Ändra sökning
Avgränsa sökresultatet
1617181920 901 - 950 av 987
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.
  • 901. Verheul, Marije K.
    et al.
    Böhringer, Stefan
    van Delft, Myrthe A. M.
    Jones, Jonathan D.
    Rigby, William F. C.
    Gan, Ryan W.
    Holers, V. Michael
    Edison, Jess D.
    Deane, Kevin D.
    Janssen, Koen M. J.
    Westra, Johanna
    Brink, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Huizinga, Tom W. J.
    van der Helm-van Mil, Annette H. M.
    van der Woude, Diane
    Toes, Rene E. M.
    Trouw, Leendert A.
    Triple positivity for anti–citrullinated protein autoantibodies, rheumatoid factor, and anti–carbamylated protein antibodies conferring high specificity for rheumatoid arthritis: implications for very early identification of at‐risk individuals2018Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70, nr 11, s. 1721-1731Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: In rheumatoid arthritis(RA), the autoantibodies anti-citrullinated protein antibodies(ACPA) and rheumatoid factor(RF) are commonly used to aid RA diagnosis. Although these autoantibodies are mainly found in RA, their specificity is not optimal. It is therefore difficult to identify RA patients, especially in very early disease, based on the presence of ACPA and RF alone. Also, anti-carbamylated protein(anti-CarP) antibodies have diagnostic and prognostic value as the presence of anti-CarP antibodies associates with joint damage in RA patients and with future RA development in arthralgia patients. Therefore, we aimed to investigate the value of combined antibody testing in relation to prediction and diagnosis of (early) RA.

    METHODS: A literature search resulted in twelve studies, consisting of RA patients, pre-RA individuals, disease controls, healthy first-degree relatives of RA patients or healthy controls, in which data on RF, ACPA and anti-CarP antibody-status was available. Random effects meta-analyses were carried out for several antibody combinations.

    RESULTS: The individual antibodies are highly prevalent in RA(34%-80%) compared to the control groups, but are also present in non-RA controls(0%-23%). To classify most people correctly as RA or non-RA, the combination of ACPA and/or RF often performs well(specificity:65-100, sensitivity:59-88). However, triple positivity for ACPA, RF and anti-CarP antibodies results in a higher specificity(98-100) (accompanied by a lower sensitivity(11-39)).

    CONCLUSIONS: As the rheumatology field is moving towards very early identification of RA and possible screening for individuals at maximum risk in populations with a low pre-test probability, triple positivity provides interesting information on individuals at risk to develop RA.

  • 902. Vikerfors, Anna
    et al.
    Johansson, Anna-Britta
    Gustafsson, Johanna T
    Jönsen, Andreas
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Zickert, Agneta
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Sturfelt, Gunnar
    Bengtsson, Anders
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Gunnarsson, Iva
    Elvin, Kerstin
    Svenungsson, Elisabet
    Clinical manifestations and anti-phospholipid antibodies in 712 patients with systemic lupus erythematosus: evaluation of two diagnostic assays2013Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 34, nr 5, s. 345-353Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives

    To evaluate the agreement and performance of two tests for aPLs with regard to association with manifestations of the APS in patients with SLE.

    Methods

    We investigated 712 SLE patients and 280 population controls. Cardiolipin and β2 glycoprotein-I antibodies were measured with routine ELISA and a new automated method. Three positivity cut-offs (99%, 90% of controls and recommended cut-off by manufacturers) were used. Associations with previous thrombotic events, thrombocytopenia and, in a subgroup of patients, obstetric morbidity (n = 296) were evaluated. Results were compared with the LA test, performed in 380 patients.

    Results

    Inter-test agreement was moderate (demonstrated by κ-values 0.16–0.71). Performance of the two tests was similar: at the 99th percentile cut-off, sensitivity for any thrombotic event ranged from 3.7% to 24.8%, while specificity was 84.7–97.7%. Regardless of assay, IgG isotypes were associated with venous thrombosis and ischaemic cerebrovascular disease, whereas aPLs of IgM isotype were weakly associated with ischaemic heart disease. Associations were greatly affected by aPL level. LA performed better than the specific aPL tests. LA was associated with any thrombotic event, odds ratio 5.4 (95% CI 3.1, 9.4), while the specific aPL tests ranged from non-significant to an odds ratio of 1.9 (95% CI 1.03, 3.4) using criteria cut-off. LA was also convincingly associated with other APS manifestations.

    Conclusion

    In relation to thrombotic manifestations, there was moderate agreement but no clear advantages when comparing a routine aPL ELISA with an automated method. APL isotype and titre as well as LA positivity are important for risk assessment in SLE patients.

  • 903. Virkki, Liisa M
    et al.
    Porola, Pauliina
    Forsblad-d'Elia, Helena
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Valtysdottir, Sigridur
    Solovieva, Svetlana A
    Konttinen, Yrjö T
    Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjögren's syndrome.2010Ingår i: Arthritis care & research, ISSN 2151-4658, Vol. 62, nr 1, s. 118-24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Primary Sjögren's syndrome (SS) is characterized by fatigue and low levels of serum dehydroepiandrosterone/dehydroepiandrosterone sulfate (DHEA/DHEAS). Our aim was to study whether SS patients with severe fatigue and low serum DHEAS values benefit from DHEA substitution (50 mg/day).

    METHODS: A multicenter, investigator-based, powered, randomized controlled clinical trial (crossover, washout design) using fatigue as the primary outcome measure was performed on patients with primary SS (n = 107) who had a general fatigue score > or =14 on the 20-item Multiple Fatigue Inventory (MFI-20), combined with age- and sex-adjusted serum DHEAS values below the mean. Fatigue was assessed using MFI-20 subscales, i.e., general fatigue, physical fatigue, mental fatigue, reduced motivation, and activity (scale 4-20), and with a visual analog scale (VAS; scale 0-100).

    RESULTS: In an intent-to-treat analysis, a 50-mg DHEA substitution dose and placebo similarly improved fatigue. All of the MFI-20 subscales and the fatigue VAS improved from the baseline levels as a result of treatment (P < 0.001), but with negligible differences between these 2 treatments. The mean between-treatment difference was -0.1 for general fatigue (the primary outcome measure), 0.0 for physical fatigue, 0.0 for mental fatigue, 0.0 for reduced motivation, 0.3 for reduced activity, and 2.2 for the fatigue VAS. None of these differences was statistically significant.

    CONCLUSION: Similar to earlier results using pharmacologic doses, substitution treatment with 50 mg of DHEA in DHEA-deficient and severely tired primary SS patients does not help against fatigue better than placebo. This may relate to the prohormone nature of DHEA and its recently described defective intracrine tissue-specific conversion to active sex steroids in SS.

  • 904.
    Vultaggio, A.
    et al.
    Careggi Univ Hosp, Dept Biomed, Immunoallergol Unit, Florence, Italy.
    Nencini, F.
    Univ Florence, Ctr Res Transfer & High Educ DENOTHE, Florence, Italy;Univ Florence, Dept Expt & Clin Med, Florence, Italy.
    Carraresi, A.
    Careggi Univ Hosp, Dept Biomed, Immunoallergol Unit, Florence, Italy.
    Pratesi, S.
    Univ Florence, Ctr Res Transfer & High Educ DENOTHE, Florence, Italy;Univ Florence, Dept Expt & Clin Med, Florence, Italy.
    Movérare, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning. Thermo Fisher Sci, ImmunoDiagnost, Uppsala, Sweden.
    Eriksson, C.
    Thermo Fisher Sci, ImmunoDiagnost, Uppsala, Sweden.
    Venemalm, L.
    Thermo Fisher Sci, ImmunoDiagnost, Uppsala, Sweden.
    Maggi, E.
    Univ Florence, Ctr Res Transfer & High Educ DENOTHE, Florence, Italy;Univ Florence, Dept Expt & Clin Med, Florence, Italy.
    Matucci, A.
    Careggi Univ Hosp, Dept Biomed, Immunoallergol Unit, Florence, Italy.
    IgG4 anti-infliximab in treated patients: Clinical impact and temporal evolution2018Ingår i: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 73, nr 11, s. 2172-2181Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Infliximab (IFX) carries potential risk of immunogenicity with the production of anti-drug antibodies (ADA). ADA may belong to different isotypes and are usually measured by ELISA bridging assay. This test is not designed to detect IgG4 antibodies. The aim was to measure IgG4 anti-IFX antibodies in a cohort of IFX-treated patients and to evaluate their relationship with ADA and their clinical impact.

    Methods: Anti-drug antibodies were detected using a bridging ELISA in the serum of 222 treated patients with different clinical outcomes to IFX. The same samples were analyzed for IgG4 anti-IFX antibodies using an experimental ImmunoCAP assay with reduced serum IgG4 background levels. A longitudinal evaluation was performed in a subgroup of 38 patients to define the temporal evolution of IgG4 anti-IFX.

    Results: IgG4 anti-IFX was found in 26.6% of patients. Eighty of 222 patients were ADA+ (36%) and the majority (57/80, 71.3%) had IgG4 anti-IFX. Two IgG4-positive but ADA-negative patients were identified. IgG4 anti-IFX levels correlated with the serum levels of ADA. IgG4 anti-IFX was more common in both reactive and nonresponder patients than in tolerant/responder patients. Patients who had experienced IgE-mediated reactions displayed significantly higher IgG4 anti-IFX than IgE-negative reactive patients. The majority of patients tested positive for IgG4 anti-IFX after the first seven infusions.

    Conclusions: IgG4 anti-IFX is common in treated patients and a large part of ADA producing patients produce IgG4 antibodies. The IgG4 anti-IFX response does not prevent hypersensitivity reactions to IFX and correlates with the IgE anti-IFX response.

  • 905. Wadström, H
    et al.
    Eriksson, J K
    Neovius, M
    Askling, J
    How good is the coverage and how accurate are exposure data in the Swedish Biologics Register (ARTIS)?2015Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To assess the coverage of the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden, ARTIS) across indications, and the accuracy of the registered information on treatment with biologics.

    METHOD: Through cross-reference of ARTIS to almost complete national health registers on prescriptions (adalimumab and etanercept), outpatient visits, and death/residency during 2008-2010, we assessed: the treatment coverage of ARTIS for each treatment indication, the validity of the registered start and stop dates, ARTIS treatments with no corresponding drug dispensations, and the accuracy of the registered information on concomitant anti-rheumatic therapies.

    RESULTS: According to the national health registers, 3945 individuals with a spondyloarthropathy (SpA) and 8032 patients with rheumatoid arthritis (RA) had filled at least one adalimumab or etanercept prescription during the study period. Of these, 86% of those with SpAs and 95% of patients with RA were also found in ARTIS with the corresponding treatment. Tumour necrosis factor (TNF) inhibitor prescriptions had been filled by 95% of patients between the ARTIS start and stop dates (allowing a 90-day window). More than 60 days before and more than 60 days after the registered start date in ARTIS, 5% and 4% respectively of patients had filled their first TNF inhibitor prescription. More than 90 days after the registered stop date in ARTIS, 8% of patients had filled one or more TNF inhibitor prescriptions.

    CONCLUSIONS: We observed a high coverage and accuracy of ARTIS data on biologics exposure, for both SpAs and RA. The combination of data from clinical registers such as ARTIS with data from national health registers offers a high quality measurement of actual treatment.

  • 906. Wadström, H
    et al.
    Eriksson, J K
    Neovius, M
    Askling, J
    Baecklund, Eva
    How good is the coverage and how accurate are exposure data in the Swedish Biologics Register (ARTIS)?2015Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To assess the coverage of the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden, ARTIS) across indications, and the accuracy of the registered information on treatment with biologics.

    METHOD: Through cross-reference of ARTIS to almost complete national health registers on prescriptions (adalimumab and etanercept), outpatient visits, and death/residency during 2008-2010, we assessed: the treatment coverage of ARTIS for each treatment indication, the validity of the registered start and stop dates, ARTIS treatments with no corresponding drug dispensations, and the accuracy of the registered information on concomitant anti-rheumatic therapies.

    RESULTS: According to the national health registers, 3945 individuals with a spondyloarthropathy (SpA) and 8032 patients with rheumatoid arthritis (RA) had filled at least one adalimumab or etanercept prescription during the study period. Of these, 86% of those with SpAs and 95% of patients with RA were also found in ARTIS with the corresponding treatment. Tumour necrosis factor (TNF) inhibitor prescriptions had been filled by 95% of patients between the ARTIS start and stop dates (allowing a 90-day window). More than 60 days before and more than 60 days after the registered start date in ARTIS, 5% and 4% respectively of patients had filled their first TNF inhibitor prescription. More than 90 days after the registered stop date in ARTIS, 8% of patients had filled one or more TNF inhibitor prescriptions.

    CONCLUSIONS: We observed a high coverage and accuracy of ARTIS data on biologics exposure, for both SpAs and RA. The combination of data from clinical registers such as ARTIS with data from national health registers offers a high quality measurement of actual treatment.

  • 907.
    Wadström, Hjalmar
    et al.
    Department of Medicine Solna, Karolinska Institutet, Stockholm .
    Arkema, Elizabeth V
    Department of Medicine Solna, Karolinska Institutet, Stockholm.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland. Linköpings universitet, Medicinska fakulteten.
    Askling, Johan
    Department of Medicine Solna, Karolinska Institutet, Stockholm.
    Simard, Julia F
    Department of Medicine Solna, Karolinska Institutet, Stockholm, Department of Health Research and Policy, Department of Medicine, Stanford School of Medicine, Stanford, CA, USA.
    Cervical neoplasia in systemic lupus erythematosus: a nationwide study.2017Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56, nr 4, s. 613-619Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim was to examine the risk of cervical neoplasia in women with SLE, overall and with respect to treatment, compared with women from the general population.

    METHODS: By linking national Swedish registers, we assembled a cohort including women with SLE (n = 4976) and matched general population comparators (n = 29 703). Two subcohorts of treated SLE patients were defined on the basis of treatment with antimalarials (n = 1942) and other immunosuppressants (AZA, CYC, ciclosporin, MTX, MMF or rituximab; n = 2175). The main outcome was defined as a first cervical neoplasia (dysplasia or cancer) during follow-up. Secondary outcomes were first cervical intraepithelial neoplasia (CIN) 1; first CIN grades 2-3; and first invasive cervical cancer during follow-up (2006-12). Cox regression models estimated relative risks adjusted for age, level of education, health-care utilization, number of children, marital status, family history of cervical cancer and prior cervical screening.

    RESULTS: Based on 121 events of cervical neoplasia during 23 136 person-years among SLE patients, there was an increased risk of any cervical neoplasia compared with the general population [hazard ratio (HR) = 2.12 (95% CI: 1.65, 2.71)]. The risk of CIN 1 [HR = 2.33 (95% CI: 1.58, 3.44)], CIN 2-3 [HR = 1.95 (95% CI: 1.43, 2.65)], but not invasive cervical cancer [HR = 1.64 (95% CI: 0.54, 5.02)], was increased in women with SLE. The subcohort treated with other immunosuppressants was at highest risk of cervical neoplasia.

    CONCLUSION: SLE is a risk factor for cervical neoplasia, in particular for pre-malignant cervical lesions. Among patients with SLE, the risk is higher among those treated with immunosuppresants compared with those treated with antimalarials.

  • 908. Wadström, Hjalmar
    et al.
    Frisell, Thomas
    Sparén, Pär
    Askling, Johan
    Do RA or TNF inhibitors increase the risk of cervical neoplasia or of recurrence of previous neoplasia? A nationwide study from Sweden.2016Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To examine screening patterns and the risk of cervical neoplasia in women with rheumatoid arthritis (RA) treated or not with tumour necrosis factor inhibitors (TNFi).

    METHODS: We performed a nationwide register-based cohort study in Sweden of women with RA who started a first TNFi (n=9629), biologics-naive women with RA (n=34 984) and general population comparators (matched 1:10, n=300 331), followed up from 1999 to 2012. Outcomes were first cytology screening with normal outcome, first ever cervical intraepithelial neoplasia (CIN) grade 1, first ever CIN 2-3 or adenocarcinoma in situ and first ever invasive cervical cancer during follow-up. HRs were assessed through Cox regressions adjusted for age, educational level, prior cervical screens, comorbidities, marital status and prior hospitalisations.

    RESULTS: Biologic-naive women with RA had more screenings (HR 1.08, 95% CI 1.06 to 1.10), were at greater risk of CIN 1 (HR 1.53, 1.23 to 1.89) and CIN 2-3 (HR 1.39, 1.16 to 1.66), but not of invasive cervical cancer (HR 1.09, 0.71 to 1.65) compared with the general population. Patients who initiated TNFi therapy had similar screening patterns (HR 1.01, 0.98 to 1.05), were not at increased risk of CIN 1 (HR 1.23, 0.87 to 1.74), but were at increased risk of CIN 2-3 (HR 1.36, 1.01 to 1.82) and invasive cervical cancer (HR 2.10, 1.04 to 4.23) compared with biologics-naive women with RA. Estimates varied little with successive adjustments, but were attenuated/absent in sensitivity analyses restricted to 2006-2012 and a disease-modifying antirheumatic drugs-treated comparator.

    CONCLUSIONS: Women with RA in general are at elevated risk of cervical dysplasia. Compared with biologics-naive patients, women treated with TNFi are at increased risk of cervical cancer. Whether this increase is causally linked with TNFi could not be fully disentangled.

  • 909.
    Waehrens, Eva
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Bliddal, H.
    Danneskiold-Samsoe, B.
    Lund, H.
    Fisher, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Differences between questionnaire- and interview-based measures of activities of daily living (ADL) ability and their association with observed ADL ability in women with rheumatoid arthritis, knee osteoarthritis, and fibromyalgia2012Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 41, nr 2, s. 95-102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Although self-report based on questionnaire is the common method to obtain information about activities of daily living (ADL) ability in rheumatic diseases, little is known about the relationship between measures of ADL ability based on questionnaire, interview, and observation. The present study examined whether measures of self-reported ADL ability based on questionnaire and interview yielded different results, determined whether the magnitude of the difference varied among women with rheumatoid arthritis (RA), knee osteoarthritis (OA), and fibromyalgia (FM), and investigated the relationships between self-reported and observed ADL ability. Method: The 47 ADL tasks of the ADL taxonomy were used to evaluate self-reported ADL ability based on questionnaire (ADL-Q) and interview (ADL-I), and the Assessment of Motor and Process Skills (AMPS) was used to obtain measures of observed ADL ability. Results: Participants across diagnostic groups reported significantly more ADL ability based on the ADL-Q than on the ADL-I. Moderate correlations were found between the ADL-Q and ADL-I ability measures. Although low to moderate correlations were seen between measures based on the AMPS ADL motor scale and the ADL-Q and ADL-I, respectively, correlations between measures based on AMPS ADL process scale and ADL-Q and ADL-I were generally low. Overall, there was no difference in how the measures based on the two modes of self-report related to the observed ADL ability measures. Conclusion: Measures of self-reported ADL ability based on either questionnaire or interview have limited relationship to each other or to observed performance of ADL tasks.

  • 910.
    Wahlin, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Performance of the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis Is Not Superior to the ACC/AHA Risk Calculator.2018Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752Artikel i tidskrift (Refereegranskat)
  • 911.
    Wahlin, Bengt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Fasth, A. E.
    Karp, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Lejon, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Cd8+cd28- t-lymphocytes are associated with subclinical atherosclerosis in patients with rheumatoid arthritis2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 250-250Artikel i tidskrift (Övrigt vetenskapligt)
  • 912.
    Wahlin, Bengt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Meedt, T.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Jonsson, F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Karp, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Prediction of coronary artery calcification and association with inflammation in rheumatoid arthritis: a follow-up study2014Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, s. 634-635Artikel i tidskrift (Övrigt vetenskapligt)
  • 913.
    Wahlin, Bengt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Meedt, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Jonsson, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Coronary Artery Calcification Is Related to Inflammation in Rheumatoid Arthritis: A Long-Term Follow-Up Study2016Ingår i: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, artikel-id 1261582Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. A long-term follow-up of patients with rheumatoid arthritis (RA) to evaluate factors related to coronary artery calcification (CAC). Methods. All 22 eligible patients (4 males/18 females, mean age 65 years, and RA-duration 30-36 years) from the original (baseline; n = 39) study of atherosclerosis were included. Inflammation, cardiovascular risk factors, and biomarkers were measured at baseline. At follow-up 13 years later, CAC was assessed by computed tomography (CT) and the grade of inflammation was measured. Multivariate analysis of differences between patients with low (0-10) and high CAC (>10) was done by orthogonal projection to latent structures (OPLS). Results. Ten patients had CAC 0-10 and 12 had >10 (range 18-1700). Patients with high CAC had significantly higher ESR (24.3 versus 9.9 mm/h) and swollen joint count (2 versus 0). The OPLS models discriminated between patients having high or low CAC. With only baseline variables, the sensitivity was 73% and the specificity 82%. The model that also included inflammatory variables from follow-up had a sensitivity of 89% and a specificity of 85%. Exclusion of baseline intima media thickness and plaque from the latter model modestly reduced the accuracy (sensitivity 80% and specificity 83%). Conclusions. CAC is related to inflammation in patients with RA.

  • 914.
    Wahren, M.
    et al.
    Karolinska Inst, Stockholm, Sweden..
    Hedlund, M.
    Karolinska Inst, Stockholm, Sweden..
    Thorlacius, G. E.
    Karolinska Inst, Stockholm, Sweden..
    Ivanchenko, M.
    Karolinska Inst, Stockholm, Sweden..
    Kyriakidis, N.
    Karolinska Inst, Stockholm, Sweden..
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala Univ, Uppsala, Sweden..
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Espinosa, A.
    Karolinska Inst, Stockholm, Sweden..
    Sonesson, S. -E
    Type I IFN System Activation In Newborns Exposed To ANTI-RO/SSA Autoantibodies In Utero2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 182-182Artikel i tidskrift (Övrigt vetenskapligt)
  • 915.
    Waldheim, E.
    et al.
    Unit of Rheumatology, Karolinska University Hospital, Huddinge,Stockholm, Sweden & Division of Nursing, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Sweden.
    Elkan, A.-C.
    Unit of Rheumatology, Karolinska University Hospital, Huddinge, Stockholm, Sweden & Department of Medicine, Karolinska Institutet, Huddinge, Sweden & Institute of Environmental Medicine, Karolinska Institutet, Sweden.
    Bergman, Stefan
    Research and Development Centre, Spenshult Hospital, Sweden & Department of Rheumatology, Clinical Sciences, Lund University, Sweden.
    Frostegård, J.
    Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, Sweden.
    Van Vollenhoven, R.
    Unit of Rheumatology, Karolinska University Hospital, Huddinge, Stockholm, Sweden & Department of Medicine, Karolinska Institutet, Solna, Sweden.
    Henriksson, E. W.
    Unit of Rheumatology, Karolinska University Hospital, Huddinge, Stockholm, Sweden & Division of Nursing, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Sweden.
    Extent and characteristics of self-reported pain in patients with systemic lupus erythematosus2013Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 22, nr 2, s. 136-143Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Patients' own experiences of subjective symptoms are scarcely covered, and the objective of this study was to investigate the extent and characteristics of self-reported pain in patients with systemic lupus erythematosus (SLE).

    METHODS: This study comprised a cross-sectional design where 84 patients with SLE were asked to complete self-assessments: visual analogue scale of pain and the Short-Form McGill Pain Questionnaire. Medical assessments, including ESR, SLAM, SLEDAI, and SLICC, were also performed.

    RESULTS: Of the study population, 24% reported higher levels of SLE-related pain (≥40 mm on VAS). This group had a significantly shorter disease duration, higher ESR, and higher disease activity, according to the SLAM and SLEDAI, compared to the rest of the study population. This group mainly used the words "tender," "aching," and "burning" to describe moderate and severe pain, and they used a greater number of words to describe their pain. Of the patients with higher levels of pain, 70% reported their present pain as "distressing." The most common pain location for the whole patient population was the joints. Patients rated their disease activity significantly higher than physicians did.

    CONCLUSION: These findings expand the current knowledge of the extent of SLE-related pain and how patients perceive this pain. The results can contribute to affirmative, supportive and caring communication and especially highlight SLE-related pain in patients with a short disease duration and high disease activity.

  • 916.
    Waldheim, E.
    et al.
    Unit of Rheumatology, Karolinska University Hospital, Sweden & Division of Nursing, Department of Neurobiology, Karolinska Institutet, Sweden.
    Elkan, A.-C.
    Innovation and Development SRQ (Swedish Rheumatology Quality Register), Dept. of Rheumatology, Karolinska University Hospital, Sweden & Institute of Environmental Medicine, Karolinska Institutet, Sweden.
    Pettersson, S.
    Unit of Rheumatology, Karolinska University Hospital, Sweden & Division of Nursing, Department of Neurobiology, Karolinska Institutet, Sweden.
    Van Vollenhoven, R.
    Unit of Rheumatology, Karolinska University Hospital, Sweden & Department of Medicine, Solna, Karolinska Institutet, Sweden.
    Bergman, Stefan
    Research and Development Centre, Spenshult Hospital, Sweden & Department of Rheumatology, Clinical Sciences, Lund University, Sweden.
    Frostegård, J.
    Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, Sweden.
    Welin Henriksson, E.
    Unit of Rheumatology, Karolinska University Hospital, Sweden & Division of Nursing, Department of Neurobiology, Karolinska Institutet, Sweden.
    Health-related quality of life, fatigue and mood in patients with SLE and high levels of pain compared to controls and patients with low levels of pain2013Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 22, nr 11, s. 1118-1127Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective The objective of this paper is to investigate health-related quality of life (HRQoL), fatigue, anxiety and depression in patients with systemic lupus erythematosus (SLE) and higher levels of pain and to compare them to patients with lower levels of pain and controls.

    Method Patients were dichotomized into two groups based on SLE-related pain score on the visual analog scale (VAS): low-pain group (76%, n=64, VAS 0-39 mm) and high-pain group (24%, n=20, VAS 40-100 mm). Sex- and age-matched controls were randomly selected from the general population. Participants were asked to complete questionnaires regarding self-reported pain, HRQoL, fatigue, anxiety and depression. Medical assessments also were recorded.

    Result Fatigue score in the high-pain group (median, 36.5; interquartile range (IQR), 32.5-39.7) was significantly higher (p<0.001) compared to the low-pain group (median, 23; IQR, 14.6-34.1), as well as scores for anxiety (median, 9; IQR, 6.5-11.5) and depression (median, 7.5; IQR, 5.5-9) (p<0.001). The high-pain group had significantly lower scores compared to the low-pain group in all dimensions in the SF-36 (p ≤ 0.001-0.007). No statistical differences were detected between the low-pain group and controls in any measurement except for the dimensions physical function, general health, vitality and social function in SF-36.

    Conclusion Patients with SLE scoring higher degrees of pain were burdened with more fatigue, anxiety and depression and lower levels of HRQoL compared to patients with lower levels of pain who did not differ significantly from the general population in most dimensions. These results elucidate the importance of identifying patients with higher degrees of pain who are probably in need of more extensive multidimensional interventions to decrease symptom burden.

  • 917.
    Waldheim, Eva
    et al.
    Karolinska Inst, Sweden.
    Ajeganova, Sofia
    Karolinska Inst, Sweden.
    Bergman, Stefan
    Univ Gothenburg, Sweden; Spenshult Res and Dev Ctr, Sweden; Lund Univ, Sweden.
    Frostegard, Johan
    Karolinska Inst, Sweden.
    Welin, Elisabet
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Karolinska Inst, Sweden.
    Variation in pain related to systemic lupus erythematosus (SLE): a 7-year follow-up study2018Ingår i: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 37, nr 7, s. 1825-1834Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have previously shown that most patients with systemic lupus erythematosus (SLE) reported low degree of SLE-related pain. However, 24% of the patients reported high degree of SLE-related pain, more fatigue, anxiety and depression, and worse health-related quality of life (HRQoL). To explore SLE-related pain, the presence of long-standing widespread pain, and patient-reported outcomes (PROs) after 7 years. Sixty-four out of 84 patients participated in a 7-year follow-up of the original survey and completed the same questionnaires answered at inclusion: pain (VAS 100 mm), fatigue (MAF), HRQoL (SF-36), anxiety and depression (HADS), and, if appropriate, a pain-drawing. Differences between inclusion and follow-up (change) were calculated. The patients with a low degree of SLE-related pain at inclusion reported no changes at follow-up in pain and PROs except for worsening in physical function in SF-36, median change (IQR) 0 (- 10 to 5), p = 0.024. Half of the patients with high degree of pain at inclusion reported decreased pain at follow-up, median change (IQR) 45 (35 to 65), p = 0.021; fatigue, 8 (8 to 17), p = 0.018; anxiety, 4 (1 to 4), p = 0.035; and depression, 4 (2 to 5), p = 0.018 and improvements in most dimensions of SF-36. The remaining half of the patients reported no changes regarding pain and PROs except for a worsening in vitality in SF-36, 20 (15 to 35), p = 0.0018. All patients with remaining high level of pain indicated long-standing widespread pain. After 7 years, a subgroup of patients with SLE reported remaining high level of SLE-related pain and a high symptom burden, including long-standing widespread pain. Such patients require more observant attention to receive appropriate treatment.

  • 918.
    Wandell, Per
    et al.
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden..
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden..
    Li, Xinjun
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Gasevic, Danijela
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Coll Med & Vet Med, Edinburgh, Midlothian, Scotland..
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, Huddinge, Sweden.;Karolinska Inst, Dept Internal Med Solna, Stockholm, Sweden..
    Sundquist, Jan
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Sundquist, Kristina
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Gout in immigrant groups: a cohort study in Sweden2017Ingår i: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 36, nr 5, s. 1091-1102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our aim was to study the association between country of birth and incidence of gout in different immigrant groups in Sweden. The study population included the whole population of Sweden. Gout was defined as having at least one registered diagnosis in the National Patient Register. The association between incidence of gout and country of birth was assessed by Cox regression, with hazard ratios (HRs) and 95% confidence intervals (95% CI), using Swedish-born individuals as referents. All models were conducted in both men and women, and the full model was adjusted for age, place of residence in Sweden, educational level, marital status, neighbourhood socio-economic status and co-morbidities. The risk of gout varied by country of origin, with highest estimates, compared to Swedish born, in fully adjusted models among men from Iraq (HR 1.82, 95% CI 1.54-2.16), and Russia (HR 1.69, 95% CI 1.26-2.27), and also high among men from Austria, Poland, Africa and Asian countries outside the Middle East; and among women from Africa (HR 2.23, 95% CI 1.50-3.31), Hungary (HR 1.98, 95% CI 1.45-2.71), Iraq (HR 1.76, 95% CI 1.13-2.74) and Austria (HR 1.70, 95% CI 1.07-2.70), and also high among women from Poland. The risk of gout was lower among men from Greece, Spain, Nordic countries (except Finland) and Latin America and among women from Southern Europe, compared to their Swedish counterparts. The increased risk of gout among several immigrant groups is likely explained by a high cardio-metabolic risk factor pattern needing attention.

  • 919. Wang, C.
    et al.
    Ahlford, A.
    Laxman, N.
    Nordmark, G.
    Eloranta, M-L
    Gunnarsson, I.
    Svenungsson, E.
    Padyukov, L.
    Sturfelt, G.
    Jonsen, A.
    Bengtsson, A. A.
    Truedsson, L.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sjowall, C.
    Sandling, J. K.
    Ronnblom, L.
    Syvanen, A-C
    Contribution of IKBKE and IFIH1 gene variants to SLE susceptibility2013Ingår i: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 14, nr 4, s. 217-222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The type I interferon system genes IKBKE and IFIH1 are associated with the risk of systemic lupus erythematosus (SLE). To identify the sequence variants that are able to account for the disease association, we resequenced the genes IKBKE and IFIH1. Eighty-six single-nucleotide variants (SNVs) with potentially functional effect or differences in allele frequencies between patients and controls determined by sequencing were further genotyped in 1140 SLE patients and 2060 controls. In addition, 108 imputed sequence variants in IKBKE and IFIH1 were included in the association analysis. Ten IKBKE SNVs and three IFIH1 SNVs were associated with SLE. The SNVs rs1539241 and rs12142086 tagged two independent association signals in IKBKE, and the haplotype carrying their risk alleles showed an odds ratio of 1.68 (P-value = 1.0 x 10(-5)). The risk allele of rs12142086 affects the binding of splicing factor 1 in vitro and could thus influence its transcriptional regulatory function. Two independent association signals were also detected in IFIH1, which were tagged by a low-frequency SNV rs78456138 and a missense SNV rs3747517. Their joint effect is protective against SLE (odds ratio = 0.56; P-value = 6.6 x 10(-3)). In conclusion, we have identified new SLE-associated sequence variants in IKBKE and IFIH1, and proposed functional hypotheses for the association signals.

  • 920. Wang, Chuan
    et al.
    Kokkonen, Heidi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sandling, Johanna K
    Johansson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Seddighzadeh, Maria
    Padyukov, Leonid
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Syvänen, Ann-Christine
    Preferential association of interferon regulatory factor 5 gene variants with seronegative rheumatoid arthritis in 2 Swedish case-control studies2011Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 38, nr 10, s. 2130-2132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Two interferon regulatory factor 5 (IRF5) gene variants were examined for association with rheumatoid arthritis (RA).

    Methods: A total of 2300 patients with RA and 1836 controls were recruited from 2 independent RA studies in Sweden. One insertion-deletion polymorphism (CGGGG indel) and one single-nucleotide polymorphism (rs10488631) in the IRF5gene were genotyped and analyzed within RA subgroups stratified by rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA).

    Results: The CGGGG indel was preferentially associated with the RF-negative (OR 1.29, p = 7.9 × 10−5) and ACPA-negative (OR 1.27, p = 7.3 × 10−5) RA subgroups compared to the seropositive counterparts. rs10488631 was exclusively associated within the seronegative RA subgroups (RF-negative: OR 1.24, p = 0.016; ACPA-negative: OR 1.27, p = 4.1 × 10−3).

    Conclusion: Both the CGGGG indel and rs10488631 are relevant for RA susceptibility, especially for seronegative RA.

  • 921. Wang, Ning
    et al.
    Shen, Nan
    Vyse, Timothy J
    Anand, Vidya
    Gunnarson, Iva
    Sturfelt, Gunnar
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Elvin, Kerstin
    Truedsson, Lennart
    Andersson, Bengt A
    Dahle, Charlotte
    Örtqvist, Eva
    Gregersen, Peter K
    Behrens, Timothy W
    Hammarström, Lennart
    Selective IgA deficiency in autoimmune diseases2011Ingår i: Molecular medicine, ISSN 1528-3658, Vol. 17, nr 11-12, s. 1383-Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Selective IgA deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety of concomitant autoimmune diseases. In this review, we present data on the prevalence of IgAD in patients with Graves' disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD), myasthenia gravis (MG) and rheumatoid arthritis (RA) based both on our own, recent, large scale screening results and literature data. Genetic factors are important for the development of both IgAD and various autoimmune disorders, including GD, SLE, T1D, CD, MG and RA, and a strong association with the MHC region has been reported. In addition, non-MHC genes, such as IFIH1 and CLEC16A, are also associated with the development of IgAD and some of the above diseases. This indicates a possible common genetic background. In this review, we present suggestive evidence for a shared genetic predisposition between these disorders.

  • 922.
    Wang, Wei-Zhou
    et al.
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China; Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Guo, Xiong
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Duan, Chen
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Ma, Wei Juan
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Zhang, Y G
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Xu, P
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Gao, Z Q
    Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Wang, Z F
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Yan, H
    National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi'an, China.
    Zhang, Y F
    National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi'an, China.
    Yu, Y X
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Chen, J C
    Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Comparative analysis of gene expression profiles between the normal human cartilage and the one with endemic osteoarthritis.2009Ingår i: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 17, nr 1, s. 83-90, artikel-id 18579416Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate the differences in gene expression profiles of adult articular cartilage with endemic osteoarthritis (OA), Kashin-Beck disease (KBD), and the same regions in the normal joint.

    METHODS: The messenger RNA expression profiles of articular cartilage with KBD diagnosed according to "Diagnosing Criteria of Kashin-Beck Disease in China" were compared with the normal cartilage. Total RNA isolated separately from four pairs of the KBD and normal cartilage samples were evaluated by oligonucleotide microarray analysis. The microarray data were confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) amplification and were compared with previously published experiments.

    RESULTS: About 4100 transcripts, which corresponded to 35% of the expressed transcripts, showed >or=twofold differences in expression between the cartilage tissues in pairs. Approximately 2% of the expressed genes (79, 55 genes expressed in KBD>normal; 24 genes expressed in KBD<normal) were commonly expressed in the four pairs of samples. The expression of some genes related to the metabolism, apoptosis, cell proliferation and matrix degradation activity was significantly different in KBD cartilage than in the normal, similar to the findings for genes that inhibit matrix degradation. Comparisons of qRT-PCR data and the previously reported data with the result of gene chips support the validity of our microarray data.

    CONCLUSION: Differences between KBD cartilage and the normal exhibited a similar pattern among the four pairs examined, indicating the presence of common mechanisms mainly including chondrocyte metabolism and apoptosis that contribute to cartilage destruction in KBD.

  • 923.
    Wang, Weizhuo
    et al.
    Department of Orthopedic Surgery, Second Hospital of Xi’an Jiaotong University, Xi'an, China.
    Guo, Xiong
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Xi'an, China.
    Chen, Junchang
    Department of Orthopedic Surgery, Second Hospital of Xi’an Jiaotong University, Xi'an, China.
    Xu, Peng
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Xi'an, China.
    Lammi, Mikko
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Morphology and phenotype expression of types I, II, III, and X collagen and MMP-13 of chondrocytes cultured from articular cartilage of Kashin-Beck Disease.2008Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, ISSN 0315-162X (Print), 1499-2752 (Online), Vol. 35, nr 4, s. 696-702, artikel-id 18322983Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: We investigated the characteristics of cell morphology and expression of types I, II, III, and X collagen and matrix metalloproteinase-13 (MMP-13) of chondrocytes from articular cartilage of adult patients with Kashin-Beck Disease (KBD) in vitro to understand the pathogenesis in chondrocytes.

    METHODS: Samples of articular cartilage were divided into 2 groups: KBD group (8 samples, 8 cases) and the control (8 samples, 8 cases). KBD patients were diagnosed according to "Pathological Criteria to Diagnose KBD in China." Hyaline cartilage was digested with collagenase into cell suspensions and cultured in monolayers. Chondrocyte ultrastructure was observed by electron microscope at 10th day in vitro. Primary articular chondrocytes were seeded on microscope slides and immunostained on 12th day of cultivation for types I, II, III, and X collagens and MMP-13. Positive findings were counted by light microscopy and confirmed by flow cytometric analyses.

    RESULTS: Considerable amounts of vacuoles and distorted nuclei, as well as thickening and irregular arrangement of collagen fibrils, were seen in the KBD samples by electron microscopy. Types I, III, and X collagen were stained in the KBD, but not in the control cultures. The percentages of positive staining for type II collagen were significantly lower in KBD than those in controls (t col II = -5.54, p < 0.001), and for MMP-13 in the KBD group were significantly higher (t MMP-13 = 3.70, p < 0.01).

    CONCLUSION: Phenotype expressions of types I, II, III, and X collagen and MMP-13 in chondrocytes cultured in vitro were significantly different between the KBD and control cultures, indicating degenerative and hypertrophic changes in chondrocytes of KBD articular cartilage.

  • 924.
    Wang, Yan
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Lloyd, Katy A.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Gunasekera, Sunithi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Eriksson, Camilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Ramsköld, Daniel
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Lundberg, Karin
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Jakobsson, Per-Johan
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Malmström, Vivianne
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Grönwall, Caroline
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Repertoire Studies in Rheumatoid Arthritis Reveal B-Cell Distortions and Baseline Shifts in Unmutated IgG2018Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70Artikel i tidskrift (Övrigt vetenskapligt)
  • 925. Weijers, J.
    et al.
    Dessein, P.
    Galarza-Delgado, D.
    Gonzalez-Gay, M.
    Kuriya, B.
    Myasoedova, E.
    Semb, A.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    van Riel, P.
    Different strategies to implement the eular guideline for cardiovascular risk management in daily practice2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 835-835Artikel i tidskrift (Övrigt vetenskapligt)
  • 926.
    Weiner, Maria
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    Segelmark, Mårten
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA)2016Ingår i: Autoimmunity Reviews, ISSN 1568-9972, E-ISSN 1873-0183, Vol. 15, nr 10, s. 978-982Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Anti-neutrophil cytoplasmic antibodies (ANCA) are a family of autoantibodies that react with proteins predominantly expressed in cytoplasmic granules of polymorphonuclear neutrophil granulocytes (PMNs). ANCA was initially detected using indirect immunofluorescence, allowing for different patterns such as p-ANCA (perinuclear) and c-ANCA (cytoplasmic) to be distinguished. Today it is common to detect the antibodies by immunochemical assays such as ELISA using purified proteins as antigens. The strongest association with ANCA is found in the pauci-immune small vessel vasculitides granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). There is compelling evidence that ANCA contributes to the pathogenesis in these conditions. ANCA also occurs in 30%-40% of patients with eosinophilic granulomatosis with polyangiitis (EGPA) and anti-GBM disease, but is uncommon in other forms of vasculitis. ANCA with different specificities have been described with varying frequencies in diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, inflammatory bowel disease, endocarditis, chronic infections and hematopoietic malignancies. ANCA can also develop as an adverse event during pharmacological treatment. These entities are treated quite differently, with therapies ranging from immunosuppressive agents over antibiotics to simply removing the causative drug. A positive ANCA test thus requires a careful diagnostic work-up. (C) 2016 Elsevier B.V. All tights reserved.

  • 927.
    Weiss, R. J.
    et al.
    Department of Molecular Medicine and Surgery, Section of Orthopaedics and Sports Medicine, Karolinska Institutet, Stockholm, Sweden.
    Broström, E.
    Department of Women and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Stark, A.
    Department of Molecular Medicine and Surgery, Section of Orthopaedics and Sports Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wick, M. C.
    Department of Medicine, Section of Rheumatology, Karolinska Institutet, Stockholm, Sweden.
    Wretenberg, Per
    Department of Molecular Medicine and Surgery, Section of Orthopaedics and Sports Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ankle/hindfoot arthrodesis in rheumatoid arthritis improves kinematics and kinetics of the knee and hip: a prospective gait analysis study2007Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 46, nr 6, s. 1024-1028Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To evaluate the effects of ankle/hindfoot arthrodesis in rheumatoid arthritis (RA) patients on gait pattern of the knee and hip.

    Methods: In this prospective follow-up study, 14 RA patients scheduled for ankle/hindfoot arthrodesis (talo-calcaneal, talo-navicular, calcaneo-cuboid and/or talo-crural joints) and 14 age- and sex-matched healthy controls were included. Three-dimensional gait analyses of joint angles, moments and work were performed at the index operation and after 13 months of follow-up. Each patient underwent clinical assessments of pain while walking, overall evaluation of disease activity, Health Related Quality of Life Questionnaire (EQ-5D), activity limitations, maximum walking distance, difficulty with walking surface and gait abnormality. For comparisons of pre- vs post-operative conditions, Wilcoxon's matched pairs test and Friedman ANOVA by rank test were used.

    Results: At follow-up after ankle/hindfoot fusion surgery, RA patients demonstrated a statistically significant improvement in mean range of joint motions, moments and work in the overlying joints such as the knee and hip. Moreover, there was significantly less pain, disease activity, activity limitation, difficulty with walking surface and gait abnormality. EQ-5D and maximum walking distance were also significantly improved at follow-up.

    Conclusions: Our results demonstrate that ankle/hindfoot arthrodesis in RA is an effective intervention to reduce pain and to improve Health Related Quality of Life and functional ability. Moreover, the overlying leg joints experience an improvement in joint motion, muscle-generated joint moments and work during walking. Three-dimensional gait analysis may assist future investigations of the effects of orthopaedic surgery on functional mobility in RA to prevent irreversible disablement.

  • 928.
    Weiss, R. J.
    et al.
    Department of Orthopaedic Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Stark, A.
    Department of Orthopaedic Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Wick, M. C.
    Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
    Ehlin, A.
    Department of Medicine, Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm, Sweden.
    Palmblad, K.
    Department of Rheumatology, Astrid Lindgren Children’s Hospital, Stockholm, Sweden.
    Wretenberg, Per
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Orthopaedic Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Orthopaedic surgery of the lower limbs in 49,802 rheumatoid arthritis patients: results from the Swedish National Inpatient Registry during 1987 to 20012006Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 65, nr 3, s. 335-341Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To analyse changes in the rates of hospital admission and use of orthopaedic surgery to the lower limbs in Swedish patients with rheumatoid arthritis between 1987 and 2001.

    Methods: Data for all rheumatoid patients admitted to hospital between 1987 and 2001 were abstracted from the Swedish National Hospital Discharge Register (SNHDR). The data in the register are collected prospectively, recording all inpatient admissions throughout Sweden. The SNHDR uses the codes for diagnoses at discharge and surgical procedures according to the Swedish version of the International Classification of Diseases (ICD).

    Results: In all, 49,802 individual patients with rheumatoid arthritis were identified, accounting for 159,888 inpatient visits. Hospital admissions for rheumatoid arthritis decreased by 42% (p<0.001) during the period 1987 to 2001. Twelve per cent of all admissions were for a rheumatoid arthritis related surgical procedure to the lower limbs; those admissions decreased markedly (by 16%) between 1987 and 1996, and by 12% between 1997 and 2001, as did the overall number of rheumatoid arthritis related surgical procedures to the lower limbs during both time periods. Between 1997 and 2001, 47% of all rheumatoid arthritis related surgical procedures were total joint arthroplasties. There was an overall trend towards reduced length of hospital stay after orthopaedic surgery to the lower limbs during the study period.

    Conclusions: Rates of hospital admission and rheumatoid arthritis related surgical procedures to the lower limbs in Swedish patients with rheumatoid arthritis decreased between 1987 and 2001. This may reflect trends in disease severity, management, and health outcomes of this disease in Sweden.

  • 929.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Manivel, Vivek A
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Lysholm, Jörgen
    Clinic of Rheumatology, Falun Hospital, Falun.
    Knight, Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and without autoantibodies2015Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, nr 10, s. 1923-1928Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Cathepsin S and cathepsin L are endosomal proteolytic enzymes involved in the degradation of extracellular matrixes, angiogenesis and antigen presentation. Cathepsins could thus play several roles in the disease process of RA. The aim of this study was to examine differences in cathepsin S and cathepsin L levels in serum and SF of RA patients with and without ACPA and RF.

    METHODS: In this study 121 patients with RA and clinical signs of knee synovitis were recruited. Patient characteristics were collected and matched samples of serum and SF were analysed for cathepsin S, cathepsin L, ACPA, IgA and IgM RF, CRP and MMP3.

    RESULTS: SF levels of cathepsin L, cathepsin S and MMP3 were significantly higher than in serum. Serum levels of both cathepsins were significantly higher in patients with ACPA, IgM-RF and IgA-RF compared with patients without these antibodies. SF levels of both cathepsins correlated with DAS28 and CRP in ACPA- and RF-positive but not in seronegative patients.

    CONCLUSION: The differences in cathepsin S and cathepsin L between RA patients with and without autoantibodies indicate that these cathepsins have a specific role in the disease process of seropositive RA. In this phenotype, cathepsin serum levels may reflect the autoimmune activity, whereas the levels in SF may reflect the local inflammatory and matrix degrading process in the joint.

  • 930.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Manivel, Vivek
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Lysholm, J.
    Knight, A.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and without autoantibodies2014Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr S127, s. 53-53Artikel i tidskrift (Övrigt vetenskapligt)
  • 931.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Saxne, T
    Lund University, Department of Clinical Sciences, Section of Rheumatology.
    Manivel, Vivek Anand
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Lysholm, J
    Falun Hospital, Clinic of Rheumatology.
    Knight, Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Pentraxin 3 in serum and synovial fluid of patients with rheumatoid arthritis with and without autoantibodies2017Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 46, nr 5, s. 346-352Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES:

    Pentraxin 3 (PTX3) is a locally produced multifunctional protein involved in inflammation, matrix deposition, and immunity. As patients with seropositive rheumatoid arthritis (RA) have a more severe disease course and higher risk of joint destruction than seronegative patients, the aim of the present study was to examine differences in PTX3 in synovial fluid (SF) (and serum) in seropositive compared to seronegative RA, and other local markers of inflammation and destruction.

    METHOD:

    Ninety-seven RA patients with knee effusion were included. Serum and SF levels of PTX3, as well as serum levels of anti-citrullinated protein antibody and rheumatoid factor of immunoglobulin A and M subclasses, and markers of inflammation and potential destruction in SF: white blood cell counts, tumour necrosis factor, interleukin-6, vascular endothelial growth factor, metalloproteinase 3, and cartilage oligomeric matrix protein, were analysed. In addition, a radiographic knee examination was performed.

    RESULTS:

    Seropositive patients had significantly higher PTX3 levels in SF than seronegative patients, whereas there was no difference for serum levels. SF-PTX3 levels correlated with disease activity and with local inflammatory markers, especially polymorphonuclear cells, and with autoantibody levels. There was no correlation between PTX3 levels in serum and SF.

    CONCLUSION:

    The correlation of disease activity and autoantibody levels with SF-PTX3 levels in antibody-positive patients suggests a role for PTX3 in the inflammatory process specifically in seropositive RA joints, and supports the hypothesis that seropositive and seronegative RA are different disease entities. Polymorphonuclear granulocytes may be an important source of PTX3 in RA SF.

  • 932.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Oberg, K.
    Falun Cent Hosp, Rheumatol Clin, Falun, Sweden.
    The dosing of intra-articular triamcinolone hexacetonide for knee synovitis in chronic polyarthritis: a randomized controlled study2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 987-987Artikel i tidskrift (Övrigt vetenskapligt)
  • 933.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Knight, Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Lysholm, Jörgen
    Saxne, Tore
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Outcome predictors of intra-articular glucocorticoid treatment for knee synovitis in patients with rheumatoid arthritis: a prospective cohort study2014Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 16, nr 3, s. R129-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION:

    Intra-articular glucocorticoid treatment (IAGC) is widely used for symptom relief in arthritis. However, knowledge of factors predicting treatment outcome is limited. The aim of the present study was to identify response predictors of IAGC for knee synovitis in patients with rheumatoid arthritis (RA).

    METHODS:

    In this study 121 RA patients with synovitis of the knee were treated with intra-articular injections of 20 mg triamcinolone hexacetonide. They were followed for 6 months and the rate of clinical relapse was studied. Non-responders (relapse within 6 months) and responders were compared regarding patient characteristics and knee joint damage as determined by the Larsen-Dale index. In addition, matched samples of serum and synovial fluid were analyzed for factors reflecting the inflammatory process (C-reactive protein, interleukin 6, tumour necrosis factor alpha, vascular endothelial growth factor), joint tissue turnover (cartilage oligomeric matrix protein, metalloproteinase 3), and autoimmunity (antinuclear antibodies, antibodies against citrullinated peptides, rheumatoid factor).

    RESULTS:

    During the observation period, 48 knees relapsed (40%). Non-responders had more radiographic joint damage than responders (p = 0.002) and the pre-treatment vascular endothelial growth factor (VEGF) level in synovial fluid was significantly higher in non-responders (p = 0.002).

    CONCLUSIONS:

    Joint destruction is associated with poor outcome of IAGC for knee synovitis in RA. In addition, higher levels of VEGF in synovial fluid are found in non-responders, suggesting that locally produced VEGF is a biomarker for recurrence of synovial hyperplasia and the risk for arthritis relapse.

  • 934.
    Weitoft, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Öberg, Kjell
    Division of Internal Medicine, Gävle Hospital, Sweden.
    Does modern treatment of early rheumatoid arthritis reduce the need for intra-articular glucocorticoids?2013Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 42, nr 2, s. 163-164Artikel i tidskrift (Refereegranskat)
  • 935.
    West, Christina E.
    et al.
    World University of Network, Sweden; Umeå University, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. World University of Network, Sweden.
    Kozyrskyj, Anita L.
    World University of Network, Sweden; University of Alberta, Canada.
    Prescott, Susan L.
    World University of Network, Sweden; University of Western Australia, Australia.
    Probiotics for treatment and primary prevention of allergic diseases and asthma: looking back and moving forward2016Ingår i: EXPERT REVIEW OF CLINICAL IMMUNOLOGY, ISSN 1744-666X, Vol. 12, nr 6, s. 625-639Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Microbial ecosystems cover the surface of the human body and it is becoming increasingly clear that our modern environment has profound effects on microbial composition and diversity. A dysbiotic gut microbiota has been associated with allergic diseases and asthma in cross-sectional and observational studies. In an attempt to restore this dysbiosis, probiotics have been evaluated in randomized controlled trials. Here, we review treatment and primary prevention studies, recent meta-analyses, and discuss the current understanding of the role of probiotics in this context. Many meta-analyses have shown a moderate benefit of probiotics for eczema prevention, whereas there is less evidence of a benefit for other allergic manifestations. Because of very low quality evidence and heterogeneity between studies, specific advice on the most effective regimens cannot yet be given -not even for eczema prevention. To be able to adopt results into specific recommendations, international expert organizations stress the need for well-designed studies.

  • 936. Westerlind, H.
    et al.
    Holmqvist, M.
    Ljung, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm.
    Frisell, T.
    Askling, J.
    Siblings of patients with rheumatoid arthritis are at increased risk of acute coronary syndrome2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 119-119Artikel i tidskrift (Övrigt vetenskapligt)
  • 937.
    Westermark, T
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Isaksson, T
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Holmberg, P
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kjörell, U
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Increase in bombesin-like peptides in the spinal cord after dexamethasone treatment of adrenalectomized rats1999Ingår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 275, nr 3, s. 179-182Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The potential influence of corticosteroids on the bombesin (BN)-like peptide family is unknown. Therefore, the effects of adrenalectomy (ADX) on the nervous system of Sprague-Dawley rats, some of them being treated with high doses of the synthetic glucocorticoid dexamethasone (DEX), were investigated. After 8-10 days of treatment, the rats were sacrificed and tissues were prepared for radioimmunoassay (RIA) and immunohistochemical examination. We found an increase in BN-like immunoreactivity in the superficial layers of the dorsal horn of the lumbar spinal cord in the ADX + DEX animals. This increase was confirmed by RIA (P < 0.05). The observations show that the expression of BN-like peptides is influenced by glucocorticoids. The altered levels of BN-like peptides may be related to the trophic and antinociceptive effects previously reported for these peptides. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

  • 938.
    Westermark, T
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Kjörell, U
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Increased content of bombesin/GRP in human synovial fluid in early arthritis: different pattern compared with substance P2001Ingår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 19, nr 6, s. 715-720Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective Bombesin (BN) and the mammalian homologue gastrin-releasing peptide (GRP) are known trophic factors, neurotransmitters and paracrine hormones. BN/GRP has not previously been demonstrated in synovial fluid. In this study, the amounts of BN/GRP and substance P (SP) present in synovial fluid from the knee joints of patients with rheumatoid arthritis (RA) and of healthy, controls were measured.

    Methods Synovial fluid from the knee joint was collected from patients with either longstanding RA (n = 32) or early arthritis (symptoms for < 12 months; n = 9) and from control subjects, i.e., individuals without known joint disease (n = 10). These samples were analyzed using radioimmunoassays.

    Results Levels of BN/GRP-like peptide were below the assay detection limits in synovial fluid from controls. Detectable levels of immunoreactive BN/GRP were present in the majority of patients with either longstanding RA or early arthritis. The levels were significantly higher in the synovial fluid from patients classified as having early, arthritis compared with those with longstanding RA (p < 0.05). There was a strong correlation between BN/GRP levels and the number of leukocytes in the synovial fluid in the patients with early arthritis. The levels of SP-like peptide in the patients, whether with early arthritis or longstanding RA, were significantly elevated compared with controls. However there was no difference in the levels between these two patient groups.

    Conclusions These observations show that BN/GRP-like peptide is present in the synovial fluid of joints affected by arthritis and that the pattern of BN/GRP increase differs from that of SP It appears as if the presence of BN/GRP is particularly related to the early processes of joint involvement. These observations are of interest because BN/GRP has well-known trophic and paracrine effects and chondrocytes have recently been shown to produce neuropeptides such as BN/GRP.

  • 939. Westra, Harm-Jan
    et al.
    Martinez-Bonet, Marta
    Onengut, Suna
    Lee, Annette
    Luo, Yang
    Teslovich, Nikola
    Worthington, Jane
    Martin, Javier
    Huizinga, T. W. J.
    Klareskog, Lars
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Chen, Wei-Min
    Quinlan, Aaron
    Todd, John
    Eyre, Stephen
    Nigrovic, Peter
    Gregersen, Peter
    Rich, Stephen
    Raychaudhuri, Soumya
    Fine-Mapping Identifies Causal Variants for RA and T1D in DNASE1L3, Sirpg, MEG3, TNFAIP3 and CD28/CTLA4 Loc2017Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69Artikel i tidskrift (Övrigt vetenskapligt)
  • 940.
    Wiberg, Kristina
    et al.
    Umeå universitet, Medicinska fakulteten.
    Öhman, Marie-Louise
    Umeå universitet, Medicinska fakulteten.
    Bergström, Ulrika
    Umeå universitet, Medicinska fakulteten.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Increased Incidence Of Low-Energy Fractures In Rheumatoid Arthritis Patients2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Special Issue, Supplement 10, s. S166-S166, Meeting Abstract: 383Artikel i tidskrift (Övrigt vetenskapligt)
  • 941. Wibetoe, G.
    et al.
    Sexton, J.
    Ikdahl, E.
    Rollefstad, S.
    Kitas, G.
    van Riel, P.
    Gabriel, S.
    Kvien, T. K.
    Douglas, K.
    Sandoo, A.
    Arts, E. E.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Karpouzas, G.
    Dessein, P. H.
    Tsang, L.
    EI-Gabalawy, H.
    Hitchon, C. A.
    Pascual-Ramos, V.
    Contreas-Yanes, I.
    Sfikakis, P. P.
    Gonzalez-Gay, M. A.
    Colunga-Pedraz, I. J.
    Galarza-Delgado, D. A.
    Azpiri-Lopez, J. R.
    Crowson, C. S.
    Semb, A. G.
    Cardiovascular risk age and vascular age estimations in predicting cardiovascular events in rheumatoid arthritis patients2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 1743-1743Artikel i tidskrift (Övrigt vetenskapligt)
  • 942. Wibetoe, Grunde
    et al.
    Crowson, Cynthia S.
    Sexton, Joseph
    Rollefstad, Silvia
    Ikdahl, Eirik
    Kitas, George D.
    van Riel, Piet
    Gabriel, Sherine E.
    Kvien, Tore K.
    Douglas, Karen
    Sandoo, Aamer
    Arts, Elke
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Karpouzas, George
    Dessein, Patrick H.
    Tsang, Linda
    El-Gabalawy, Hani
    Hitchon, Carol A.
    Pascual-Ramos, Virginia
    Contreras-Yanez, Irazu
    Sfikakis, Petros P.
    Zampeli, Evangelia
    Angel Gonzalez-Gay, Miguel
    Corrales, Alfonso
    Colunga-Pedraza, Iris J.
    Galarza-Delgado, Dionicio A.
    Ramon Azpiri-Lopez, Jose
    Semb, Anne Grete
    Performance of Cardiovascular Risk Age and Vascular Age Estimations in Predicting Cardiovascular Events in Rheumatoid Arthritis2017Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background/Purpose: Rheumatoid arthritis (RA) patients are at high risk of cardiovascular disease (CVD). Risk algorithms for the general population lack precision when applied to RA patients and validated RA-specific CVD prediction models are missing. Risk age estimations are recommended as adjuncts to assessment of absolute 10-year risk of fatal CVD events. Two risk age models based on the Systematic Coronary Risk Evaluation (SCORE) algorithm have been developed; the cardiovascular risk age and the vascular age. However, the performance of these models has not been compared. Using longitudinal data on CVD events in RA patients, we aimed to compare the discriminative ability of cardiovascular risk age and vascular age among RA patients and in subgroups of RA patients based on disease characteristics. Methods: Patients with RA were included from an international consortium, aged 30-70 years at baseline. Those with prior CVD, diabetes and/or users of lipid-lowering and/or antihypertensive therapy at baseline were excluded. Cardiovascular risk age was estimated based on chronologic age, smoking status, total cholesterol and systolic blood pressure at baseline. Vascular age was derived from the 10-year risk of CVD according to the SCORE algorithm, with or without high density lipoprotein cholesterol, using the equations for low and high risk countries. Performance of each risk age model in predicting CVD events was assessed using the concordance index. Results: Among the1867 RA patients included, 74% were female, median (inter-quartile range) age and disease duration were 52.0 (44.0, 59.9) and 0.6 (0.1, 6.4) years, 72.5% were rheumatoid factor positive, 24.7% were using glucocorticoids and 10.3% were using biologics at baseline. Overall, 144 CVD events occurred and median follow-up time was 5.0 (2.6, 9.3) years. Median difference between estimated risk age and chronologic age was 4.0 to 6.7 years, depending on the specific risk age model applied. Overall, the C-index across risk models ranged from 0.71 to 0.73 with standard errors of 0.03. Across prediction models, the lowest observed concordance was found among women and in glucocorticoid users and in those with new-onset disease (≤1 year). Additional analyses including RA patients on cardio preventive therapy yielded slightly lower c-indexes. Since SCORE was developed for use in Europe, we performed analyses on European RA patients, which yielded similar results. The trend of reduced concordance among women, glucocorticoid users and RA patients with short disease duration was preserved in these additional analyses. Conclusion: The cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. Sex, disease duration and/or glucocorticoid treatment may influence the performance of risk age estimations.

  • 943.
    Wigerblad, Gustaf
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Lloyd, Katy A.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Sahlström, Peter
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Chemin, Karine
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Steen, Johanna
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Titcombe, Philip J.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden;Univ Minnesota, Sch Med, Dept Med, Ctr Immunol, Minneapolis, MN 55455 USA.
    Zhou, Diana
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Stalesen, Ragnhild
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Marklein, Bianka
    Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany.
    Ossipova, Elena
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Piccoli, Luca
    Univ Svizzera Italiana, Inst Res Biomed, Bellinzona, Switzerland.
    Lanzavecchia, Antonio
    Univ Svizzera Italiana, Inst Res Biomed, Bellinzona, Switzerland.
    Mueller, Daniel L.
    Univ Minnesota, Sch Med, Dept Med, Ctr Immunol, Minneapolis, MN 55455 USA.
    Skriner, Karl
    Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany.
    Klareskog, Lars
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Wermeling, Fredrik
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Malmström, Vivianne
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    Grönwall, Caroline
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
    PAD4-Independent Interaction of ACPA with Nuclear Antigens in Apoptotic Cells and Neutrophil Extracellular Traps (NETs) Defines a Subset of Autoantibodies2018Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70Artikel i tidskrift (Övrigt vetenskapligt)
  • 944.
    Wikander, Robert
    et al.
    Högskolan i Halmstad, Sektionen för ekonomi och teknik (SET), Bio- och miljösystemforskning (BLESS), Biomekanik och biomedicin.
    Augustsson, Johan
    Högskolan i Halmstad, Sektionen för ekonomi och teknik (SET), Bio- och miljösystemforskning (BLESS), Biomekanik och biomedicin.
    Kan ett nyutvecklat handledsstöd förbättra möjligheterna för funktionell träning av övre extremiteten för reumatiker?: En SEMG-studie2011Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    I en generell rehabiliteringsfas så är styrketräning en viktig del på grund av att muskelsvaghet kan bidra till nedsatt funktion och det leder till avvikande rörelsemönster. Begränsad range of motion (ROM) i övre extremiteten är en bidragande faktor till att individer inte kan utföra vardagliga aktiviteter. Flera studier har dokumenterat att patienter med reumatoid artrit (RA) har försämrad handfunktion på grund av nedsatt greppstyrka och inskränkningar i ROM.

    Funktionell träning är till för att stärka upp de svaga musklerna som orsakar obalansen eller smärtan samtidigt som kroppen blir rörligare. Genom att använda sig av vardagliga rörelser och implementera dem med träningen så görs träningen mer funktionell. Syftet med studien var att utveckla och utvärdera ett nytt handledsstöd för att öka möjligheterna till funktionell träning av övre extremiteterna för reumatiker.

    I studien deltog 27 kvinnor varav 8 stycken med diagnosen RA och 19 stycken friska. Medelåldern var 38år (20-73år). Muskelaktiviteten i m. trapezius och m. rhomboideus mättes med hjälp av ytelektromyografi (sEMG) under tre övningar för att jämföra skillnaderna mellan både RA och friska, samt med och utan framtagen produkt.

    Resultaten visade att det går att träna övre extremiteten utan behöva använda handens greppstyrka. Det var ingen signifikant skillnad i muskelaktivitet i m. trapezius och m. rhomboideus med eller utan produkt. Resultaten visade även att reumatisk muskulatur inte skiljer sig från frisk. Deltagarnas subjektiva uppfattning var mycket positiv där 24 av 27 deltagare upplevde det som enklare att genomföra övningen med produkten och 9 av 27 upplevde det enklare att fokusera på övningen.

    Studien har resulterat i ett nytt handledsstöd som möjliggör funktionell träning av m.trapezius och m.rhomboideus för reumatiker.

  • 945.
    Wikström, I.
    et al.
    Malmö University Hospital, Sweden.
    Arvidsson, Barbro
    Högskolan i Halmstad, Sektionen för hälsa och samhälle (HOS), Centrum för forskning om välfärd, hälsa och idrott (CVHI).
    Nilsson, K.
    Malmö University Hospital, Sweden.
    Roos, E.
    Lund University, Sweden.
    Jacobsson, L. T. H.
    Lund University, Sweden.
    Validity and reliability of anew leisure index - The PSLS2007Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 66, nr Suppl. 2, s. 661-661Artikel i tidskrift (Övrigt vetenskapligt)
  • 946. Wingstrand, Maria
    et al.
    Hagglund, Gunnar
    Rodby-Bousquet, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Ankle-foot orthoses in children with cerebral palsy: a cross sectional population based study of 2200 children2014Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 15, s. 327-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Ankle-foot orthosis (AFO) is the most frequently used type of orthosis in children with cerebral palsy (CP). AFOs are designed either to improve function or to prevent or treat muscle contractures. The purpose of the present study was to analyse the use of, the indications for, and the outcome of using AFO, relative to age and gross motor function in a total population of children with cerebral palsy. Methods: A cross-sectional study was performed of 2200 children (58% boys, 42% girls), 0-19 years old (median age 7 years), based on data from the national Swedish follow-up programme and registry for CP. To analyse the outcome of passive ankle dorsiflexion, data was compared between 2011 and 2012. The Gross motor classification system (GMFCS) levels of included children was as follows: I (n = 879), II (n = 357), III (n = 230), IV (n = 374) and V (n = 355). Results: AFOs were used by 1127 (51%) of the children. In 215 children (10%), the indication was to improve function, in 251 (11%) to maintain or increase range of motion, and 661 of the children (30%) used AFOs for both purposes. The use of AFOs was highest in 5-year-olds (67%) and was more frequent at lower levels of motor function with 70% at GMFCS IV-V. Physiotherapists reported achievement of functional goals in 73% of the children using AFOs and maintenance or improvement in range of ankle dorsiflexion in 70%. Conclusions: AFOs were used by half of the children with CP in Sweden. The treatment goals were attained in almost three quarters of the children, equally at all GMFCS levels. AFOs to improve range of motion were more effective in children with a more significant decrease in dorsiflexion at baseline.

  • 947.
    Wirestam, Lina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Biomarkers of disease activity and organ damage in systemic lupus erythematosus2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a systemic inflammatory disease. Clinically, the distinction between ongoing inflammation attributed to SLE, and organ damage due to medication or co-morbidities remains challenging. In addition, SLE is a heterogeneous disease where the various disease phenotypes complicate the search for biomarkers that adequately reflect disease activity and/or signs of increasing organ damage. The aim of the thesis was to investigate and evaluate potential new biomarkers of disease activity and/or organ damage in SLE patients.

    High mobility group box protein-1 (HMGB1) is a nuclear non-histone protein that can shuttle to the cytoplasm, become secreted extracellularly, and participate in systemic inflammation. Administration of monoclonal anti-HMGB1 antibodies has been reported both to attenuate and intensify disease in animal models of arthritis and lupus. In Paper I of the thesis, circulating anti-HMGB1 was found in 23% of the SLE patients and correlated with disease activity variables. The biological role of these autoantibodies remains to be elucidated.

    As a consequence of massive circulating levels of cellular debris and immune complexes, SLE patients have insufficient capacity to remove such material via the reticuloendothelial system. Pentraxin 3 (PTX3) may possibly protect against lupus flares due to classical complement activation, opsonization of apoptotic cells, and cytokine induction. In Paper II, circulating PTX3 was found to be inhibited or exhausted by interferon (IFN)-α, a key cytokine of SLE pathogenesis, and serum levels of PTX3 in SLE patients were inversely related to IFN-α levels. Suppressed PTX3 levels may contribute to a vicious circle resulting in impaired waste clearance, autoantigen exposure and autoantibody production, and sustained disease activity.

    Osteopontin (OPN), a protein known to influence cell signaling and apoptosis, has been proposed as a marker of organ damage in pediatric lupus. In a Swedish cross-sectional study, circulating OPN levels were found to be raised in SLE (Paper III). In patients with recent-onset disease, OPN reflected disease activity, while in established disease, OPN appeared to mirror damage accrual and cardiovascular damage. In Paper IV, OPN was instead analyzed in an international longitudinal multi-center study based on patients with recent-onset SLE and follow-up data. OPN turned out to be a poor predictor of organ damage, but significant associations were observed between OPN and disease activity both at disease onset, as well as over 5 years of follow-up.

    In conclusion, increased anti-HMGB1 antibody and decreased PTX3 levels could potentially sustain the impaired waste-disposal. Of the molecules analyzed in this thesis, OPN seems to be the best marker of disease activity. Further studies of these proteins may help to better understand SLE pathogenesis and to optimize treatment of patients.

  • 948.
    Wirestam, Lina
    et al.
    Linköpings universitet.
    Enocsson, Helena
    Linköpings universitet.
    Skogh, Thomas
    Linköpings universitet.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sjöwall, Christopher
    Linköpings universitet.
    Wetterö, Jonas
    Linköpings universitet.
    Interferon-α coincides with suppressed levels of pentraxin-3 (PTX3) in systemic lupus erythematosus and regulates leucocyte PTX3 in vitro2017Ingår i: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 189, nr 1, s. 83-91Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dysfunctional elimination of cell debris, and the role of opsonins such as pentraxins, is of interest regarding systemic lupus erythematosus (SLE) pathogenesis. Interferon (IFN)- is typically elevated during SLE flares, and inhibits hepatocyte production of the pentraxin C-reactive protein' (CRP), partly explaining the poor correlation between CRP levels and SLE disease activity. The extrahepatically produced pentraxin 3' (PTX3) shares waste disposal functions with CRP, but has not been studied extensively in SLE. We analysed serum PTX3 in SLE, and assessed its interference with IFN- in vitro. Serum samples from 243 patients with SLE and 100 blood donors were analysed regarding PTX3. Patient sera were analysed for IFN-, and genotyped for three PTX3 single nucleotide polymorphisms reported previously to associate with PTX3 levels. Stimulated PTX3 release was assessed in the presence or absence of IFN- in blood donor neutrophils and peripheral blood mononuclear cells (PBMC). Serum PTX3 was 44% lower in patients with SLE compared to blood donors (P<00001) and correlated with leucocyte variables. Patients with undetectable IFN- had 29% higher median PTX3 level than patients with detectable IFN- (P=001). PTX3 production by PBMC was inhibited by IFN-, whereas neutrophil degranulation of PTX3 was increased. No differences in PTX3 levels were observed between the SNPs. In conclusion, median serum PTX3 is lower in SLE (especially when IFN- is detectable) compared to blood donors. In addition to its potential consumption during waste disposal, it is plausible that IFN- also attenuates PTX3 by inhibiting synthesis by PBMC and/or exhausting PTX3 storage in neutrophil granules.

  • 949.
    Wirestam, Lina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Frodlund, Martina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Enocsson, Helena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Wetterö, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE2017Ingår i: Lupus Science and Medicine, ISSN 2053-8790, E-ISSN 1625-9823, Vol. 4, nr 1, s. 7artikel-id 000225Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective The variety of disease phenotypes among patients with SLE challenges the identification of new biomarkers reflecting disease activity and/or organ damage. Osteopontin (OPN) is an extracellular matrix protein with immunomodulating properties. Although raised levels have been reported, the pathogenic implications and clinical utility of OPN as a biomarker in SLE are far from clear. Thus, the aim of this study was to characterise OPN in SLE.

    Methods Sera from 240 well-characterised adult SLE cases classified according to the American College of Rheumatology (ACR) and/or the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and 240 population-based controls were immunoassayed for OPN. The SLE Disease Activity Index 2000 (SLEDAI-2K) was used to evaluate disease activity and the SLICC/ACR Damage Index (SDI) to detect damage accrual.

    Results Serum OPN levels were in average raised fourfold in SLE cases compared with the controls (p<0.0001). OPN correlated with SLEDAI-2K, especially in patients with a disease duration of <12 months (r=0.666, p=0.028). OPN was highly associated with SDI (p<0.0001), especially in the renal (p<0.0001), cardiovascular (p<0.0001) and malignancy (p=0.012) domains. Finally, OPN associated with coherent antiphospholipid syndrome (APS; p=0.009), and both clinical and laboratory criteria of APS had significant positive impact on OPN levels.

    Conclusions In this cross-sectional study, circulating OPN correlates with disease activity in recent-onset SLE, reflects global organ damage and associates with APS. Longitudinal studies to dissect whether serum OPN also precedes and predicts future organ damage are most warranted.

  • 950.
    Wixner, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pilebro, Bjorn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundgren, Hans-Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Olsson, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Effect of doxycycline and ursodeoxycholic acid on transthyretin amyloidosis2017Ingår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, nr 1, s. 78-79Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Doxycycline has been shown to disrupt transthyretin amyloid (ATTR) fibrils [1] and tauro-ursodeoxycholic acid (TUDCA) has been shown to reduce TTR toxic aggregates in mice [2]. Further, in 2010 Cardoso et al. showed that a combined doxycycline/TUDCA treatment had a synergistic effect, decreasing ATTR deposition. Ursodeoxycholic acid (UDCA) is a bile acid used for the treatment of certain cholestatic syndromes with an efficacy similar to that of TUDCA. Based on this knowledge, we wanted to explore if treatment with doxycycline and UDCA (Dox/Urso) would prevent disease progression in ATTR amyloidosis. UDCA was selected since TUDCA is not available in Sweden.

1617181920 901 - 950 av 987
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