Ändra sökning
Avgränsa sökresultatet
1234 1 - 50 av 187
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Ahlström, Håkan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Feltelius, N
    Nyman, Rickard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Hällgren, Roger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Magnetic resonance imaging of sacroiliac joint inflammation1990Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 33, nr 12, s. 1763-1769Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A consecutive series of 27 patients with symptoms compatible with sacroiliitis underwent magnetic resonance imaging (MRI) of the sacroiliac joints. The diagnostic sensitivity of MRI was similar to that of computed tomography or conventional radiography. However, MRI seems to have the potential of providing unique information about the disease process in sacroiliitis by demonstrating abnormalities in subchondral bone and periarticular bone marrow. The results of this study suggest that early inflammatory changes in sacroiliitis occur in the subchondral structures of the sacroiliac joints.

  • 2. Ahmed, Aisha S.
    et al.
    Li, Jian
    Ahmed, Mahmood
    Hua, Long
    Yakovleva, Tatiana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Ossipov, Michael H.
    Bakalkin, Georgy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Stark, André
    Attenuation of Pain and Inflammation in Adjuvant-Induced Arthritis by the Proteasome Inhibitor MG1322010Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 62, nr 7, s. 2160-2169Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. In rheumatoid arthritis (RA), pain and joint destruction are initiated and propagated by the production of proinflammatory mediators. Synthesis of these mediators is regulated by the transcription factor NF-kappa B, which is controlled by the ubiquitin proteasome system (UPS). The present study explored the effects of the proteasome inhibitor MG132 on inflammation, pain, joint destruction, and expression of sensory neuropeptides as markers of neuronal response in a rat model of arthritis. Methods. Arthritis was induced in rats by injection of heat-killed Mycobacterium butyricum. Arthritis severity was scored, and nociception was evaluated by mechanical pressure applied to the hind paw. Joint destruction was assessed by radiologic and histologic analyses. NF-kappa B DNA-binding activity was analyzed by electromobility shift assay, and changes in the expression of the p50 NF-kappa B subunit and the proinflammatory neuropeptides substance P (SP) and calcitonin generelated peptide (CGRP) were detected by immunohistochemistry. Results. Arthritic rats treated with MG132 demonstrated a marked reduction in inflammation, pain, and joint destruction. The elevated DNA-binding activity of the NF-kappa B/p50 homodimer and p50, as well as the neuronal expression of SP and CGRP, observed in the ankle joints of arthritic rats were normalized after treatment with MG132. Conclusion. In arthritic rats, inhibition of proteasome reduced the severity of arthritis and reversed the pain behavior associated with joint inflammation. These effects may be mediated through the inhibition of NF-kappa B activation and may possibly involve the peripheral nervous system. New generations of nontoxic proteasome inhibitors may represent a novel pharmacotherapy for RA.

  • 3. Akkoc, Nurullah
    et al.
    Sari, Ismail
    Akar, Servet
    Binicier, Omer
    Thomas, Mark G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik.
    Weale, Michael E.
    Birlik, Merih
    Savran, Yusuf
    Onen, Fatos
    Bradman, Neil
    Plaster, Christopher A.
    Increased Prevalence of M694V in Patients With Ankylosing Spondylitis: Additional Evidence for a Link With Familial Mediterranean Fever2010Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 62, nr 10, s. 3059-3063Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To assess whether there is a statistically significant difference in the frequency of common MEFV allele variants in patients with ankylosing spondylitis (AS) as compared with control patients with rheumatoid arthritis (RA) and with healthy control subjects. Methods. Sixty-two patients with AS, 50 healthy control subjects, and 46 patients with RA were assessed for the presence of MEFV variants. Exon 10 was analyzed by direct sequencing. E148Q was analyzed by restriction endonuclease enzyme digestion (REED) or by direct sequencing when REED analysis failed. Results. The allele frequency of all MEFV variants in the AS group was significantly higher than that in the pooled control group of healthy subjects plus RA patients (15.3% versus 6.8%; P = 0.021). M694V was the only variant that was significantly more common in the AS group than in the combined or individual control groups (P = 0.026 for AS patients versus healthy controls, P = 0.046 for AS patients versus RA patient controls, and P = 0.008 for AS patients versus healthy and RA patient control groups). The carriage rate of M694V was also significantly higher in the AS patient group than in the combined control group (odds ratio 7.0, P = 0.014). Neither M694V nor any other MEFV variant showed a correlation with most of the disease-related measures examined. Conclusion. We found an increased frequency of MEFV variants in AS patients as compared with healthy controls and with RA patient controls. This was primarily due to the presence of M694V. The roles of other exon 10 variants, as well as the relationship between the variant status and the severity and clinical course of the disease, need to be explored in further studies that include sufficiently large sample sizes.

  • 4. Alenius, Gerd-Marie
    et al.
    Husmark, Tomas
    Theander, Elke
    Larsson, Per
    Geijer, Mats
    Teleman, Annika
    Lindqvist, Ulla R. C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rheumatoid Arthritis, a More Severe Disease Than Psoriatic Arthritis?: A Comparison Of Disease Activity In Patients With Psoriatic Arthritis and Rheumatoid Arthritis From The Swedish Early Psoriatic Arthritis Registry (SwePsA) and The Swedish Rheumatology Registry For Early Rheumatoid Arthritis (SRR)2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Suppl. 10, s. S150-S150Artikel i tidskrift (Övrigt vetenskapligt)
  • 5.
    Alenius, Gerd-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Husmark, Tomas
    Theander, Elke
    Larsson, Per
    Geijer, Mats
    Teleman, Annika
    Lindqvist, Ulla R. C.
    Rheumatoid Arthritis, a More Severe Disease Than Psoriatic Arthritis?: A Comparison Of Disease Activity In Patients With Psoriatic Arthritis and Rheumatoid Arthritis From The Swedish Early Psoriatic Arthritis Registry (SwePsA) and The Swedish Rheumatology Registry For Early Rheumatoid Arthritis (SRR)2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Special issue, Supplement 10, s. S150-S150, Meeting Abstract: 346Artikel i tidskrift (Övrigt vetenskapligt)
  • 6. Andersen, Grethe N.
    et al.
    Nagaeva, Olga
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Wikberg, Jarl E. S.
    The Melanocortin System: A New and Important Actor on the Scene of Systemic Sclerosis2011Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 63, nr 10, s. S908-S908Artikel i tidskrift (Refereegranskat)
  • 7.
    Andersen, Grethe Neumann
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Caidahl, Kenneth
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Kazzam, Elsadig
    Petersson, Ann-Sofi
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis: findings with the soluble adhesion molecules E-selectin, intercellular adhesion molecule 1, and vascular adhesion molecule 12000Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 43, nr 5, s. 1085-1093Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate whether production of endothelial-derived nitric oxide (NO) is disturbed in this disease.

    Methods We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how these variables were related to one another. Plasma nitrate and 24-hour-urinary excretion of nitrate in patients and controls were measured after a 72-hour nitrate-free-diet, using a gas chromatography/mass spectrometric method. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin and cytokines were measured by enzyme-linked immunosorbent assay. The expression of E-selectin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting.

    Results Plasma nitrate and 24-hour-urinary-excretion of cGMP were significantly elevated in patients compared with controls, while 24-hour-urinary-excretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in the patients. Levels of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a significant correlation with sICAM-1 (P = 0.055), suggesting that activated endothelial cells may produce plasma nitrate.

    Conclusion NO synthesis is elevated in SSc patients, and the activated endothelial cell is a likely site of its production.

  • 8.
    Andersen, Grethe Neumann
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Kazzam, Elsadig
    Mälar Hospital, Eskilstuna, Sweden.
    Nyberg, Gunnar
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Klintland, Natalia
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Petersson, Ann-Sofi
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Caidahl, Kenneth
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Assessment of vascular function in systemic sclerosis: indications of the development of nitrate tolerance as a result of enhanced endothelial nitric oxide production2002Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 46, nr 5, s. 1324-1332Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate the relationship between endothelium-dependent and endothelium-independent functions and the stiffness of conduit arteries as well as levels of endothelial activation markers in patients with systemic sclerosis (SSc).

    METHODS: Endothelium-dependent (i.e., flow-mediated) and endothelium-independent (i.e., nitroglycerin-induced) dilation of the brachial artery was measured as the percentage of change from baseline (FMD% and NTG%, respectively) in 24 SSc patients and 24 age- and sex-matched healthy controls by high-resolution ultrasound imaging. The maximum increase in systolic pressure per unit of time (dP/dt(max)), as a measure of arterial wall stiffness, was assessed in the radial artery by pulse applanation tonometry. Plasma nitrate, the most important metabolite of nitric oxide, and 24-hour urinary excretion of nitrate were measured by gas chromatography mass spectrometry. Soluble E-selectin and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay.

    RESULTS: Brachial artery FMD% and NTG% did not differ between SSc patients and controls. Radial artery dP/dt(max) was significantly increased in the patients and correlated significantly with elevated levels of plasma nitrate and sVCAM-1. Twenty-four-hour urinary nitrate excretion tended to be elevated. Brachial artery NTG% was significantly inversely correlated with levels of plasma nitrate and soluble endothelial adhesion molecules.

    CONCLUSION: The ability of the brachial arteries to dilate in response to hyperemia and nitroglycerin challenge is preserved in SSc. Stiffness of the radial artery is increased, however. Endothelial activation seems to determine the extent of the brachial artery NTG% and the radial artery dP/dt(max). The data are compatible with the hypothesis that nitrate tolerance is present in the vascular smooth muscle cells of the brachial artery wall in SSc.

  • 9. Apel, Maria
    et al.
    Uebe, Steffen
    Bowes, John
    Giardina, Emiliano
    Korendowych, Eleanor
    Juneblad, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Pasutto, Francesca
    Ekici, Arif B.
    McManus, Ross
    Ho, Pauline
    Bruce, Ian N.
    Ryan, Anthony W.
    Behrens, Frank
    Boehm, Beate
    Traupe, Heiko
    Lohmann, Joerg
    Gieger, Christian
    Wichmann, Heinz-Erich
    Padyukov, Leonid
    FitzGerald, Oliver
    Alenius, Gerd-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    McHugh, Neil J.
    Novelli, Giuseppe
    Burkhardt, Harald
    Barton, Anne
    Reis, Andre
    Hueffmeier, Ulrike
    Variants in RUNX3 Contribute to Susceptibility to Psoriatic Arthritis, Exhibiting Further Common Ground With Ankylosing Spondylitis2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr 5, s. 1224-1231Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective Psoriatic arthritis (PsA) is a common inflammatory joint disease distinct from other chronic arthritides and frequently accompanied by psoriasis vulgaris. In a first genome-wide association study (GWAS), we were able to identify several genetic risk factors. However, even combined with previously identified factors, the genetic contribution to disease was not fully explained. Therefore, we undertook this study to investigate further 17 loci from our GWAS that did not reach genome-wide significance levels of association in the initial analysis. Methods Twenty-one of 22 single-nucleotide polymorphisms were successfully genotyped in independent cohorts of 1,398 PsA patients and 6,389 controls and in a group of 964 German patients with psoriasis vulgaris. Results Association with a RUNX3 variant, rs4649038, was replicated in independent patients and controls and resulted in a combined P value of 1.40 x 108 by Cochran-Mantel-Haenszel test and an odds ratio (OR) of 1.24 (95% confidence interval [95% CI] 1.151.33). Further analyses based on linkage disequilibrium (LD) at RUNX3 refined the most significant association to an LD block located in the first intron of one isoform. Weaker evidence for association was detected in German patients with psoriasis vulgaris (P = 5.89 x 102; OR 1.13 [95% CI 1.001.28]), indicating a role in the skin manifestations of psoriasis. Conclusion Our analyses identified variants in RUNX3 as susceptibility factors for PsA. RUNX3 has already been implicated in susceptibility to ankylosing spondylitis, another spondyloarthritis, although its risk allele is independent from the one for PsA. RUNX-3 is involved in CD8+ T lymphocyte differentiation and is therefore a good candidate for involvement in PsA and psoriasis vulgaris as T cellmediated diseases.

  • 10. Arkema, Elizabeth V.
    et al.
    Jonsson, Jerker
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rutting, Maud
    Bruchfeld, Judith
    Feltelius, Nils
    Askling, Johan
    Are Patients With Rheumatoid Arthritis Still At An Increased Risk Of Tuberculosis and What Is The Role Of Biological Treatment?2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Suppl. 10, s. S719-S719Artikel i tidskrift (Övrigt vetenskapligt)
  • 11. Arlestig, L
    et al.
    Wiklund, P G
    Dahlqvist, Solbritt Rantapää
    Polymorphism of genes affecting atherothrombotic disease evaluated in rheumatoid arthritis.2003Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 48Artikel i tidskrift (Refereegranskat)
  • 12. Arlestig, Lisbeth
    et al.
    Brink, Mikael
    Hansson, Monika
    Jakobsson, Per Johan
    Holmdahl, Rikard
    Mathsson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Klareskog, Lars
    Rantapaa-Dahlqvist, Solbritt M.
    Single Nucleotide Polymorphisms within the HLA-DRB1 Gene in Relation to Antibodies Against Citrullinated Peptides in Individuals Prior to the Development of Rheumatoid Arthritis2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr S10, s. S180-S180Artikel i tidskrift (Övrigt vetenskapligt)
  • 13. Askling, Johan
    et al.
    Fored, C. Michael
    Brandt, Lena
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Bertilsson, Lennart
    Cöster, Lars
    Geborek, Pierre
    Jacobsson, Lennart T.
    Lindblad, Staffan
    Lysholm, Jörgen
    Rantapää-Dahlqvist, Solbritt
    Saxne, Tore
    Romanus, Victoria
    Klareskog, Lars
    Feltelius, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden2005Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 52, nr 7, s. 1986-1992Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA.

    METHODS:

    Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004.

    RESULTS:

    During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment.

    CONCLUSION:

    Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.

  • 14. Askling, Johan
    et al.
    Fored, M.
    Brandt, L.
    Baecklund, E.
    Bertilsson, L.
    Coster, L.
    Geborek, P.
    Jacobsson, L.
    Lindblad, S.
    Lysholm, J.
    Rantapää-Dahlqvist, Solbritt
    Saxne, T.
    van Vollenhoven, R.
    Feltelius, N.
    Klareskog, L.
    TNF-antagonist treatment and risk of hospitalisation for cardiovascular disease. Results from the National Swedish Monitoring-Program for Biologies in Ra (ARTIS).2006Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 54Artikel i tidskrift (Refereegranskat)
  • 15. Askling, Johan
    et al.
    Fored, M.
    Brandt, L.
    Baecklund, E.
    Bertilsson, L.
    Coster, L.
    Geborek, P.
    Jacobsson, L.
    Lindblad, S.
    Lysholm, J.
    Rantapää-Dahlqvist, Solbritt
    Saxne, T.
    van Vollenhoven, R.
    Feltelius, N.
    Klareskog, L.
    TNF-antagonist treatment and risk of hospitalisation for infection. Results from the National Swedish Monitoring-Program for Biologics in RA (ARTIS).2006Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 54Artikel i tidskrift (Refereegranskat)
  • 16. Askling, Johan
    et al.
    Fored, Michael
    Brandt, Lena
    Baecklund, Eva
    Bertilsson, Lennart
    Cöster, Lars
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Reumatologi. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Geborek, Pierre
    Jacobsson, Lennart T
    Lindblad, Staffan
    Lysholm, Jörgen
    Rantapää-Dahlqvist, Solbritt
    Saxne, Tore
    Romanus, Victoria
    Klareskog, Lars
    Feltelius, Nils
    Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden2005Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 52, nr 7, s. 1986-1992Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA. Methods. Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004. Results. During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment. Conclusion. Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept. © 2005, American College of Rheumatology.

  • 17.
    Askling, Johan
    et al.
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    van Vollenhoven, Ronald F
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Granath, Fredrik
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Raaschou, Pauline
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Fored, C Michael
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Baecklund, Eva
    Uppsala University Hospital, Uppsala, Sweden.
    Dackhammar, Christina
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Feltelius, Nils
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden, and Medical Products Agency, Uppsala, Sweden.
    Cöster, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Geborek, Pierre
    Lund University Hospital, Lund, Sweden.
    Jacobsson, Lennart T
    Malmö University Hospital, Malmö, Sweden.
    Lindblad, Staffan
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Rantapaa-Dahlqvist, Solbritt
    Norrland University Hospital, Umeå, Sweden.
    Saxne, Tore
    Lund University Hospital, Lund, Sweden.
    Klareskog, Lars
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Cancer Risk in Patients With Rheumatoid Arthritis Treated With Anti-Tumor Necrosis Factor alpha Therapies Does the Risk Change With the Time Since Start of Treatment?2009Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, nr 11, s. 3180-3189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To determine the short-term and medium-term risks of cancer in patients receiving antitumor necrosis factor alpha (anti-TNF alpha) therapies that have proven effective in the treatment of chronic inflammatory conditions. Methods. By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received. Results. During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed. Conclusion. During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.

  • 18. Askling, Johan
    et al.
    van Vollenhoven, Ronald F.
    Granath, Fredrik
    Raaschou, Pauline
    Fored, C. Michael
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Dackhammar, Christina
    Feltelius, Nils
    Cöster, Lars
    Geborek, Pierre
    Jacobsson, Lennart T.
    Lindblad, Staffan
    Rantapää-Dahlqvist, Solbritt
    Saxne, Tore
    Klareskog, Lars
    Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies: does the risk change with the time since start of treatment?2009Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, nr 11, s. 3180-3189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions.

    METHODS:

    By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received.

    RESULTS:

    During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed.

    CONCLUSION:

    During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.

  • 19.
    Askling, Johan
    et al.
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    van Vollenhoven, Ronald F
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Granath, Fredrik
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Raaschou, Pauline
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Fored, C Michael
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Baecklund, Eva
    Uppsala University Hospital, Uppsala, Sweden.
    Dackhammar, Christina
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Feltelius, Nils
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Cöster, Lars
    Linköping University Hospital, Linköping, Sweden.
    Geborek, Pierre
    Lund University Hospital, Lund, Sweden.
    Jacobsson, Lennart T
    Malmö University Hospital, Malmö, Sweden.
    Lindblad, Staffan
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Saxne, Tore
    Lund University Hospital, Lund, Sweden.
    Klareskog, Lars
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor α therapies: does the risk change with the time since start of treatment?2009Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, nr 11, s. 3180-3189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions. METHODS: By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received. RESULTS: During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed. CONCLUSION: During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.

  • 20. Augustsson, Jenny
    et al.
    Jacobsson, Lennart T. H.
    Nilsson, Jan-Ake
    Teleman, Annika
    Petersson, Ingemar F.
    Rantapää-Dahlqvist, Solbritt
    van Vollenhoven, Ronald F.
    Very early improvement in hand function predicts favourable response in RA patients treated with adalimumab2008Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 58Artikel i tidskrift (Refereegranskat)
  • 21. Augustsson, Jenny
    et al.
    van Vollenhoven, Ronald F.
    Nilsson, Jan-Ake
    Teleman, Annika
    Petersson, Ingemar
    Rantapää-Dahlqvist, Solbritt
    Jacobsson, Lennart T. H.
    Patient-reported swollen and tender 28-joint counts accurately represent RA disease activity and can be used to calculate DAS28 on a group level2008Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 58Artikel i tidskrift (Refereegranskat)
  • 22.
    Baecklund, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Iliadou, Anastasia
    Granath, Fredrik
    Ekbom, Anders
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Feltelius, Nils
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Klareskog, Lars
    Askling, Johan
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis2006Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 54, nr 12, s. 3774-3781Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, with a correlation between RA disease severity and lymphoma risk, most pronounced for diffuse large B cell lymphomas (DLBCLs), which also constitute the majority of RA-associated lymphomas. DLBCLs can be further subdivided into germinal center (GC)-like and non-GC-like subtypes, with different cellular origins and prognoses. This study was undertaken to investigate whether RA displays a specific association with any of the DLBCL subtypes.

    METHODS:

    We identified 139 patients with DLBCLs within a population-based case-control study of 378 RA patients with lymphoma. The DLBCLs were examined for CD10, Bcl-6, and interferon regulatory factor 4 expression patterns, subclassified into GC and non-GC subtypes, and then correlated with clinical parameters.

    RESULTS:

    We found a statistically significant predominance of the non-GC subtype (97 patients; 70% of all DLBCLs). These patients more often had an advanced stage of lymphoma at diagnosis and had a worse 5-year overall survival rate (16% versus 33%) compared with patients with the GC subtype. There was a strong association with RA disease activity in both subtypes, with >70% of the GC and non-GC cases occurring in RA patients with the highest overall disease activity scores.

    CONCLUSION: These findings suggest that severe RA is particularly associated with the non-GC subtype of DLBCL, and indicate a critical role of activated peripheral B cells as the cells of origin in these lymphomas.

  • 23.
    Baecklund, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Iliadou, Anastasia
    Askling, Johan
    Ekbom, Anders
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Granath, Fredrik
    Catrina, Anca Irinel
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Feltelius, Nils
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Klareskog, Lars
    Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis2006Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 54, nr 3, s. 692-701Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective.

    METHODS:

    We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments.

    RESULTS:

    The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas.

    CONCLUSION:

    Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant.

  • 24. Balboni, Imelda
    et al.
    Niewold, Timothy B
    Morgan, Gabrielle
    Limb, Cindy
    Eloranta, Maija-Leena
    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.
    Utz, Paul J
    Pachman, Lauren M
    Brief Report: Interferon-α Induction and Detection of Anti-Ro, Anti-La, Anti-Sm, and Anti-RNP Autoantibodies by Autoantigen Microarray Analysis in Juvenile Dermatomyositis2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr 9, s. 2424-2429Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective:

    To evaluate serum interferon- (IFN) activity in the context of autoantibody profiles in patients with juvenile dermatomyositis (JDM). 

    Methods:

    Sera from 36 patients with JDM were analyzed. Autoantibody profiles were determined by probing microarrays, which were fabricated with approximate to 80 distinct autoantigens, with serum and a Cy3-conjugated secondary antibody. Arrays were scanned and analyzed to determine antigen reactivity. Serum IFN activity was measured using a functional reporter cell assay. Sera were assayed alone or in combination with cellular material released from necrotic U937 cells to stimulate peripheral blood mononuclear cells from healthy donors in vitro, and IFN production in culture was measured by a dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). 

    Results:

    Reactivity against at least 1 of 41 autoantigens on the microarray, including Ro 52, Ro 60, La, Sm, and RNP, was observed in 75% of the serum samples from patients with JDM. IFN activity was detected in 7 samples by reporter cell assay. The reporter cell assay showed a significant association of reactivity against Ro, La, Sm, and proliferating cell nuclear antigen with serum IFN activity (P = 0.005). Significance Analysis of Microarrays (SAM) identified increased reactivity against Sm, RNP, Ro 52, U1-C, and Mi-2 in these sera. Sixteen samples induced IFN production as measured by DELFIA, and there was a significant association of reactivity against Ro, La, Sm, and RNP with the induction of IFN by serum and necrotic cell material (P = 0.034). SAM identified increased reactivity against Ro 60 in these sera. 

    Conclusion:

    These data support the hypothesis that nucleic acid-associated autoantibodies, including the Ro/La and Sm/RNP complexes, may stimulate the production of active IFN in children with JDM.

  • 25. Bengtsson, Anders A
    et al.
    Sturfelt, Gunnar
    Lood, Christian
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    van Vollenhoven, Ronald F
    Axelsson, Bengt
    Sparre, Birgitta
    Tuvesson, Helén
    Wallén Öhman, Marie
    Leanderson, Tomas
    Pharmacokinetics, tolerability, and preliminary efficacy of ABR-215757, a new quinoline-3-carboxamide derivative, in murine and human SLE2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr 5, s. 1579-1588Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To assess the efficacy of ABR-215757, a new immunomodulatory small molecule in a murine SLE model, to evaluate the pharmacokinetics and tolerability in SLE patients at doses predicted to be efficacious and safe, and to determine the maximum tolerated dose (MTD).

    METHODS: The efficacy of ABR-215757 was studied in lupus prone MRLlpr/lpr mice and compared with established SLE treatments. Dose response data of ABR-215757 were together with pharmacokinetic data used to calculate effective and safe clinical doses. The pharmacokinetics and tolerance of ABR-215757 were evaluated in a Phase Ib double-blind, placebo controlled, dose-escalation study where cohorts of SLE patients received daily oral treatment for 12 weeks.

    RESULTS: Disease inhibition in MRLlpr/lpr mice, comparable to that of prednisolone and mycophenolate mofetil, was obtained with ABR-215757. Prominent effects on disease manifestations, serological markers and a steroid sparing effect were seen for ABR-215757. The pharmacokinetic properties in SLE patients were linear and well suitable for once daily oral treatment. The majority of the adverse events (AEs) were mild or moderate and transient. The most frequent AEs were arthralgia and myalgia, reported at the highest (4.5 and 6 mg/day) dose levels. At 4.5 mg and higher some AEs of severe intensity and serious adverse events (SAEs) were reported.

    CONCLUSION: ABR-215757 effectively inhibited disease and had a steroid sparing effect in experimental lupus. Clinical doses up to 3 mg/day, dose levels predicted from pre-clinical studies to be efficacious and safe, were well tolerated in the SLE patients. The MTD was concluded to be 4.5 mg/day.

  • 26.
    Berggren, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Alexsson, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Alm, Gunnar V.
    Syvanen, Ann-Christine
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Variation of Interferon-Alpha Production in Healthy Individuals and Association with Autoimmune Susceptibility Genes2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr S10, s. S961-S961Artikel i tidskrift (Övrigt vetenskapligt)
  • 27.
    Berggren, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hagberg, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Weber, Gert
    Alm, Gunnar V
    Rönnblom, Lars
    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.
    B lymphocytes enhance the interferon-α production by plasmacytoid dendritic cells2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr 10, s. 3409-3419Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    Type I interferon (IFN) system and B cells are activated in many autoimmune diseases, e.g. systemic lupus erythematosus (SLE). IFNα produced by plasmacytoid dendritic cells (pDC) stimulate several B cell functions, including autoantibody production. However, not much is known how B cells influence the pDC function. We therefore investigated the regulatory effect of B cells on IFNα production by pDC.

    METHODS:

    PDC and B cells from healthy blood donor PBMC were stimulated with RNA-containing immune complexes (RNA-IC) consisting of U1 snRNP and IgG from SLE patients, herpes simplex virus (HSV) or oligonucleotide ODN2216, alone or in co-cultures. IFNα, several other cytokines and pDC or B cell-associated surface molecules were analyzed by immunoassays or flow cytometry.

    RESULTS:

    B cells enhanced the IFNα production by pDC up to 47-fold, and the effect was most pronounced for pDC stimulated with RNA-IC. Anti-CD31 antibody reduced the RNA-IC-induced IFNα production by 80%, but not when ODN2216 was used as IFN-inducer. Supernatants from ODN2216-stimulated B cells promoted IFNα production by pDC, while supernatants from RNA-IC-stimulated B cells did not.

    CONCLUSION:

    Our results reveal a novel B cell function, enhancing the type I IFN production by pDC. Since B cells are activated by type I IFN, this pDC-B cell cross-talk might be of fundamental importance in the etiopathogenesis of SLE, and contribute to a chronic immune activation in SLE and other systemic rheumatic diseases.

  • 28. Berglin, E
    et al.
    Padyukov, L
    Hallmans, G
    van Venrooji, W J
    Klareskog, L
    Dahlqvist, Solbritt Rantapää
    Antibodies against cyclic citrullinated peptide (CCP) and shared epitope predict rheumatoid arthritis.2003Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 48Artikel i tidskrift (Refereegranskat)
  • 29. Berglin, E
    et al.
    Sundin, U
    Jidell, E
    Wadell, G
    Hallman, G
    Dahlqvist, Solbritt Rantapää
    Antibodies against cyclic citrullinated peptide before disease onset predict radiological outcome of rheumatoid arthritis2004Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 50Artikel i tidskrift (Refereegranskat)
  • 30.
    Berglin, Ewa H.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Does Evaluation Of Hand Bone Loss By Digital x-Ray Radiogrammetry Within The First 3 Months After Diagnosis Of Rheumatoid Arthrits Identify Patients At Risk For Radiological Progression?2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Special issue, Supplement 10, s. S834-S834, Meeting Abstract: 1958Artikel i tidskrift (Övrigt vetenskapligt)
  • 31.
    Berglin, Ewa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Comparison of the 1987 ACR and 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis in Clinical Practice2011Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 63, nr 10, s. S117-S117Artikel i tidskrift (Refereegranskat)
  • 32.
    Bergman, Stefan
    et al.
    Spenshult Research and Development Center, Halmstad, Sweden.
    Bremander, Ann
    Spenshult Research and Development Center, Halmstad, Sweden.
    Lifestyle factors were seldom discussed with patients visiting a rheumatology clinic2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Special issue, Supplement 10, s. S982-S983, Meeting Abstract: 2307Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Purpose: There is increasing evidence that lifestyle factors are of importance for outcome of rheumatic diseases, and lifestyle interventions should be a natural part of management.

    The aim was to study if lifestyle factors (diet, physical activity, smoking and alcohol use) were discussed with patients on a regular visit to a specialized rheumatology clinic.

    Methods: A questionnaire was distributed to 318 patients visiting an outpatient clinic, and 223 (70%) responded. The questionnaire assessed if lifestyle factors (diet, physical activity, smoking and alcohol use) were discussed at the visit. If not, it also assessed if the patients themselves felt that this discussion would have been desirable.

    Results: The questionnaire was answered by 69 (31%) men and 154 (69%) women, and 69% were younger than 65 years. Diet was more frequently discussed with men (14.7% vs. 4.8%) although more women (11.6% vs 4.4%) would have desired it to be discussed. 83% of the patients did not consider that it was needed to discuss at all. Physical activity was discussed with 28% of the patients, without any significant difference between men and women. Only 8% of those not having this discussion thought that they needed it. Smoking was discussed with 15%, without any significant difference between men and women. Alcohol use was discussed with more men than women (15.9% vs. 4.0%). Of those not having this discussion 3% of the women but none of the men thought that they needed it.

    Conclusion: Although recommended as part of management, lifestyle factors are seldom discussed with the patients, and this discussion is not actively thought for by the patients. Lifestyle factors are more frequently discussed with men although women would have desired to have this discussion to a higher extent. There is a need for health care to actively take the initiative and discuss lifestyle as part of regular care.

  • 33.
    Blomberg, Stina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eloranta, Maija-Leena
    Magnusson, Mattias
    Alm, Gunnar V.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Expression of the markers BDCA-2 and BDCA-4 and production of interferon-alpha by plasmacytoid dendritic cells in systemic lupus erythematosus2003Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 48, nr 9, s. 2524-32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To study the expression of blood dendritic cell antigen 2 (BDCA-2) and BDCA-4 molecules by plasmacytoid dendritic cells (PDCs) in the blood of patients with systemic lupus erythematosus (SLE), and to study PDC production of interferon-alpha (IFN alpha) and its inhibition by anti-BDCA-2 and anti-BDCA-4 antibodies. METHODS: Peripheral blood mononuclear cells (PBMCs) from SLE patients (SLE PBMCs) and from healthy controls were induced to produce IFN alpha in vitro by SLE serum containing an endogenous IFN alpha-inducing factor (SLE-IIF) or by herpes simplex virus type 1 (HSV-1). The frequencies and numbers of BDCA-2-, BDCA-3-, and BDCA-4-expressing cells were analyzed by flow cytometry, and the effects of anti-BDCA-2 and anti-BDCA-4 monoclonal antibodies (mAb) on IFN alpha production were investigated. RESULTS: IFN alpha production by SLE PBMCs induced by SLE-IIF or HSV-1 was decreased compared with that of healthy control PBMCs (P = 0.002 and P = 0.0007, respectively). The proportions of BDCA-2- and BDCA-3-expressing cells in SLE PBMCs were reduced compared with those in PBMCs from healthy controls (P = 0.01 and P = 0.004, respectively). IFN alpha producers in culture, especially among SLE PBMCs, displayed reduced BDCA-2 expression and constituted only a minority of the BDCA-2-positive cells, at least in healthy control PBMCs (median 18%). IFN alpha production by both SLE and healthy control PBMCs stimulated by SLE-IIF or HSV-1 was markedly reduced by anti-BDCA-2 mAb (median 81-98% inhibition). Anti-BDCA-4 mAb only partially inhibited SLE-IIF-induced IFN alpha production. CONCLUSION: SLE patients had a reduced number of BDCA-2-expressing PDCs, also termed natural IFN alpha-producing cells, and their IFN alpha production could be inhibited by anti-BDCA-2/4 mAb. Such mAb may be a therapeutic option for inhibiting the ongoing IFN alpha production in SLE patients.

  • 34.
    Blomberg, Stina
    et al.
    Uppsala University Hospital, Swedenj.
    Eloranta, Maija-Leena
    Swedish University of Agriculture Science, Uppsala, Sweden ).
    Magnusson, Mattias
    Swedish University of Agriculture Science, Uppsala, Sweden ).
    Alm, Gunnar V.
    Swedish University of Agriculture Science, Uppsala, Sweden ).
    Rönnblom, Lars
    Uppsala University Hospital, Sweden.
    Expression of the markers BDCA-2 and BDCA-4 and production of interferon-alpha by plasmacytoid dendritic cells in systemic lupus erythematosus2003Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 48, nr 9, s. 2524-2532Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    To study the expression of blood dendritic cell antigen 2 (BDCA-2) and BDCA-4 molecules by plasmacytoid dendritic cells (PDCs) in the blood of patients with systemic lupus erythematosus (SLE), and to study PDC production of interferon-α (IFNα) and its inhibition by anti–BDCA-2 and anti–BDCA-4 antibodies.

    Methods

    Peripheral blood mononuclear cells (PBMCs) from SLE patients (SLE PBMCs) and from healthy controls were induced to produce IFNα in vitro by SLE serum containing an endogenous IFNα-inducing factor (SLE-IIF) or by herpes simplex virus type 1 (HSV-1). The frequencies and numbers of BDCA-2–, BDCA-3–, and BDCA-4–expressing cells were analyzed by flow cytometry, and the effects of anti–BDCA-2 and anti–BDCA-4 monoclonal antibodies (mAb) on IFNα production were investigated.

    Results

    IFNα production by SLE PBMCs induced by SLE-IIF or HSV-1 was decreased compared with that of healthy control PBMCs (P = 0.002 and P = 0.0007, respectively). The proportions of BDCA-2– and BDCA-3–expressing cells in SLE PBMCs were reduced compared with those in PBMCs from healthy controls (P = 0.01 and P = 0.004, respectively). IFNα producers in culture, especially among SLE PBMCs, displayed reduced BDCA-2 expression and constituted only a minority of the BDCA-2–positive cells, at least in healthy control PBMCs (median 18%). IFNα production by both SLE and healthy control PBMCs stimulated by SLE-IIF or HSV-1 was markedly reduced by anti–BDCA-2 mAb (median 81–98% inhibition). Anti–BDCA-4 mAb only partially inhibited SLE-IIF–induced IFNα production.

    Conclusion

    SLE patients had a reduced number of BDCA-2–expressing PDCs, also termed natural IFNα-producing cells, and their IFNα production could be inhibited by anti–BDCA-2/4 mAb. Such mAb may be a therapeutic option for inhibiting the ongoing IFNα production in SLE patients.

  • 35.
    Brechter, Anna
    et al.
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Lerner, Ulf
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Bradykinin potentiates cytokine-induced prostaglandin biosynthesis in osteoblasts by enhanced expression of cyclooxygenase 2, resulting in increased RANKL expression2007Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 56, nr 3, s. 910-923Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Bradykinin (BK) stimulates bone resorption in vitro and synergistically potentiates interleukin-1 (IL-1)-induced bone resorption and prostaglandin (PG) formation, suggesting that kinins are important in inflammation-induced bone loss. The present study was undertaken to study 1) the role of the kinin B1 and B2 receptors in the synergistic interaction with IL-1 and tumor necrosis factor alpha (TNFalpha), 2) the molecular mechanisms involved in synergistic enhancement of PG formation, and 3) the effects of kinins on cytokine-induced expression of RANKL, RANK, and osteoprotegerin (OPG) (the latter being crucial molecules in osteoclast differentiation). METHODS: Formation of PGs, expression of enzymes involved in arachidonic acid metabolism, and expression of RANKL, RANK, and OPG were assessed in the human osteoblastic cell line MG-63 and in mouse calvarial bones. The role of NF-kappaB and MAP kinases was studied using pharmacologic inhibitors. RESULTS: PGE(2) formation and cyclooxygenase 2 (COX-2) protein expression were induced by IL-1beta and potentiated by kinins with affinity for the B1 or B2 receptors, resulting in PGE(2)-dependent enhancement of RANKL. The enhancements of PGE(2) formation and COX-2 were markedly decreased by inhibition of p38 and JNK MAP kinases, whereas inhibition of NF-kappaB resulted in abolishment of the PGE(2) response with only slight inhibition of COX-2. CONCLUSION: Kinin B1 and B2 receptors synergistically potentiate IL-1- and TNFalpha-induced PG biosynthesis in osteoblasts by a mechanism involving increased levels of COX-2, resulting in increased RANKL. The synergistic stimulation is dependent on NF-kappaB and MAP kinases. These mechanisms might help to explain the enhanced bone resorption associated with inflammatory disorders, including that in rheumatoid arthritis.

  • 36.
    Bremander, Ann
    et al.
    Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap, Bio- och miljösystemforskning (BLESS).
    Jacobsson, Lennart T. H.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Bergman, Stefan
    Research and Development Centre Spenshult, Halmstad, Sweden.
    Haglund, Emma
    Research and Development Centre Spenshult, Halmstad, Sweden.
    Petersson, Ingemar
    Department of Orthopedics, Clinical Sciences Lund, Lund University, Lund, Sweden.
    Smoking is Associated with Worse and More Widespread Pain, Worse Fatigue, General Health and Quality of Life in a Swedish population Based Cohort of Patients with Psoriatic Arthritis2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr S10, s. S777-S778, artikel-id 1828Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Purpose: Smoking has been found to be associated with an increased risk of developing psoriatic arthritis (PsA)1. The purpose of this study was analyse possible associations of smoking habits with self-reported clinical features in a large population based cohort of patients with a diagnosis of PsA.

    Methods: All health care seeking subjects with a diagnose of PsA according to ICD 10 codes (given at least once by a rheumatologist/internist or twice by any other physician) were identified by a regional health care register during 2003-20072. In 2009 all identified subjects aged 18 years or older (n=2003) were invited to participate in a cross sectional questionnaire survey. The questionnaire included self-reported data on smoking (never smokers or ever smokers), age at disease onset, physical function (HAQ, 0-3 best to worst), pain, fatigue and global health (numerical rating scales 0-10 best to worst) health related quality of life (EQ-5D, 0-1 worst to best), and number of painful regions noted on a pain mannequin (0-16, best to worst). Linear regression analysis was performed and all data were controlled for sex and age.

    Results: Response rate was 77% whereof 369 patients (18%) declined participation and 1185 (59%) returned the questionnaire,  mean age 57.5 (SD 13.5) years and 58% were women. 1173 subjects responded to the smoking question whereof 448 (38%) were never smokers and 725 (62%) were ever smokers.

    Mean age at disease onset was 42.3 (SD 13.4) years in never smokers vs. 46.0 (SD 13.2) in ever smokers. Never smokers vs. ever smokers had mean HAQ 0.59 (SD 0.6) vs. 0.71 (SD 0.6),  mean pain 3.9 (SD 2.4) vs.4.4 (SD 2.5),  mean fatigue 4.4 (SD 2.8) vs. 5.0 (SD 2.7),  mean global health 3.9 (SD 2.4) vs. 4.4 (SD 2.3), mean EQ-5D 0.68 (SD 0.23) vs. 0.63 (SD 0.26) and mean no of painful regions were 7.2 (SD 4.0) vs. 7.9 (SD 4.3).

    The regression analysis showed that ever smokers had worse pain with age-sex adjusted parameter estimates (B) = 0.38 (95% CI 0.09 ; 0.67), worse fatigue B = 0.34 (95% CI 0.02 ; 0.66), worse global health B = 0.36 (95% CI 0.09 ; 0.64), worse EQ-5D B = -0.04 (95% CI -0.07 ; -0.01) and an increased no of painful regions B = 0.54 (95% CI 0.02 ; 1.07) compared with never smokers.

    Conclusion: In this population based PsA cohort, patients who were ever smokers reported worse clinical features compared with never smokers. Further longitudinal studies are needed to better understand cause and effect. However, smoking cessation should be recommended due to general health perspectives and also due to disease specific issues.

  • 37.
    Bremander, Ann
    et al.
    Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap, Bio- och miljösystemforskning (BLESS), Biomekanik och biomedicin. Research and Development Centre, Spenshult Hospital for Rheumatic Diseases, Halmstad, Sweden.
    Petersson, Ingemar F.
    Department of Orthopedics, Clinical Sciences Lund, Lund University, Lund, Sweden.
    Haglund, Emma
    Spenshult Hospital for Rheumatic Diseases, Halmstad, Sweden.
    Bergman, Stefan
    Research and Development Centre, Spenshult Hospital for Rheumatic Diseases, Halmstad, Sweden.
    Jacobsson, Lennart T.H.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Smoking Is Associated with Worse and More Widespread Pain, Worse Disease Activity, Function, Fatigue and Health Related Quality of Life in Patients with Axial Spondyloarthritis: Results From a Population Based Cohort2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr S10, s. S43-S43, artikel-id 95Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In subjects with early axial Spondyloarthritis (SpA) smoking has recently been associated with earlier onset of disease, worse lesions of the sacroiliac joints and in later stages syndesmophyte progression. The aim was to study associations of smoking habits with self-reported information in a large population based cohort of patients with axial SpA.

    Methods: A cross-sectional questionnaire survey performed in 2009 included all health care seeking subjects aged >18 years with a diagnosis of SpA according to ICD 10 codes identified by a regional health care register (n=3711). Smoking habits were studied in patients with ankylosing spondylitis (AS, ICD M45) and in patients who fulfilled criteria for “non AS axial SpA” (without having one of AS). Criteria for non AS axial SpA were based on data from the questionnaire: pain for 3 months or more during the last 12 months together with 2 or more features out of 5 (inflammatory back pain, history of psoriasis, uveitis/tendinitis, inflammatory bowel disease or heredity). The questionnaire included data on smoking (never smokers vs. ever smokers), disease activity (BASDAI) physical function (BASFI), general health (BAS-G) all measured with numerical rating scales 0-10 (best to worst), health related quality of life (EQ-5D, 0-1 worst to best), pain, fatigue (numerical rating scales 0-10 best to worst) and number of painful regions noted on a pain mannequin (0-16 best to worst). Linear regression analysis was performed and all data were controlled for sex and age.

    Results:

    Response rate was 76% whereof 2167 (58%) returned the questionnaire and 18% declined participation in the study. 598 subjects had an AS diagnose and 572 fulfilled the criteria for non AS axial SpA.

    The AS group had a mean age of 54 (SD14) years and 35% were women. Never smokers constituted 48% of the AS group. Ever smokers had worse scores in all studied variables compared with never smokers.

    The linear regression analysis showed that ever smokers in the AS group had worse self-reported scores in BASDAI with age-sex adjusted parameter estimate (B) = 0.60 (95% CI 0.21 ; 1.00), BASFI B = 0.51 (95% CI 0.11 ; 0.91) and fatigue B = 0.51 (95% CI  0.06 ; 1.00) . There was a tendency to worse scores for ever smokers also in EQ-5D B = -0.04 (95% CI -0.09 ; 0.001)

    Mean age in the non AS axial SpA group was 55 (SD 14) years and 68% were women. Never smokers constituted 38% of this group. Also in the non AS axial SpA group the linear regression analysis showed that ever smokers had worse self-reported scores in BASDAI with age-sex adjusted parameter estimate (B) = 0.59 (95% CI 0.23 ; 0.94), BASFI B = 0.59 (95% CI 0.17 ; 1.00), pain B = 0.45 (95% CI 0.08 ; 0.82) and fatigue B = 0.43 (95% CI  0.03 ; 0.83), no of painful areas B = 0.73 (95% CI  0.06 ; 1.46) and also in EQ-5D B = -0.06 (95% CI -0.11 ; -0.002).                                                                                                                                                

    Conclusion: In a large population based axial SpA cohort, both patients with AS and non AS axial SpA who were ever smokers reported worse clinical features compared with never smokers. Further longitudinal studies are needed to better understand cause and effect. However, smoking cessation should be recommended not only due to general health perspectives but also due to disease specific issues.

    References

    1Smokers in early axial spondyloarthritis have earlier disease onset, more disease activity, inflammation and damage, and poorer function and health-related quality of life: results from the DESIR cohort. Chung HY, Machado P, van der Heijde D, D'Agostino MA, Dougados M. Ann Rheum Dis. 2012 Jun;71(6):809-16.

  • 38.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Bokarewa, Maria
    Erlandsson, Malin
    Rantapää-Dahlqvist, Solbritt M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Survivin But Not Fms-Like Tyrosine Kinase Ligand Is Up-Regulated Before Onset Of Rheumatoid Arthritis2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Special issue, Supplement 10, s. S589-S589, Meeting Abstract: 1393Artikel i tidskrift (Övrigt vetenskapligt)
  • 39. Brink, Mikael
    et al.
    Hansson, Monika
    Mathsson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Jakobsson, Per-Johan
    Holmdahl, Rikard
    Hallmans, Goran
    Stenlund, Hans
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Klareskog, Lars
    Rantapaa-Dahlqvist, Solbritt
    Multiplex Analyses of Antibodies Against Citrullinated Peptides in Individuals Prior to Development of Rheumatoid Arthritis2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr 4, s. 899-910Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective The presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the onset of symptoms of rheumatoid arthritis (RA) by several years. The aim of this study was to analyze antibodies against 10 citrullinated autoantigen-derived peptides for reactivity before the onset of RA symptoms. Methods A casecontrol study was conducted within the Medical Biobank of Northern Sweden. The study was performed in 409 individuals, 386 of whom donated 717 blood samples before the onset of symptoms of RA (pre-patients). The median period of time predating the onset of RA was 7.4 years. A total of 1,305 population-based control subjects were also studied. Antibodies to 10 citrullinated peptides, fibrinogen 573 (Fib573), Fib591, Fib3652, Fib72, Fib74, -enolase (citrullinated -enolase peptide 1 [CEP-1]), triple-helical type II collagen peptide C1 (citC1III), filaggrin, vimentin 217 (Vim217), and Vim6075, were analyzed using a microarray system. Results The fluorescence intensity of antibodies against Fib3652, Fib74, CEP-1, citC1III, and filaggrin was significantly increased in pre-patients compared with controls (P < 0.001). The levels of the earliest-detectable antibodies (Fib591 and Vim6075) fluctuated over time, with only a slight increase after the onset of disease. The frequency of antibodies against Fib3652, CEP-1, and filaggrin increased gradually, reaching the highest levels before symptom onset. The frequency of a cluster of antibodies, citC1III, Fib573, and Fib74, increased only slightly before the onset of symptoms but increased prominently after disease onset. The odds ratio for the development of RA in individuals expressing both CEP-1 and Fib3652 antibodies (using data from samples obtained <3.35 years predating symptom onset) was 40.4 (95% confidence interval 19.882.3) compared with having either antibody alone. Conclusion Development of an immune response toward citrullinated peptides is initially restricted but expands with time to induce a more specific response, with levels, particularly those of antibodies against CEP-1, Fib3652, and filaggrin, increasing during the predating time period closer to the onset of symptoms.

  • 40.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hansson, Monika
    Mathsson, Linda
    Jakobsson, Per-Johan
    Holmdahl, Rikard
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Rönnelid, Johan
    Klareskog, Lars
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr 4, s. 899-910Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: The presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the symptom onset of rheumatoid arthritis (RA) by several years. Antibodies against 10 citrullinated autoantigen-derived peptides were analysed for reactivity before onset of symptoms. METHODS: In the Medical Biobank of Northern Sweden 409 individuals were identified, of whom 386 provided 717 samples, obtained before onset of symptoms of RA (median time 7.4 (IQR 9.3) years); 1305 population based controls were also identified. Antibodies to 10 citrullinated peptides; fibrinogen (Fib) Fibα573, Fibα591, Fibß36-52, Fibß72, Fibß74, α-enolase (CEP-1), Type II Collagen citC1(III) , filaggrin, vimentin (Vim)2-17, and Vim60-75 were analysed using a microarray system. RESULTS: The antibody fluorescence intensity of Fibß36-52, Fibß74, CEP-1, citC1(III) , and filaggrin was significantly increased in pre-disease individuals compared with controls (p<0.001). The levels of the earliest detectable antibodies (Fibα591 and Vim60-75) fluctuated over time, with only a slight increase after onset of disease. Antibodies against Fibß36-52, CEP-1 and filaggrin increased gradually reaching the highest levels of all antibodies before symptom onset. A cluster of antibodies, citC1(III) , Fibα573 and Fibß74 increased only slightly before onset of symptoms but prominently after disease onset. The odds ratio for development of RA with a combination of CEP-1 and Fibß36-52 antibodies (<3.35 years pre-dating) was 38.8 (CI95%14.5-103.5) compared with having either. CONCLUSION: Development of an immune response towards citrullinated peptides is initially restricted but expands with time to induce a more specific response with increasing levels towards onset of symptoms, particularly invoving antibodies against CEP-1, Fibß36-52 and filaggrin.

  • 41.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lejon, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    B-Regulatory-, CD19(+)CD20(+) CD24(high)CD38(high) -Cells Are Functionally Impaired In Patients With Rheumatoid Arthritis and Healthy First Degree Relatives Compared With Controls2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Special issue, Supplement 10, s. S393-S394, Meeting Abstract: 917Artikel i tidskrift (Övrigt vetenskapligt)
  • 42.
    Brodin, N.
    et al.
    Karolinska Institutet, Stockholm, Sweden, Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, 23100, SE-14183 Huddinge, Sweden.
    Eurenius, E.
    Karolinska Institutet, Stockholm, Sweden.
    Jensen, I.
    Karolinska Institutet, Stockholm, Sweden.
    Nisell, R.
    Karolinska Institutet, Stockholm, Sweden.
    Opava, C.H.
    Karolinska Institutet, Stockholm, Sweden.
    Algebrandt, M.
    Linköping University Hospital, Linköping, Sweden.
    Almin, I.
    Örebro University Hospital, Örebro, Sweden.
    Andersson, B.
    Karolinska University Hospital-Solna, Stockholm, Sweden.
    Bertholds, G.
    Skövde Hospital, Skövde, Sweden.
    Forsberg, C.
    Falun Hospital, Falun, Sweden.
    Haglund, E.
    Spenshult AB, Oskarström, Sweden.
    Holmen-Andersson, A.-M.
    Holmén-Andersson, A.-M., Sahlgrenska University Hospital, Mölndal, Sweden.
    Hultman, A.
    Uppsala University Hospital, Uppsala, Sweden.
    Lennartsson, C.
    Karolinska University Hospital-Huddinge, Stockholm, Sweden.
    Norman, E.
    Danderyd Hospital, Stockholm, Sweden.
    Coaching patients with early rheumatoid arthritis to healthy physical activity: A multicenter, randomized, controlled study2008Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 59, nr 3, s. 325-331Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To investigate the effect of a 1-year coaching program for healthy physical activity on perceived health status, body function, and activity limitation in patients with early rheumatoid arthritis. Methods. A total of 228 patients (169 women, 59 men, mean age 55 years, mean time since diagnosis 21 months) were randomized to 2 groups after assessments with the EuroQol visual analog scale (VAS), Grippit, Timed-Stands Test, Escola Paulista de Medicina Range of Motion scale, walking in a figure-of-8, a visual analog scale for pain, the Health Assessment Questionnaire disability index, a self-reported physical activity questionnaire, and the Disease Activity Score in 28 joints. All patients were regularly seen by rheumatologists and underwent rehabilitation as prescribed. Those in the intervention group were further individually coached by a physical therapist to reach or maintain healthy physical activity (=30 minutes, moderately intensive activity, most days of the week). Results. The retention rates after 1 year were 82% in the intervention group and 85% in the control group. The percentages of individuals in the intervention and control groups fulfilling the requirements for healthy physical activity were similar before (47% versus 51%, P > 0.05) and after (54% versus 44%, P > 0.05) the intervention. Analyses of outcome variables indicated improvements in the intervention group over the control group in the EuroQol VAS (P = 0.025) and muscle strength (Timed-Stands Test, P = 0.000) (Grippit, P = 0.003), but not in any other variables assessed. Conclusion. A 1-year coaching program for healthy physical activity resulted in improved perceived health status and muscle strength, but the mechanisms remain unclear, as self-reported physical activity at healthy level did not change. © 2008, American College of Rheumatology.

  • 43.
    Brodin, Nina
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Eurenius, Eva
    Karolinska Institutet, Stockholm, Sweden.
    Jensen, Irene
    Karolinska Institutet, Stockholm, Sweden.
    Nisell, Ralph
    Karolinska Institutet, Stockholm, Sweden.
    Opava, Christina H.
    Karolinska Institutet, Stockholm, Sweden.
    Almin, Ingrid
    Örebro University Hospital, Örebro, Sweden.
    Andersson, Britt
    Karolinska University Hospital–Solna, Stockholm, Sweden.
    Bertholds, Gunhild
    Skövde Hospital, Skövde, Sweden.
    Forsberg, Catarina
    Falun Hospital, Falun, Sweden.
    Haglund, Emma
    Spenshult AB, Oskarström, Sweden.
    Holmén-Andersson, Ann-Marie
    Sahlgrenska University Hospital, Mölndal, Sweden.
    Hultman, Anna
    Uppsala University Hospital, Uppsala, Sweden.
    Lennartsson, Claudia
    Karolinska University Hospital–Huddinge, Stockholm, Sweden.
    Norman, Elin
    Danderyd Hospital, Stockholm, Sweden.
    Coaching Patients With Early Rheumatoid Arthritis to Healthy Physical Activity: A Multicenter, Randomized, Controlled Study2008Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 59, nr 3, s. 325-331Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    To investigate the effect of a 1-year coaching program for healthy physical activity on perceived health status, body function, and activity limitation in patients with early rheumatoid arthritis.

    Methods

    A total of 228 patients (169 women, 59 men, mean age 55 years, mean time since diagnosis 21 months) were randomized to 2 groups after assessments with the EuroQol visual analog scale (VAS), Grippit, Timed-Stands Test, Escola Paulista de Medicina Range of Motion scale, walking in a figure-of-8, a visual analog scale for pain, the Health Assessment Questionnaire disability index, a self-reported physical activity questionnaire, and the Disease Activity Score in 28 joints. All patients were regularly seen by rheumatologists and underwent rehabilitation as prescribed. Those in the intervention group were further individually coached by a physical therapist to reach or maintain healthy physical activity (≥30 minutes, moderately intensive activity, most days of the week).

    Results

    The retention rates after 1 year were 82% in the intervention group and 85% in the control group. The percentages of individuals in the intervention and control groups fulfilling the requirements for healthy physical activity were similar before (47% versus 51%; P > 0.05) and after (54% versus 44%; P > 0.05) the intervention. Analyses of outcome variables indicated improvements in the intervention group over the control group in the EuroQol VAS (P = 0.025) and muscle strength (Timed-Stands Test; P = 0.000) (Grippit; P = 0.003), but not in any other variables assessed.

    Conclusion

    A 1-year coaching program for healthy physical activity resulted in improved perceived health status and muscle strength, but the mechanisms remain unclear, as self-reported physical activity at healthy level did not change. © 2008, American College of Rheumatology.

  • 44. Brodin, Nina
    et al.
    Eurenius, Eva
    Verksamhetsutvecklingsstaben - Vård och hälsa, Västerbottens läns landsting.
    Jensen, Irene
    Nisell, Ralph
    Opava, Christina H
    Coaching patients with early rheumatoid arthritis to healthy physical activity: a multicenter, randomized, controlled study2008Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 59, nr 3, s. 325-331Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate the effect of a 1-year coaching program for healthy physical activity on perceived health status, body function, and activity limitation in patients with early rheumatoid arthritis.

    METHODS: A total of 228 patients (169 women, 59 men, mean age 55 years, mean time since diagnosis 21 months) were randomized to 2 groups after assessments with the EuroQol visual analog scale (VAS), Grippit, Timed-Stands Test, Escola Paulista de Medicina Range of Motion scale, walking in a figure-of-8, a visual analog scale for pain, the Health Assessment Questionnaire disability index, a self-reported physical activity questionnaire, and the Disease Activity Score in 28 joints. All patients were regularly seen by rheumatologists and underwent rehabilitation as prescribed. Those in the intervention group were further individually coached by a physical therapist to reach or maintain healthy physical activity (> or =30 minutes, moderately intensive activity, most days of the week).

    RESULTS: The retention rates after 1 year were 82% in the intervention group and 85% in the control group. The percentages of individuals in the intervention and control groups fulfilling the requirements for healthy physical activity were similar before (47% versus 51%; P > 0.05) and after (54% versus 44%; P > 0.05) the intervention. Analyses of outcome variables indicated improvements in the intervention group over the control group in the EuroQol VAS (P = 0.025) and muscle strength (Timed-Stands Test; P = 0.000) (Grippit; P = 0.003), but not in any other variables assessed.

    CONCLUSION: A 1-year coaching program for healthy physical activity resulted in improved perceived health status and muscle strength, but the mechanisms remain unclear, as self-reported physical activity at healthy level did not change.

  • 45.
    Båve, Ullvi
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lövgren, Tanja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Cajander, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eloranta, Maija-Leena
    Alm, Gunnar V.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Activation of the type I interferon system in primary Sjögren's syndrome: a possible etiopathogenic mechanism2005Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 52, nr 4, s. 1185-1195Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    The etiopathogenesis of primary Sjögren's syndrome (SS) is largely unknown. In other autoimmune diseases, type I interferon (IFN) may play a pivotal role by triggering and sustaining the disease process. We therefore aimed to determine whether patients with primary SS had an activated type I IFN system.

    Methods

    Salivary gland biopsy specimens and sera from patients with primary SS were investigated for the occurrence of IFNα-producing cells and measurable IFNα levels, respectively. The ability of primary SS sera together with apoptotic or necrotic cells to induce IFNα production in normal peripheral blood mononuclear cells was examined. The IFNα inducer was characterized, and IFNα-producing cells were identified. Clinical data were correlated with the IFNα-inducing capacity of primary SS sera.

    Results

    Numerous IFNα-producing cells were detected in salivary gland biopsy specimens, despite low serum IFNα levels. Autoantibodies to RNA-binding proteins, combined with material released by necrotic or late apoptotic cells, were potent inducers of IFNα production in plasmacytoid dendritic cells (PDCs). This appeared to be attributable to RNA-containing immune complexes triggering PDCs by means of RNA and interaction with Fcγ receptor IIa. The IFNα-inducing capacity of sera was associated with positive results of a labial salivary gland biopsy (focus score ≥1) and with dermatologic, hematologic, and pulmonary manifestations.

    Conclusion

    Patients with primary SS have an activated type I IFN system. Although virus may initiate the production of IFN, the continued IFNα synthesis is caused by RNA-containing immune complexes that activate PDCs to prolong IFNα production at the tissue level. This IFNα promotes the autoimmune process by a vicious circle–like mechanism, with increased autoantibody production and formation of more endogenous IFNα inducers.

  • 46. Cerqueira, Catia
    et al.
    Ossipova, Elena
    Hansson, Monika
    Mathsson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Klareskog, Lars
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Jakobsson, Per Johan
    Neutralization Of Anti-Citrullinated Protein Antibodies - a Way To Go?2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Suppl. 10, s. S391-S392Artikel i tidskrift (Övrigt vetenskapligt)
  • 47. Chatzidionysiou, Katerina
    et al.
    Turesson, Carl
    Teleman, Annika
    Knight, Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Lindqvist, Elisabet
    Larsson, Per
    Coster, Lars
    Rydberg, Barbro
    van Vollenhoven, Ronald F.
    Heimburger, Mikael
    A Multicenter, Randomized, Controlled, Open-Label Pilot Study of the Feasibility of Discontinuation of Adalimumab in Rheumatoid Arthritis Patients in Stable Clinical Remission2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr S10, s. S336-S336Artikel i tidskrift (Övrigt vetenskapligt)
  • 48. Chung, Sharon A
    et al.
    Tian, Chao
    Taylor, Kimberly E
    Lee, Annette T
    Ortmann, Ward A
    Hom, Geoffrey
    Graham, Robert R
    Nititham, Joanne
    Kelly, Jennifer A
    Morrisey, Jean
    Wu, Hui
    Yin, Hong
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Alarcón-Riquelme, Marta E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Tsao, Betty P
    Harley, John B
    Gaffney, Patrick M
    Moser, Kathy L
    Manzi, Susan
    Petri, Michelle
    Gregersen, Peter K
    Langefeld, Carl D
    Behrens, Timothy W
    Seldin, Michael F
    Criswell, Lindsey A
    European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus2009Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, nr 8, s. 2448-2456Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To determine whether genetic substructure in European-derived populations is associated with specific manifestations of systemic lupus erythematosus (SLE), including mucocutaneous phenotypes, autoantibody production, and renal disease. METHODS: SLE patients of European descent (n=1,754) from 8 case collections were genotyped for >1,400 ancestry informative markers that define a north-south gradient of European substructure. Using the Structure program, each SLE patient was characterized in terms of percent Northern (versus percent Southern) European ancestry based on these genetic markers. Nonparametric methods, including tests for trend, were used to identify associations between Northern European ancestry and specific SLE manifestations. RESULTS: In multivariate analyses, increasing levels of Northern European ancestry were significantly associated with photosensitivity (Ptrend=0.0021, odds ratio for highest quartile of Northern European ancestry versus lowest quartile [ORhigh-low] 1.64, 95% confidence interval [95% CI] 1.13-2.35) and discoid rash (Ptrend=0.014, ORhigh-low 1.93, 95% CI 0.98-3.83). In contrast, increasing levels of Northern European ancestry had a protective effect against the production of anticardiolipin autoantibodies (Ptrend=1.6x10(-4), ORhigh-low 0.46, 95% CI 0.30-0.69) and anti-double-stranded DNA autoantibodies (Ptrend=0.017, ORhigh-low 0.67, 95% CI 0.46-0.96). CONCLUSION: This study demonstrates that specific SLE manifestations vary according to Northern versus Southern European ancestry. Thus, genetic ancestry may contribute to the clinical heterogeneity and variation in disease outcomes among SLE patients of European descent. Moreover, these results suggest that genetic studies of SLE subphenotypes will need to carefully address issues of population substructure based on genetic ancestry.

  • 49.
    Classen, Jean-Francois
    et al.
    de Duve Institute, Universite´ Catholique de Louvain, Brussels, Belgium.
    Henrohn, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lennartsson, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Lauwerys, Bernard R.
    Saint-Luc University Hospital, Universite´ Catholique de Louvain, Brussels, Belgium.
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rorsman, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Lenglez, Sandrine
    de Duve Institute, Universite´ Catholique de Louvain, Brussels, Belgium.
    Franck-Larsson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Tomasi, Jean-Paul
    Saint-Luc University Hospital, Universite´ Catholique de Louvain, Brussels, Belgium.
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vanthuyne, Marie
    Saint-Luc University Hospital, Universite´ Catholique de Louvain, Brussels, Belgium.
    Houssiau, Frédéric A.
    Saint-Luc University Hospital, Universite´ Catholique de Louvain, Brussels, Belgium.
    Demoulin, Jean-Baptiste
    de Duve Institute, Universite´ Catholique de Louvain, Brussels, Belgium.
    Lack of evidence of stimulatory autoantibodies to platelet-derived growth factor receptor in patients with systemic sclerosis2009Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, nr 4, s. 1137-1144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Systemic sclerosis (SSc) is a severe connective tissue disease of unknown etiology, characterized by fibrosis of the skin and multiple internal organs. Recent findings suggested that the disease is driven by stimulatory autoantibodies to platelet-derived growth factor receptor (PDGFR), which stimulate the production of reactive oxygen species (ROS) and collagen by fibroblasts. These results opened novel avenues of research into the diagnosis and treatment of SSc. The present study was undertaken to confirm the presence of anti-PDGFR antibodies in patients with SSc. METHODS: Immunoglobulins from 37 patients with SSc were purified by protein A/G chromatography. PDGFR activation was tested using 4 different sensitive bioassays, i.e., cell proliferation, ROS production, signal transduction, and receptor phosphorylation; the latter was also tested in a separate population of 7 patients with SSc from a different research center. RESULTS: Purified IgG samples from patients with SSc were positive when tested for antinuclear autoantibodies, but did not specifically activate PDGFRalpha or PDGFRbeta in any of the tests. Cell stimulation with PDGF itself consistently produced a strong signal. CONCLUSION: The present results raise questions regarding the existence of agonistic autoantibodies to PDGFR in SSc.

  • 50. Dahlqvist, Solbritt Rantapää
    et al.
    Arlestig, L
    Sikstrom, C
    Linghult, S
    Tumor necrosis factor receptor type II (exon 6) and interleukin-6 (-174) gene polymorphisms are not associated with family history but tumor necrosis factor receptor type II is associated with hypertension in patients with rheumatoid arthritis from northern Sweden2002Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 46, s. 3096-3098Artikel i tidskrift (Refereegranskat)
1234 1 - 50 av 187
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf