
    Univ Perugia, I-06100 Perugia, Italy..
    Vissink, Arjan
    Univ Groningen, Univ Med Ctr Groningen, Dept Oral & Maxillofacial Surg, Groningen, Netherlands..
    Brun, Johan G.
    Haukeland Hosp, N-5021 Bergen, Norway..
    Trevisani, Virginia
    Univ Fed Sao Paulo, Hlth Evidence Based, Sao Paulo, Brazil..
    Sanchez-Guerrero, Jorge
    Mt Sinai Hosp, Rheumatol, Toronto, ON M5G 1X5, Canada.;Univ Hlth Network, Toronto, ON M5G 1X5, Canada..
    Mariette, Xavier
    Univ Paris 11, Hop Univ Paris Sud, AP HP, Paris, France..
    Ramos-Casals, Manuel
    Hosp Clin Barcelona, CELLEX IDIBAPS, Dept Autoimmune Dis, Barcelona, Spain..
    Big Data International Primary Sjogren Syndrome Registry: Baseline Characterization and Diagnostic Approach in 6047 Patients Fulfilling the 2002 AE Criteria2015Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, nr Suppl. 10, artikel-id 634Artikel i tidskrift (Övrigt vetenskapligt)
  • 164. Brito-Zerón, Pilar
    et al.
    Acar-Denizli, Nihan
    Zeher, Margit
    Rasmussen, Astrid
    Seror, Raphaele
    Theander, Elke
    Li, Xiaomei
    Baldini, Chiara
    Gottenberg, Jacques-Eric
    Danda, Debashish
    Quartuccio, Luca
    Priori, Roberta
    Hernandez-Molina, Gabriela
    Kruize, Aike A
    Valim, Valeria
    Kvarnstrom, Marika
    Sene, Damien
    Gerli, Roberto
    Praprotnik, Sonja
    Isenberg, David
    Solans, Roser
    Rischmueller, Maureen
    Kwok, Seung-Ki
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Suzuki, Yasunori
    Giacomelli, Roberto
    Devauchelle-Pensec, Valerie
    Bombardieri, Michele
    Hofauer, Benedikt
    Bootsma, Hendrika
    Brun, Johan G
    Fraile, Guadalupe
    Carsons, Steven E
    Gheita, Tamer A
    Morel, Jacques
    Vollenveider, Cristina
    Atzeni, Fabiola
    Retamozo, Soledad
    Horvath, Ildiko Fanny
    Sivils, Kathy
    Mandl, Thomas
    Sandhya, Pulukool
    De Vita, Salvatore
    Sanchez-Guerrero, Jorge
    van der Heijden, Eefje
    Trevisani, Virginia Fernandes Moça
    Wahren-Herlenius, Marie
    Mariette, Xavier
    Ramos-Casals, Manuel
    Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients: a cross-sectional study from the Big Data Sjögren Project Consortium2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, nr 6, s. 1042-1050Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis.

    METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed.

    RESULTS: We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69).

    CONCLUSIONS: This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.

  • 165.
    Brorsson, Sofia
    et al.
    Högskolan i Halmstad, Sektionen för ekonomi och teknik (SET), Bio- och miljösystemforskning (BLESS), Biomekanik och biomedicin.
    Pedersen, Eja
    Högskolan i Halmstad, Sektionen för ekonomi och teknik (SET), Bio- och miljösystemforskning (BLESS).
    12-weeks of hand exercise provides better hand function, muscle balance and muscle strength in the rheumatoid arthritis hand2010Ingår i: Abstract Archive Sessions Index 2010, EULAR , 2010Konferensbidrag (Refereegranskat)
    Abstract [en]

    Background:

    Impaired grip ability in RA is due to reduced strength in the flexor muscles as well as by dysfunctional extensor muscles leading to inability to open the hand. Furthermore the extensor muscles are important for stabilization during flexion force production and active for developing a controlled grip force. There is today scientific evidence showing that various forms of hand exercise are beneficial for improving hand function and strength in RA patients (Ronningen and Kjeken 2008; Brorsson, Hilliges et al. 2009). However, comparatively little research has evaluated and specific designed hand exercise program for the extensor muscles controlling the hand and fingers (Weiss, Moore et al. 2004; O'Brien, Jones et al. 2006).

    Objectives:

    The objectives for this study were to evaluate the effect of an exercise program on hand strength, hand function and perceived function of daily life activities among RA patients and to explore the possibility to improve the balance between the extensor and flexor muscle forces in the hand.

    Methods:

    The study group comprised of 20 patients with RA (median disease duration 20 years) that performed a hand exercise program for twelve weeks. The finger extension force was measured with a newly developed device (EX-it), finger flexion force was measured with the Grippit. Hand function was evaluated with the Grip Ability Test (GAT) and self reported questionnaire Disability Arm Shoulder and Hand (DASH).

    Results:

    Hand strength (both extension and flexion force) and hand function improved significantly after twelve weeks. The RA group showed improvement in the results of the DASH questionnaire (p < 0.05), but on individual level, the result was partly significant. The relation between extension and flexion force in the hand was not correlated, however, after the exercise there was a strong association between flexion and extension force (p < 0.001). The result on individual level is related to age and duration time.

    Conclusion:

    Twelve weeks of hand exercise significantly improved hand strength, hand function and perceived function for RA patients. Furthermore, exercise improved the relation between the finger extension and flexion force. Hand exercise is thus an effective intervention for RA patients, providing better strength and function.

    References:

    1. Brorsson, S., M. Hilliges, et al. (2009). A six-week hand exercise programme improves strength and hand function in patients with rheumatoid arthritis. J Rehabil Med 41(5): 338-42.
    2. O'Brien, A.V., P. Jones, et al. (2006). Conservative hand therapy treatments in rheumatoid arthritis–a randomized controlled trial. Rheumatology (Oxford) 45(5): 577-83.
    3. Ronningen, A. and I. Kjeken (2008). ffect of an intensive hand exercise programme in patients with rheumatoid arthritis. Scand J Occup Ther: 1-11.
    4. Weiss, A. P., D. C. Moore, et al. (2004). Metacarpophalangeal joint mechanics after 3 different silicone arthroplasties. J Hand Surg [Am] 29(5): 796-803.
  • 166.
    Broström, E W
    et al.
    Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Esbjörnsson, A-C
    Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    von Heideken, J
    Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Larsson, P
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Wretenberg, Per
    Region Örebro län. Department of Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Iversen, M
    Department of Physical Therapy, Brigham and Women's Hospital, Northeastern University, Boston MA, United States.
    Change in Gait Deviation Index after anti-tumour necrosis factor-α treatment in individuals with rheumatoid arthritis: a pilot study2013Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 42, nr 5, s. 356-361Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Anti-tumour necrosis factor-alpha (TNF-α) inhibitors provide fast, effective resolution of rheumatoid arthritis (RA) inflammation. In this study we aimed to quantify the impact of TNF-α treatment on gait dynamics.

    METHOD: The sample comprised 16 subjects [11 female, median age 56 (range 48-66) years, median disease duration 9.5 (range 4.6-20.6) years] with RA who met the American College of Rheumatology (ACR) criteria, had lower extremity involvement, did not use walking aids, and had started TNF-α treatment within 1 week of baseline gait analysis. Gait analysis focused on three-dimensional (3D) lower extremity joint kinematics, kinetics, time and distance parameters. The Gait Deviation Index (GDI) and GDI-Kinetic were calculated. Data on gait, disease activity, and physical disability were collected at baseline and at 3.5 months.

    RESULTS: Following treatment with TNF-α, statistically significant improvements were found in disease activity [using the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP); median difference (m(d)) = 2.3, p < 0.01], physical disability [Health Assessment Questionnaire (HAQ) m(d) = 0.4, p < 0.01], and pain during walking [visual analogue scale (VAS) m(d) = 11.0, p < 0.05]. Reductions in gait deviations were noted (GDI m(d) = 3.7, p = 0.04; GDI-Kinetic m(d) = 4.1, p = 0.05) along with reductions in dimensionless time and distance parameters. A moderate to good negative correlation existed between baseline GDI and GDI change scores (r(s) = -0.7, p < 0.01).

    CONCLUSIONS: Treatment with TNF-α improved gait dynamics in adults with RA. Significant gait deviations were, however, still present after treatment. In this study, GDI and GDI-Kinetic scores appeared to be useful outcome measures to quantify changes in gait deviations after this intervention.

  • 167. Burgers, L. E.
    et al.
    Siljehult, Filip
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    ten Brinck, R. M.
    van Steenbergen, H. W.
    Landewe, R. B.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    van der Helm-van Mil, A. H.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Performance of the EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis - a longitudinal study2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 82-82Artikel i tidskrift (Övrigt vetenskapligt)
  • 168. Burgers, Leonie E.
    et al.
    Siljehult, Filip
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    ten Brinck, Robin M.
    van Steenbergen, Hanna W.
    Landewé, Robert B. M.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    van der Helm-van Mil, Annette H. M.
    Validation of the EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis2017Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56, nr 12, s. 2123-2128Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives. Recently a EULAR-taskforce defined arthralgia suspicious for progression to RA, in order to allow inclusion of homogeneous sets of arthralgia patients in clinical studies. This longitudinal study aimed (i) to validate this definition in arthralgia patients in whom rheumatologists felt that imminent RA was more likely than other arthralgias [clinically suspect arthralgia (CSA)], that is, the target population fulfilling the entry criterion, and (ii) to explore the performance in arthralgia patients who were referred to secondary care prior to rheumatological evaluation, hence ignoring the entry criterion. Methods. The definition was assessed in 241 Dutch patients identified with CSA by rheumatologists and 113 patients referred to the Umea university hospital with recent-onset arthralgia in small joints. The external reference was arthritis development < 2 years' follow-up. Results. CSA patients with a positive definition (>= 3/7 parameters present) had an increased risk for developing arthritis compared with definition-negative CSA patients (hazard ratio = 2.1, 95% CI: 0.9, 4.7). The sensitivity was 84% and the positive predictive value 30%. In arthralgia patients in whom the definition was applied before rheumatological evaluation, a positive definition was neither sensitive (10%) nor predictive (positive predictive value 3%). Conclusion. The EULAR definition of arthralgia suspicious for progression to RA is sensitive when used to support the rheumatologist's opinion on imminent RA. This validation study shows that the definition, when used as designed, further homogenizes patients that rheumatologists consider at risk for RA. To arrive at a high specificity, the clinical definition needs to be combined with biomarkers.

  • 169.
    Burkill, Sarah
    et al.
    Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Sweden; Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Sweden.
    Montgomery, Scott
    Örebro universitet, Institutionen för medicinska vetenskaper. Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Sweden; Department of Epidemiology and Public Health, University College London, UK.
    Kockum, Ingrid
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Centre for Molecular Medicine, Karolinska University Hospital Solna, Sweden.
    Piehl, Fredrik
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Centre for Molecular Medicine, Karolinska University Hospital Solna, Sweden.
    Strid, Pernilla
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Centre for Molecular Medicine, Karolinska University Hospital Solna, Sweden.
    Hillert, Jan
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden.
    Alfredsson, Lars
    Institute of Environmental Medicine, Karolinska Institutet, Sweden; Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.
    Olsson, Tomas
    Department of Clinical Neuroscience, Karolinska Institutet, Sweden; Centre for Molecular Medicine, Karolinska University Hospital Solna, Sweden.
    Bahmanyar, Shahram
    Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Sweden; Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Sweden.
    The association between multiple sclerosis and pain medications2019Ingår i: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 160, nr 2, s. 424-432Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patients with multiple sclerosis (MS) are at greater risk of pain than people without the disease; however, the occurrence and characteristics of pain among these patients are incompletely described. We aimed to assess characteristics of pain amongst MS patients using MS patients who were recruited to participate in 3 studies in Sweden (n = 3877) and were matched with individuals without MS (n = 4548) by sex, year of birth, and region of residence. The Prescribed Drugs Register identified prescribed pain medication, overall and restricted to those given 4 or more prescriptions in 1 year to assess chronic pain. Anatomical therapeutic chemical codes classified whether pain was neuropathic, musculoskeletal, or migraine. Cox-proportional hazard models were used to estimate associations. Our findings showed patients with MS were at increased risk of pain treatment, with a hazard ratio (HR) of 2.52 (95% confidence interval 2.38-2.66). The largest magnitude HR was for neuropathic pain (5.73, 5.07-6.47) for which 34.2% (n = 1326) of the MS and 7.15% (n = 325) of the non-MS cohort were prescribed a treatment. The HR for chronic pain treatment was 3.55 (3.27-3.84), indicating an increased effect size relative to any pain treatment. Chronic neuropathic pain showed the largest HR at 7.43 (6.21-8.89). Neuropathic pain was shown to be the primary mechanism leading to increased risk of pain in patients with MS.

  • 170.
    Bybrant, Mara Cerqueiro
    et al.
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Grahnquist, Lena
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Hepatology and Nutrition, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Ortqvist, Eva
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Pediatric Diabetes Clinic, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Andersson, Cecilia
    Department of clinical sciences, Lund University, Skåne University hospital, Malmö, Sweden.
    Forsander, Gun
    The Queen Silvia Children’s hospital, Sahlgrenska University hospital and The Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Elding Larsson, Helena
    Department of clinical sciences, Lund University, Skåne University hospital, Malmö, Sweden.
    Lernmark, Ake
    Department of clinical sciences, Lund University, Skåne University hospital, Malmö, Sweden.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Marcus, Claude
    Division of Pediatrics, Department of Clinical Science, Intervention and Technology Karolinska Institutet, Stockholm, Sweden.
    Carlsson, Annelie
    Department of Pediatrics, Lund University, Lund, Sweden.
    Ivarsson, Sten A.
    Department of clinical sciences, Lund University, Skåne University hospital, Malmö, Sweden.
    Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study2018Ingår i: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 51, nr 5, s. 221-227Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).

    Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18 years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).

    Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p = .00001) and those with DQX/X (p ≤ .00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p = .018).

    Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.

  • 171. Camitz, M.
    et al.
    Liljeros, F.
    Travel restrictions for moderately contagious diseases2011Ingår i: Hospitality and Health: Issues and Developments, Apple Academic Press , 2011, s. 95-105Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    Much research in epidemiology has been focused on evaluating conventional methods of control strategies in the event of an epidemic or pandemic. Travel restrictions are often suggested as an efficient way to reduce the spread of a contagious disease that threatens public health, but few chapters have studied in depth the effects of travel restrictions. In this study, we investigated what effect different levels of travel restrictions might have on the speed and geographical spread of an outbreak of a disease similar to severe acute respiratory syndrome (SARS). 

  • 172.
    Carlberg, Konstantin
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Vickovic, Sanja
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ståhl, Patrik
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Salmén, Fredrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Korotkova, Marina
    Malmstrom, Vivianne
    Lundeberg, Joakim
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    TRANSCRIPTOME VISUALISATION OF THE INFLAMED RHEUMATOID ARTHRITIS JOINT2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. A58-A59Artikel i tidskrift (Refereegranskat)
  • 173. Carli, C.
    et al.
    Ehlin, A. G. C.
    Klareskog, L.
    Lindblad, S.
    Montgomery, Scott M.
    Örebro universitet, Institutionen för klinisk medicin.
    Trends in disease modifying antirheumatic drug prescription in early rheumatoid arthritis are influenced more by hospital setting than patient or disease characteristics2006Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 65, nr 8, s. 1102-1105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To characterise temporal trends and factors associated with the prescription of disease modifying antirheumatic drugs (DMARDs) at the initial consultation in early rheumatoid arthritis (RA).

    Methods: Data from 2584 patients with early RA at 19 hospitals were extracted from the Swedish Rheumatoid Arthritis Register for the period 1997–2001. Disease characteristics and DMARD prescription at first consultation with the rheumatologist were investigated using cross tabulation and logistic regression.

    Results: DMARD prescriptions, particularly for methotrexate, increased from 1997 to 2001 independently of patient characteristics. Stratification by hospital type showed that patients in district hospitals were less likely to be prescribed DMARDs than those in university hospitals (adjusted odds ratio (OR) = 0.53 (95% confidence interval (CI) 0.40 to 0.69), p<0.001), independently of confounding factors. Association of the DAS28 with the likelihood of DMARD prescription was greater among patients attending district hospitals (OR = 1.65 (1.34 to 2.02), p<0.001) than those at university hospitals (OR = 1.23 (1.07 to 1.41), p = 0.003) and county hospitals (OR = 1.34 (1.01 to 1.63), p = 0.003). Interaction testing indicated that the difference was significant (p = 0.007).

    Conclusions: Temporal trends in DMARD prescription indicate an increasingly aggressive approach to disease management among Swedish rheumatologists. However, the association of hospital type with DMARD prescription suggests that the adoption of research findings in clinical care varies considerably.

  • 174. Carli, Cheryl
    Charting the possible impact of national guidelines on the management of rheumatoid arthritis.2008Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, ISSN 0300-9742, Vol. 37, nr 3, s. 188-193Artikel i tidskrift (Refereegranskat)
  • 175.
    Carlsson Almlöf, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Alexsson, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Imgenberg-Kreuz, Juliana
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Sylwan, Lina
    Karolinska Inst, Dept Biosci & Nutr, Sci Life Lab SciLifeLab, Solna, Sweden..
    Bäcklin, Christofer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tandre, Karolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Padyukov, Leonid
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Bengtsson, Christine
    Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden..
    Jonsen, Andreas
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Dahlqvist, Solbritt Rantapaa
    Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden..
    Sjowall, Christopher
    Linkoping Univ, Dept Clin & Expt Med, AIR Rheumatol, Linkoping, Sweden..
    Bengtsson, Anders A.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Novel risk genes for systemic lupus erythematosus predicted by random forest classification2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 6236Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual's SLE risk we designed a random forest classifier using SNP genotype data generated on the "Immunochip" from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.

  • 176. Cedstromer, Anna-Lena
    et al.
    Ahlqwist, Margareta
    Andlin-Sobocki, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Käkkirurgi.
    Berntson, Lillemor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Hedenberg-Magnusson, Britt
    Dahlstrom, Lars
    Temporomandibular condylar alterations in juvenile idiopathic arthritis most common in longitudinally severe disease despite medical treatment2014Ingår i: Pediatric Rheumatology, ISSN 1546-0096, E-ISSN 1546-0096, Vol. 12, s. 43-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Juvenile idiopathic arthritis (JIA) is an autoimmune, heterogeneous disease and the temporomandibular joint (TMJ) can be affected, with consequences for mandibular growth and function. The aim of this study was to evaluate the importance of longitudinal medical treatment and the burden of disease activity on the development of temporomandibular condylar alterations as judged on panoramic radiographs. Methods: The study was a retrospective evaluation of dental and medical records in consecutive JIA patients referred to three specialist dental clinics in Sweden during an eight-year period. Data on the total pharmacological treatment and disease activity were evaluated longitudinally from disease onset to the time of the panoramic examination, during a median observation period of 2.5 years. The radiographs were analysed in terms of structural and shape alterations in the condyles and judged dichotomously. Results: Panoramic examinations were analysed in 158 patients from 266 referrals diagnosed with JIA. Condylar alterations (shape or structural) were seen in 68 patients (43%). Patients with condylar alterations were more extensively treated over time compared with those without condylar alterations. Powerful disease activity and/or potent medication at any time during the course of the disease implied an increased risk of alterations. Conclusions: Patients with JIA who require more intensive medication over time run the greatest risk of condylar alterations. As yet, current medical programmes have not been specified for the TMJ and more knowledge in this area is needed.

  • 177.
    Cerqueira, C. Fernandes
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Sohrabian, Azita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Albrecht, I.
    Karolinska Inst, Karolinska Univ Hosp, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Notarnicola, A.
    Karolinska Inst, Karolinska Univ Hosp, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Ossipova, E.
    Karolinska Inst, Karolinska Univ Hosp, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Lengqvist, J.
    Karolinska Inst, Karolinska Univ Hosp, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Fati, M.
    Karolinska Inst, Resp Med Unit, Dept Med, Karolinska Univ Hosp, Stockholm, Sweden..
    Pruijn, G. J.
    Radboud Univ Nijmegen, Dept Biomol Chem, Radboud Inst Mol Life Sci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Inst Mol & Mat, Nijmegen, Netherlands..
    Grunewald, J.
    Karolinska Inst, Resp Med Unit, Dept Med, Karolinska Univ Hosp, Stockholm, Sweden..
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Lundberg, I. E.
    Karolinska Inst, Karolinska Univ Hosp, Rheumatol Unit, Dept Med, Stockholm, Sweden..
    Jakobsson, P. -J
    Characterization of Extracellular Histidyl-TRNA Synthetase in Myositis2016Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, s. 736-737Artikel i tidskrift (Övrigt vetenskapligt)
  • 178.
    Chalise, Jaya Prakash
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Immune tolerance by interferon-alpha in experimental arthritis2015Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Type I Interferons (mainly IFN-α & IFN-β) belong to a family of cytokines that possess strong antiviral and immunomodulatory properties. Pro- and/or anti-inflammatory effects of type I IFN have been observed in infectious diseases and several autoimmune diseases including SLE, MS, RA and experimental models thereof, but what defines either outcome is largely obscure. The main aim of this thesis is to understand how IFN-α may act anti-inflammatory in a model of antigen-induced arthritis (AIA). In this model, mice are sensitised with methylated-BSA (mBSA) emulsified in Freund’s adjuvant at day 1 and 7 followed by intra-articular injection of mBSA in the knee joint at day 21, which induces arthritis within 1 week.

    Administration of IFN-α at the time of mBSA sensitisations (day 1 and day 7) but not at induction of arthritis (day 21) clearly protected against arthritis in a type I IFN receptor dependent manner. Humoral immunity might not be involved in this protection as the levels of antigen-specific IgG (total, IgG1, IgG2a and IgG2b), IgA, IgE in serum were not altered in IFN-α treated mice. However, IFN-α-protection was accompanied by delayed and decreased antigen-specific proliferative responses in spleen and lymph node cells ex vivo, including impaired proliferative recall responses after intra-articular antigenic challenge.

    In the course of AIA, IFN-α inhibited the increase of circulatory IL-6, IL-10, IL-12, and TNF in the sensitisation phase (day 0-21) and also the re-call response of IL-1β, IL-10, IL-12, TNF, IFN-γ, and IL-17 induced by intra-articular mBSA challenge in arthritis phase (day 21-28). This IFN-α-inhibition of cytokines was also apparent in mBSA-re-stimulated spleen and lymph node cell cultures ex vivo, including inhibited cytokine production in CD4+ T helper cells and macrophages. In contrast to the inhibition of pro-inflammatory cytokines, the levels of immunomodulatory TGF-β was clearly enhanced in IFN-α-treated mice, both in serum and in re-stimulated leucocytes cultures including both macrophages, especially in the sensitisation phase, and in CD4+ T cells in the arthritis phase. By  inhibiting TGF-β signalling in vivo, the protective effect of IFN-α was  shown to be dependent on TGF-β signalling in the sensitisation phase.

    The cytokine TGF-β is an activator of the indoleamine 2,3 dioxygnese (IDO1), a potent immuneregulatory component that acts via enzymatic production of kynurenine (Kyn) and signalling activity. The IFN-α-protective effect in AIA was associated with both increased expression and enzymatic activity of IDO1 and the IFN-α-protection was totally ablated in mice lacking IDO1 expression (IDO1 KO mice) and in mice treated with the inhibitor of the enzymatic activity of IDO1 (1-Methyl Tryptophan; 1-MT). Interestingly, administration of the IDO-metabolite Kyn protected mice from AIA in an IFNARindependent manner. These observations show that the IDO1 enzymatic activity is important for the protective effect of IFN-α. Using 1-MT, it was further shown that the enzymatic activity of IDO1 was, like TGF-β, crucial only at the sensitisation but not in the arthritis phase of AIA for IFN-α to protect against arthritis. Instead, IDO1’s non-enzymatic signalling activity, characterized by sustained expression of IDO1 and non-canonical NF-κB activation in pDCs, was observed in the arthritis phase in spleen cells from mice treated with IFN-α.

    Regulatory T cells (Treg cells) were also found to be important for IFN-α-protection in AIA. Transient depletion of Treg cells by diphtheria toxin in DEREG mice in the arthritis phase, but not during the sensitisation phase abolished IFN-α-protection. Treatment with IFN-α enhanced the numbers of Treg cells in the course of AIA and their function; compared to untreated mice, Treg cells isolated at day 10 and 20 of AIA from IFN-α- treated mice exhibited higher suppressive activity against mBSA-stimulated proliferation of responder T cells. The enhancing effect of IFN-α on Treg cell numbers was observed in blood, spleen, LNs and also in ex-vivo cultures of leucocytes re-stimulated with mBSA and IFN-α. Although IFN-α clearly increased the suppressive activity of Treg cells, adoptive transfer of Treg cells from mBSA immunized mice, regardless of IFN-α treatment, prevented the development of arthritis.

    Conclusion

    In the presence of IFN-α during antigen sensitisation, a state of tolerance is established, which is able to prevent joint inflammation induced by antigenic re-challenge. This immunological tolerance is created in the sensitisation phase of AIA and is characterized by inhibition of pro-inflammatory cytokines, increased TGF-β production and activity of the IDO1 enzyme, the latter two being indispensable for IFN-α-induced protection. Administration of Kyn, the metabolite of the enzymatic activity of IDO1, in the sensitisation phase also protected against AIA downstream of type I IFN signalling. In the arthritis phase regulatory T cells, whose numbers and suppressive capacity was clearly enhanced by IFN-α, mediate the actual prevention of arthritis development in IFN-α-treated animals. We have thus identified molecular and cellular components of the anti-inflammatory program elicited by IFN-α including Kyn that may not have the pro-inflammatory effects associated with IFN.

  • 179.
    Chalise, Jaya Prakash
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Chenna Narendra, Sudeep
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Biggs, Sophie
    Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Kalinke, Ulrich
    Twincore, Germany.
    Iacono, Alberta
    Department of Experimental Medicine, University of Perugia, Perugia, Italy.
    Boon, Louis
    EPIRUS Biopharmaceuticals, Utrecht, Netherlands.
    Magnusson, Mattias
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Regulatory T cells manifest IFN-α mediated protection during antigen induced arthritisManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Introduction

    Type I interferon induces tolerance against arthritogenic antigen and protects against antigen induced arthritis (AIA). Regulatory T cells (Treg cells) resolve aberrant immune reaction, maintain self-tolerance and prevent the development of autoimmune diseases. We here investigated the impact of Interferon alpha (IFN-α) on Treg cells development and function during antigen induced arthritis.

    Methods

    For AIA, mice were immunized with methylated bovine serum albumin (mBSA) at day 1 and 7 in presence or absence of IFN-α. At day 21, arthritis was induced by intra-articular injection of mBSA and arthritis was evaluated at day 28. At various days of AIA, CD4, CD25, Foxp3 and CTLA-4 expression was quantified by FACS in blood cells, splenocytes, lymph nodes cells and in ex vivo re-stimulated leucocytes (pooled splenocytes and lymph nodes cells) isolated at same days. To investigate the importance of Treg cells in IFN-α protection in AIA, Foxp3DTReGFP+mice were used, where Treg cells can be depleted transiently by administration of diptherin toxin. CFSE based suppression assay was used to assess the suppression by Treg cells isolated day 4, 10, 20 of AIA against proliferation of mBSA or anti-CD3 stimulated responder T cells (Tresp cells) isolated at same days. For adoptive transfer experiments, 250,000 Treg cells from IFN-α treated or untreated mice day 20 of AIA were intravenously injected to recipient pre-immunized mice without IFN-α treatment during the induction of arthritis. The importance of IFN-α signalling on T cells for the IFN-α protection was evaluated by using CD4-Cre+/- IFNAR flox/flox mice.

    Results

    Protective effects of IFN-α in AIA were associated with significant TGF-β dependent increase in Foxp3+ T cells in blood at day 4 and minor increase of Foxp3+T cells in spleen and lymph node cells. However IFN-α signalling in T cells is not required for IFN-α-protection. Upon ex vivo re-stimulation in presence of IFN-α with mBSA but not anti-CD3, the Treg cells numbers were increased in leucocytes isolated from day 4 and day 10 of AIA. Transient depletion of Treg cells during induction of arthritis (day 21) abolished IFN-α-protection however the protection was not affected when Treg cells are depleted during immunization phase (day 1 and day 7). Against mBSA-stimulated proliferation of Tresp cells, suppression by Treg cells isolated from day 10 and day 20 from IFN-α treated mice are significantly higher than Treg cells from untreated mice. Treg cells isolated from IFN-α or untreated mice at day 20 of AIA when transferred to pre-immunized untreated mice prevent the development of arthritis.

    Conclusion

    Treg cells are critically associated with IFN-α protective effects in AIA. IFN-α enhances TGF-β dependent early development of Treg cells and later IFN-α enhances their suppressive capacity against T cells proliferation in antigen specific manner during AIA.

  • 180.
    Chalise, Jaya Prakash
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Pallotta, Maria Teresa
    Department of Experimental Medicine, University of Perugia, Perugia, Italy.
    Chenna Narendra, Sudeep
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Carlsson, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Iacono, Alberta
    Department of Experimental Medicine, University of Perugia, Perugia, Italy.
    Boon, Louis
    EPIRUS Biopharmaceuticals, Utrecht, Netherlands.
    Grohmann, Ursula
    Department of Experimental Medicine, University of Perugia, Perugia, Italy.
    Magnusson, Mattias
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    IDO1 and TGF- 1 β mediate protective effects of IFN-α in antigen-induced arthritisManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Interferon-α (IFN-α) prevents antigen-induced arthritis (AIA) in mice by an unknown mechanism. Indoleamine 2, 3 dioxygenase 1 (IDO1) is an immunoregulator via enzymatic as well as signalling activity, which can be activated by TGF-β and further mediated via non canonical NF-κB signalling. We here investigated whether IDO1 and TGF-β are involved in IFN-α protective effects in AIA. Arthritis was induced in wt, Ido1-/- or Ifnar-/- mice, treated or not with IFN-α or kynurenine, the main IDO1 product, and antibodies neutralizing TGF-β or 1-methyltryptophan (1-MT), an inhibitor of IDO1 catalytic activity. IDO1 expression and enzymatic activity were determined by RT-PCR and HPLC, respectively. Proliferation was measured by 3H-Thymidine incorporation. Non-canonical NF-κB signalling was evaluated by ELISA and Western blot in plasmacytoid DCs (pDCs) from treated mice. Protective effects of IFN-α in AIA were associated with increased IDO1 expression and kynurenine production in spleen cells, particularly at the time of mBSA sensitization. Lack of IDO1 ablated IFN-α protection and kynurenine prevented AIA in an IFNAR-independent manner. The IDO1 catalytic activity was crucial for IFN-α effects at the sensitization but not effector phase of AIA. The disease effector phase in mice treated with IFN-α was instead characterized by sustained IDO1 and TGF-β expression and activation of the noncanonical NF-κB pathway in pDCs. IFN-α protective effects in AIA involves IDO1 enzymatic and signalling activity in the disease sensitization and effector phase, respectively. Kynurenine, the main IDO1 metabolite, can be used as an alternative treatment to IFN-α in protecting mice from AIA.

  • 181. Chatzidionysiou, K
    et al.
    Kristensen, L-E
    Eriksson, J
    Askling, J
    van Vollenhoven, R
    Effectiveness and survival-on-drug of certolizumab pegol in rheumatoid arthritis in clinical practice: results from the national Swedish register2015Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, nr 6, s. 431-437Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Evidence regarding the efficacy and effectiveness of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients who have failed to respond to treatment with a tumour necrosis factor inhibitor (TNFi) is limited. The aim of this study was to describe the effectiveness and survival-on-drug of CZP in a real-life setting, both in TNFi-naïve patients and in patients who had previously failed TNFis, and in relation to disease activity at baseline.

    METHOD: The national Swedish Rheumatology Quality Register (SRQ) was used to identify patients with RA starting treatment with CZP between 2009 and 2013. The effectiveness of treatment was assessed using the 28-joint Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), measures of remission, the European League Against Rheumatism (EULAR) response during 0-6 months from start of treatment, and survival-on-drug during the first 30 months.

    RESULTS: A total of 945 RA patients started treatment with CZP. Of these, 540 (57.1%) received CZP as the first biological treatment, 215 (23%) had failed one previous TNFi, and 190 (20%) had failed at least two TNFis. Overall, 71% achieved at least a EULAR moderate response and 38% had a EULAR good response at 6 months from baseline. TNFi-naïve patients achieved significantly better results and had better survival-on-drug compared to patients who had failed previous TNFis. Around 20% of patients who had not responded to two or more prior TNFis achieved EULAR good response to therapy and a similar percentage achieved remission. Patients who had high baseline disease activity had a higher risk of discontinuing treatment compared to those without high disease activity.

    CONCLUSIONS: In this real-life RA cohort, CZP was associated with significant clinical improvement. The effectiveness and survival-on-drug vary markedly depending on the line of treatment.

  • 182. Checa, A.
    et al.
    Idborg, H.
    Zandian, A.
    Sar, D. Garcia
    Surowiec, Izabella
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Svenungsson, E.
    Jakobsson, P-J
    Nilsson, P.
    Gunnarsson, I.
    Wheelock, C. E.
    Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study2017Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 26, nr 10, s. 1023-1033Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus.

    Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease.

    Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C-16:0-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C-16:0-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C-16:0- and C-24:1-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment.

    Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.

  • 183. Checa, A.
    et al.
    Idborg, H.
    Zandian, Arash
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sar, D. Garcia
    Surowiec, I.
    Trygg, J.
    Svenungsson, E.
    Jakobsson, P-J
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Gunnarsson, I.
    Wheelock, C. E.
    Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study2017Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 26, nr 10, s. 1023-1033Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C-16:0-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C-16:0-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C-16:0- and C-24:1-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.

  • 184. Checa, C. Magro
    et al.
    Zirkzee, E. J. M.
    Beaart, H. J. L.
    Sohrabian, Azita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Trouw, L. A.
    Huizinga, T. W. J.
    Steup-Beekman, G. M.
    Cluster Analysis of an ARRAY of Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus (NPSLE)2014Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, s. 532-533Artikel i tidskrift (Övrigt vetenskapligt)
  • 185.
    Chemin, Karine
    et al.
    Karolinska Inst, Rheumatol Unit, Dept Med, Med, Stockholm, Sweden..
    Pollastro, Sabrina
    Dept Clin Immunol & Rheumatol, Amsterdam, Netherlands..
    James, Eddie
    Virginia Mason, Benaroya Res Inst, Seattle, WA USA..
    Ge, Changrong
    Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, Stockholm, Sweden..
    Albrecht, Inka
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Herrath, Jessica
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gerstner, Christina
    Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Rizzi, Thais
    Dept Clin Immunol & Rheumatol, Amsterdam, Netherlands..
    Tandre, Karolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Catrina, Anca I.
    Karolinska Inst, Dept Med Solna, Unit Rheumatol, Karolinska Univ Hosp, Stockholm, Sweden..
    Holmdahl, Rikard
    Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden..
    Klareskog, L.
    Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    De Vries, Niek
    Univ Amsterdam, Acad Med Ctr, Dept Clin Immunol & Rheumatol, Amsterdam Rheumatol & Immunol Ctr, NL-1105 AZ Amsterdam, Netherlands..
    Malmstrom, Vivianne
    Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    A Novel HLA-DRB1*10:01 Restricted T Cell Epitope from Citrullinated Type II Collagen Relevant for Rheumatoid Arthritis2015Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, nr Suppl. 10, artikel-id 1946Artikel i tidskrift (Övrigt vetenskapligt)
  • 186.
    Chemin, Karine
    et al.
    Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Pollastro, Sabrina
    Amsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands..
    James, Eddie
    Virginia Mason, Benaroya Res Inst, Seattle, WA USA..
    Ge, Changrong
    Karolinska Inst, Stockholm, Sweden..
    Albrecht, Inka
    Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Herrath, Jessica
    Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Gerstner, Christina
    Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Tandre, Karolina
    Rizzi, Thais Sampaio
    Amsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands..
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Catrina, Anca
    Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Holmdahl, Rikard
    Karolinska Inst, Stockholm, Sweden..
    Klareskog, Lars
    Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    de Vries, Niek
    Amsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands..
    Malmstrom, Vivianne
    Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    A Novel HLA-DRB1*10:01-Restricted T Cell Epitope From Citrullinated Type II Collagen Relevant to Rheumatoid Arthritis2016Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 68, nr 5, s. 1124-1135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Antibodies against citrullinated type II collagen (Cit-CII) are common in the sera and synovial fluid of patients with rheumatoid arthritis (RA); however, the known T cell epitope of CII is not dependent on citrullination. The aim of this study was to identify and functionally characterize the Cit-CII-restricted T cell epitopes that are relevant to RA. Methods. Peripheral blood mononuclear cells (PBMCs) from HLA-DRB1*10:01-positive patients with RA and healthy donors were stimulated in vitro with candidate CII peptides. CD154 up-regulation was measured as a marker of antigen-specific activation, and anti-HLA-DR-blocking experiments confirmed HLA restriction. Cytokine production was measured using a Luminex technique. Direct peptide-binding assays using HLA-DRB1*10:01 and HLA-DRB1*04:01 monomeric proteins were performed. The T cell receptor (TCR) beta-chain of CD154-enriched antigen-specific T cells was analyzed using high-throughput sequencing. Results. A novel Cit-CII peptide was identified based on its ability to activate CD4+ T cells from HLA-DRB1*10:01-positive individuals. When stimulated in vitro, Cit-CII autoreactive T cells produced proinflammatory cytokines. Cit-CII311-325 bound (with low affinity) to HLA-DRB1*10:01 but not to HLA-DRB1*04:01, while the native form was unable to bind either protein. In addition, highly expanded clones were identified in the TCR beta repertoire of Cit-CII311-325-stimulated PBMCs. Conclusion. These results illustrate the ability of the citrullination process to create T cell epitopes from CII, a cartilage-restricted protein that is relevant to RA pathogenesis. The exclusive binding of Cit-CII311-325 to HLA-DRB1*10:01 suggests that recognition of citrullinated epitopes might vary between individuals carrying different RA-associated HLA-DR molecules.

  • 187.
    Chemin, Karine
    et al.
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
    Ramsköld, Daniel
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
    Diaz-Gallo, Lina-Marcela
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
    Herrath, Jessica
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
    Houtman, Miranda
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
    Tandre, Karolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Catrina, Anca
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
    Malmström, Vivianne
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
    EOMES-positive CD4+ T cells are increased in PTPN22 (1858T) risk allele carriers.2018Ingår i: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 48, nr 4, s. 655-669Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The presence of the PTPN22 risk allele (1858T) is associated with several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk allele on T-cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR-activation, naïve human CD4+ T cells homozygous for the PTPN22 risk allele overexpress a set of genes including CFLAR and 4-1BB, which are important for cytotoxic T-cell differentiation. Moreover, the protein expression of the T-box transcription factor Eomesodermin (EOMES) was increased in T cells from healthy donors homozygous for the PTPN22 risk allele and correlated with a decreased number of naïve CD4+ T cells. There was no difference in the frequency of other CD4+ T cell subsets (Th1, Th17, Tfh, Treg). Finally, an accumulation of EOMES+CD4+ T cells was observed in synovial fluid of RA patients with a more pronounced production of Perforin-1 in PTPN22 risk allele carriers. Altogether, we propose a novel mechanism of action of PTPN22 risk allele through the generation of cytotoxic CD4+ T cells and identify EOMES+CD4+ T cells as a relevant T-cell subset in RA pathogenesis.

  • 188.
    Chenna Narendra, Sudeep
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Systemic and local regulation of experimental arthritis by IFN-α, dendritic cells and uridine2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    In this thesis, we have studied the immunological processes of joint inflammation that may be targets for future treatment of patients with arthritis. We focus on the immune-modulating properties of interferon-α (IFN-α) and uridine in experimental arthritis. The nucleoside uridine, which is regarded a safe treatment has anti-inflammatory properties notably by inhibiting tumor necrosis factor (TNF) release. Because the inflamed synovium in rheumatoid arthritis (RA) is characterised by pathogenic TNF-production, uridine could potentially be away to ameliorate arthritis. Systemic administration of uridine had no effect on antigeninduced arthritis (AIA), which is a T-cell dependent model where animals are immunized twice (sensitization) with bovine serum albumin (mBSA), before local triggering of arthritis by intra-articular antigen (mBSA) re-challenge. In contrast, intra-articular administration of uridine clearly down modulated development of AIA in a dose dependent manner and inhibited the expression of synovial adhesion molecules, influx of inflammatory leukocytes and synovial expression of TNF and interleukin 6, but did not affect systemic levels of proinflammatory cytokines or antigen-specific T-cell responses. Local administration of uridine may thus be a viable therapeutic option for treatment of arthritis in the future.

    Viral double-stranded deoxyribonucleic acid (dsRNA), a common nucleic acid found in most viruses, can be found in the joints of RA patients and local deposition of such viral dsRNA induces arthritis by activating IFN-α. Here we show that arthritis induced by dsRNA can be mediated by IFN-producing dendritic cells in the joint and this may thus explain why viral infections are sometimes associated with arthritis.

    Earlier, to study the effect of dsRNA and IFN-α in an arthritis model, that like RA, is dependent on adaptive immunity, dsRNA and IFN-α were administered individually during the development of AIA. Both molecules clearly protected against AIA in a type I IFN receptor-dependent manner but were only effective if administered in the sensitization phase of AIA. Here we show that the anti-inflammatory effect of IFN-α is critically dependent on signalling via transforming growth factor β (TGF-β) and the enzymatic activity of indoleamine 2,3 dioxygenase 1 (IDO). The IDO enzyme is produced by plasmacytoid DC and this cell type was critically required both during antigen sensitization and in the arthritis phase of AIA for the protective effect of IFN-α against AIA. In contrast, TGF-β and the enzymatic activity of IDO were only required during sensitization, which indicate that they are involved in initial steps of tolerogenic antigen sensitization. In this scenario, IFN- α first activates the enzymatic activity of IDO in pDC, which converts Tryptophan to Kynurenine, which thereafter activates TGF-β. Common for IDO-expressing pDC, Kyn and TGF-β is their ability to induce development of regulatory T cells (Tregs). We found that Tregs were crucial for IFN-α-mediated protection against AIA, but only in the arthritis phase. In line with this, adoptive transfer of Tregs isolated from IFN-α treated mice to recipient animals in the arthritis phase clearly protected against AIA. The numbers of Tregs were not significantly altered by IFN-α but IFN-α increased the suppressive capacity of Tregs against antigen-induced proliferation. This enhanced suppressive activity of Tregs in the arthritis phase was dependent on the earlier activated enzyme IDO1 during the sensitization phase of AIA. Thus, presence of IFN-α at the time of antigen sensitization activates the enzymatic activity of IDO, which generates Tregs with enhanced suppressive capacity that upon antigen re-challenge prevents inflammation. We have thus identified one example of how immune tolerance can be developed, that may be a future way to combat autoimmunity.

  • 189.
    Christensson, Marta
    et al.
    Department of Clinical Immunology, Karolinska Institutet, Huddinge.
    Pettersson, Erna
    Department of Renal Medicine, Karolinska Institutet, Huddinge University.
    Eneslätt, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Christensson, Birger
    Department of Clinical Immunology, Karolinska Institutet, Huddinge.
    Bratt, Johan
    Department of Rheumatology, Karolinska Institutet, Huddinge University.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sundqvist, Karl-Gösta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Serum sFAS levels are elevated in ANCA-positive vasculitis compared with other autoimmune diseases2002Ingår i: Journal of Clinical Immunology, ISSN 0271-9142, E-ISSN 1573-2592, Vol. 22, nr 4, s. 220-227Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of the Fas/FasL system in ANCA-associated vasculitis is unclear. We therefore assessed levels of soluble Fas (sFas) in sera and Fas expression on mononuclear cells from patients with ANCA-positive vasculitis and compared the results with those found in other rheumatic diseases. Serum levels of sFas were determined by ELISA. The ANCA-positive vasculitis patients studied included 29 at onset, 17 in first remission while on therapy, and 12 in quiescence. For comparison, 10 patients with Sjogren’s syndrome (SS), 14 patients with systemic lupus erythematosus (SLE), 29 patients with rheumatoid arthritis (RA), 7 patients on dialysis (DP), and 26 healthy controls (HC) were studied. In addition, Fas expression in mononuclear cells was examined at the mRNA level using reverse transcriptase (RT)-PCR in 6 vasculitis patients at onset and in first remission. The expression of CD95 on the surface of leukocytes was determined by flow cytometry in 6 vasculitis patients at onset of the disease, in 6 patients in clinical remission, and in 6 HC. Expression of Fas and FasL in renal biopsy specimens was studied using immunohistochemistry. Patients with vasculitis had high sFas levels irrespective of disease phase. Both vasculitis patients and patients with RA and SLE had significantly increased sFas levels compared with healthy controls. All patient groups had sFas levels, which correlated with raised serum creatinine values. However, the sFas levels in vasculitis patients in first remission and in quiescence were increased despite a lower serum creatinine compared with onset. Some of the vasculitis patients showed an increased mRNA expression of Fas in mononuclear cells after treatment, suggesting that Fas production fluctuates with the intensity of the disease. The expression of CD95 on leukocytes was slightly decreased in vasculitis patients compared to healthy controls. No alterations of Fas and FasL expression were seen in renal biopsy specimens. These results show that ANCA-positive vasculitis patients have high sFas levels and that the levels remain elevated even in clinical remission. The findings indicate that perturbations in the Fas/Fas ligand system may play a role in the disease process in ANCA vasculitis.

  • 190.
    Cloutier, Basile Tessier
    et al.
    McGill Univ, Clin Epidemiol, Montreal, PQ, Canada..
    Farinha, Pedro
    British Columbia Canc Agcy, Pathol, Vancouver, BC V5Z 4E6, Canada..
    Bernatsky, Sasha
    McGill MUHC RVH, Rheum Clin Epid, Montreal, PQ, Canada..
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Clarke, Ann E.
    Montreal Gen Hosp, Immunol Epidemiol, Montreal, PQ H3G 1A4, Canada..
    Ramsey-Goldman, Rosalind
    SLICC, Chicago, IL USA..
    Gascoyne, Randy
    Univ British Columbia, BC Canc Agcy, Pathol, Vancouver, BC V5Z 1M9, Canada..
    Cell of Origin of Diffuse Large B-Cell Lymphoma (DLBCL) in Patients with Systemic Lupus Erythematosus (SLE)2015Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, nr Suppl. 10, artikel-id 719Artikel i tidskrift (Övrigt vetenskapligt)
  • 191. Cobb, Joanna E.
    et al.
    Plant, Darren
    Flynn, Edward
    Tadjeddine, Meriem
    Dieude, Philippe
    Cornelis, Francois
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Goulielmos, George
    Boumpas, Dimitrios T.
    Sidiropoulos, Prodromos
    Krintel, Sophine B.
    Ornbjerg, Lykke M.
    Hetland, Merete L.
    Klareskog, Lars
    Haeupl, Thomas
    Filer, Andrew
    Buckley, Christopher D.
    Raza, Karim
    Witte, Torsten
    Schmidt, Reinhold E.
    FitzGerald, Oliver
    Veale, Douglas
    Eyre, Stephen
    Worthington, Jane
    Identification of the Tyrosine-Protein Phosphatase Non-Receptor Type 2 as a Rheumatoid Arthritis Susceptibility Locus in Europeans2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 6, s. e66456-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA). However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA.

    Methods: A cohort of 4286 RA patients from across Europe and 5642 population matched controls were genotyped for 25 SNPs, then combined in a meta-analysis with previously published data.

    Results: Significant evidence of association was detected for nine SNPs within the European samples. When meta-analysed with previously published data, 21 SNPs were associated with RA susceptibility. Although SNPs in the PTPN2 gene were previously reported to be associated with RA in both Japanese and European populations, we show genome-wide evidence for a different SNP within this gene associated with RA susceptibility in an independent European population (rs7234029, P = 4.4x10(-9)).

    Conclusions: This study provides further genome-wide evidence for the association of the PTPN2 locus (encoding the T cell protein tyrosine phosphastase) with Caucasian RA susceptibility. This finding adds to the growing evidence for PTPN2 being a pan-autoimmune susceptibility gene.

  • 192.
    Crema, M. D.
    et al.
    Boston Univ, Sch Med, Dept Radiol, Quantitat Imaging Ctr, 820 Harrison Ave,FGH Bldg,3rd Floor, Boston, MA 02118 USA.;Univ Paris 06, St Antoine Hosp, Dept Radiol, Paris, France..
    Roemer, F. W.
    Boston Univ, Sch Med, Dept Radiol, Quantitat Imaging Ctr, 820 Harrison Ave,FGH Bldg,3rd Floor, Boston, MA 02118 USA.;Univ Erlangen Nurnberg, Dept Radiol, Erlangen, Germany..
    Li, L.
    Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA..
    Alexander, R. C.
    Pfizer Neurosci, Cambridge, MA USA.;AstraZeneca, London, England..
    Chessell, I. P.
    Boston Univ, Sch Med, Dept Radiol, Quantitat Imaging Ctr, 820 Harrison Ave,FGH Bldg,3rd Floor, Boston, MA 02118 USA.;AZ Neuro, Cambridge, England..
    Dudley, A. D.
    Boston Univ, Sch Med, Dept Radiol, Quantitat Imaging Ctr, 820 Harrison Ave,FGH Bldg,3rd Floor, Boston, MA 02118 USA.;AZ Neuro, Cambridge, England..
    Karlsten, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. AstraZeneca, London, England..
    Rosen, L. B.
    Flex Pharma, Boston, MA USA.;AstraZeneca, London, England..
    Guermazi, A.
    Boston Univ, Sch Med, Dept Radiol, Quantitat Imaging Ctr, 820 Harrison Ave,FGH Bldg,3rd Floor, Boston, MA 02118 USA..
    Comparison between semiquantitative and quantitative methods for the assessment of knee synovitis in osteoarthritis using non-enhanced and gadolinium-enhanced MRI2017Ingår i: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 25, nr 2, s. 267-271Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To compare different semiquantitative and quantitative methods using both non-enhanced and gadolinium-enhanced MRI techniques for the assessment of synovitis in knee osteoarthritis (OA). Methods: Knees with end-stage clinical OA in patients undergoing total knee replacement surgery were included in this cross-sectional study. MRI was performed on all knees. Standard non-enhanced and gadolinium-enhanced sequences were acquired. Using non-enhanced MRI, we semiquantitatively assessed two features widely used as surrogates for synovitis: effusion-synovitis and Hoffa-synovitis. Using gadolinium-enhanced sequences, we semiquantitatively assessed synovial thickness. We quantitatively evaluated the total synovial volume on the gadolinium-enhanced sequences as well. We assessed the correlations of effusion-synovitis and Hoffa-synovitis with synovial thickness and volume, applying Spearman correlation analysis. The diagnostic performance of both synovitis features on non-enhanced MRI was assessed using synovial thickness on gadolinium-enhanced MRI as the reference. Results: A total of 104 subjects (one knee per subject) were included. Correlations of effusion-synovitis with synovial thickness and volume were r = 0.41 and r = 0.43 (P < .001) r = 0.32 and r = 0.39 (P < .0001). Conclusion: Using synovial thickness assessed on gadolinium-enhanced sequences as the reference, effusion-synovitis showed superior correlations and sensitivity. Effusion-synovitis should be preferred over Hoffa-synovitis as a surrogate marker for synovial thickening, in studies of knee OA for which gadolinium-enhanced sequences are not available.

  • 193.
    Crow, Mary K.
    et al.
    Weill Cornell Med Coll, Hosp Special Surg Weill, Mary Kirkland Ctr Lupus Res, New York, NY 10065 USA.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Type I interferons in host defence and inflammatory diseases2019Ingår i: Lupus Science and Medicine, ISSN 2053-8790, E-ISSN 1625-9823, Vol. 6, nr 1, artikel-id e000336Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Type I interferons (IFN) can have dual and opposing roles in immunity, with effects that are beneficial or detrimental to the individual depending on whether IFN pathway activation is transient or sustained. Determinants of IFN production and its functional consequences include the nature of the microbial or nucleic acid stimulus, the type of nucleic acid sensor involved in inducing IFN, the predominant subtype of type I IFN produced and the immune ecology of the tissue at the time of IFN expression. When dysregulated, the type I IFN system drives many autoimmune and non-autoimmune inflammatory diseases, including SLE and the tissue inflammation associated with chronic infection. The type I IFN system may also contribute to outcomes for patients affected by solid cancers or myocardial infarction. Significantly more research is needed to discern the mechanisms of induction and response to type I IFNs across these diseases, and patient endophenotyping may help determine whether the cytokine is acting as 'friend' or 'foe', within a particular patient, and at the time of treatment. This review summarises key concepts and discussions from the second International Summit on Interferons in Inflammatory Diseases, during which expert clinicians and scientists evaluated the evidence for the role of type I IFNs in autoimmune and other inflammatory diseases.

  • 194. Crowson, Cynthia S.
    et al.
    Rollefstad, Silvia
    Ikdahl, Eirik
    Kitas, George D.
    van Riel, Piet L. C. M.
    Gabriel, Sherine E.
    Matteson, Eric L.
    Kvien, Tore K.
    Douglas, Karen
    Sandoo, Aamer
    Arts, Elke
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Innala, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Karpouzas, George
    Dessein, Patrick H.
    Tsang, Linda
    El-Gabalawy, Hani
    Hitchon, Carol
    Pascual Ramos, Virginia
    Contreras Yanez, Irazu
    Sfikakis, Petros P.
    Zampeli, Evangelia
    Gonzalez-Gay, Miguel A.
    Corrales, Alfonso
    van de laar, Mart
    Vonkeman, Harald E.
    Meek, Inger
    Samb, Anne Grete
    Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, nr 1, s. 48-54Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA. Methods: In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions. Results: 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics). Conclusions: In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.

  • 195. Cvetkovic, Jasmina Trifunovic
    et al.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stegmayr, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lefvert, Ann Kari
    Susceptibility for and clinical manifestations of rheumatoid arthritis are associated with polymorphisms of the TNF-alpha, IL-1 beta, and IL-lRa genes2002Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 29, nr 2, s. 212-219Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To analyze the association of genetic polymorphisms of pro-inflammatory cytokines with rheumatoid arthritis (RA) in comparison with healthy controls from Northern Sweden and the potential contribution of these genetic variants for disease severity and development of cardiovascular complications.

    Methods. Polymerase chain reaction amplification was used for analysis of TaqI restriction fragment length polymorphism (RFLP) of interleukin-1 beta (IL-1beta), variable tandem repeat polymorphism of IL-1 receptor antagonist (IL-1Ra) gene and NcoI RFLP at position -308 of tumor necrosis factor-alpha (TNF-alpha) gene, One hundred and fifty-four patients with RA, 42 men and 112 women, were consecutively recruited into the study through the Department of Rheumatology.

    Results. The allele A1 of TNF-alpha was more common in the patient group (p < 0.01 OR = 1.62). Patients having the genotype A1A2 seemed to develop more severe disease compared with patients with A1A1 genotype: they were younger at disease onset (p < 0.05), had a higher accumulated disease activity (p < 0.05) and worse functional class (p < 0.05), Patients with genotype A2A2 of IL-1beta had higher accumulated disease activity score than patients with A1A1 and A1A2 (p < 0.05). The allelic combination A1 IL-1beta/A2 IL-1Ra was less prevalent in RA patients who developed cardiovascular complications (p < 0.005 OR = 0.20).

    Conclusions. The A1 allele of TNF-alpha associates with RA. Genotypes A1A2 of TNF-alpha and A2A2 of IL-1beta are associated with more severe disease. The allelic combination A1 IL-1beta/A2 IL-1Ra is less often present in RA patients who developed cardiovascular complications.

  • 196.
    Dahlqvist, Solbritt Rantapää
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Genetic-markers in rheumatoid-arthritis1986Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 15, nr Suppl. 58, s. 1-29Artikel i tidskrift (Refereegranskat)
  • 197.
    Dahlqvist, Solbritt Rantapää
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Beckman, G
    Beckman, L
    Serum-protein markers in systemic lupus-erythematosus1988Ingår i: Human Heredity, ISSN 0001-5652, E-ISSN 1423-0062, Vol. 38, nr 1, s. 44-47Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Serum protein markers (α1-AT, Bf, C3, C4A, C4B, Hp and Tf) were studied in a series of 36 patients with systemic lupus erythematosus (SLE) and compared to normal blood donors. In agreement with the results of previous investigations a significant increase of complement C4 deficiency was found among the SLE patients. The relative risks for AQO and BQ0 homozygosity were 7.2 and 4.1, respectively. Simultaneous occurrence of AQO and BQ0 was found in three patients with a calculated relative risk of about 65. A significant increase of the haptoglobin type 2–2 (p < 0.05) was found among SLE patients. The remaining serum protein systems showed no statistically significant associations with SLE.

  • 198.
    Dahlqvist, Solbritt Rantapää
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Beckman, L
    Transferrin c subtypes and rheumatoid-arthritis1985Ingår i: Human Heredity, ISSN 0001-5652, E-ISSN 1423-0062, Vol. 35, nr 5, s. 279-282Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transferrin C subtypes were studied in patients with rheumatoid arthritis (RA) and controls. A significant association was found between the C2 type and RA. This association concerned mainly male patients and patients with a family history of polyarthritis. The results were discussed in relation to previous studies of the role of oxygen free radicals in the pathogenesis of RA and to a recently proposed hypothesis that the TfC2 gene confers an increased risk for cellular damage by hydroxyl radicals.

  • 199.
    Dahlqvist, Solbritt Rantapää
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Beckman, Lars
    Serum-protein markers in ankylosing-spondylitis1987Ingår i: Human Heredity, ISSN 0001-5652, E-ISSN 1423-0062, Vol. 37, nr 6, s. 354-358Artikel i tidskrift (Refereegranskat)
  • 200.
    Dahlqvist, Solbritt Rantapää
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Landberg, G
    Department of Pathology, University Hospital S-901 85 Umeå, Sweden.
    Roos, G
    Department of Pathology, University Hospital S-901 85 Umeå, Sweden.
    Norberg, B
    Department of Internal Medicine, University Hospital S-901 85 Umeå, Sweden.
    Cell-cycle effects of the antirheumatic agent cph821994Ingår i: British Journal of Rheumatology, ISSN 0263-7103, E-ISSN 1460-2172, Vol. 33, nr 4, s. 327-331Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The benzylidated podophyllotoxin glycoside CPH82, a potentially useful drug for treatment of RA, was tested in vitro on nine human haematopoietic cell lines for cell kinetic effects. Previous studies have shown CPH82 to behave like a colchinetype ‘metaphase’ blocker.The distribution of cells within different cell cycle compartments (G1, S, G2 and M) was analysed by a novel method using dual parameter flow cytometric analysis of stage specific antigens (proliferating cell nuclear antigen and Ki-67). With CPH82 concentrations chosen to mimic clinical conditions, eight out of nine lines showed an accumulation of cells in the G2 phase of the cell cycle. In many lines a delayed progress through S seemed to occur. Three lines were blocked in both G1 and G2, whereas the major effect on one line (HL-60) was an accumulation of cells in the G1 phase. Progression of M cells seemed only slightly delayed for some cell lines. In comparison with two related ‘metaphase’ blocking agents (podophyllotoxin and taxol), CPH82 had a different and dose-dependent pattern of cell cycle retardation. It is speculated that the cell kinetic action of CPH82 might give insight into the question why it, unlike other ‘metaphase’ blockers, has proved valuable in the treatment of RA.

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