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- Andréasson, Kristofer, et al.
(författare)
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Disease Features and Gastrointestinal Microbial Composition in Patients with Systemic Sclerosis from Two Independent Cohorts
- 2022
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Ingår i: ACR Open Rheumatology. - : Wiley. - 2578-5745. ; 4:5, s. 417-425
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The study objective was to examine alterations in gastrointestinal (GI) microbial composition in patients with systemic sclerosis (SSc) and to investigate the relationship between SSc features and GI microbiota using two independent, international cohorts. Methods: Prospective patients with SSc from Lund University (LU), Sweden, from the University of California, Los Angeles (UCLA), United States, and control subjects provided stool specimens for 16S ribosomal RNA sequencing. Alpha and beta diversity analyses were performed. Multivariate negative binomial models identified differentially abundant genera between groups. Results: Patients from LU with SSc (n = 106) with recent SSc diagnosis (median disease duration 2.0 years) had lower abundance of commensal genera (eg, Faecalibacterium) and higher abundance of pathobiont genera (eg, Desulfovibrio) than LU-controls (n = 85). Patients from UCLA with SSc (n = 71) had a similar prevalence of females, a similar body mass index, and similar age but an increased disease duration (median 7.1 years) compared with patients from LU with SSc. Factors associated with beta diversity in patients with SSc from both LU and UCLA included disease duration (P = 0.0016), interstitial lung disease (P = 0.003), small intestinal bacterial overgrowth (P = 0.002), and immunosuppression use (P = 0.014). In multivariable analysis, the UCLA-SSc cohort had higher abundance of specific pathobiont genera (eg, Streptococcus) compared with the LU-SSc cohort. Conclusion: Enrichments and depletions in certain microbial genera were observed in patients recently diagnosed with SSc, suggesting that dysbiosis is present in early SSc. Specific disease features were independently associated with fecal microbial composition in both cohorts. After controlling for these factors, the abundance of several pathobiont bacteria differed between the cohorts, suggesting that environmental factors, along with disease manifestations, should be considered in future SSc studies.
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- Andréasson, Kristofer, et al.
(författare)
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Treatment for Rheumatoid Arthritis Associated With Alterations in the Gastrointestinal Microbiota
- 2024
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Ingår i: ACR Open Rheumatology. - 2578-5745.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Emerging research suggests that rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This prospective pilot study evaluates changes in intestinal microbial composition in patients with RA initiating treatment with either methotrexate (MTX) or a tumor necrosis factor inhibitor (TNFi). Methods: Consecutive patients, fulfilling the 2010 American College of Rheumatology/EULAR classification criteria for RA, who started treatment with either MTX or TNFi delivered a stool sample upon initiation of immunosuppression and 3 months later. A 16S ribosomal RNA gene-based validated microbiota test (GA-map Dysbiosis Index Score [DIS], Genetic Analysis, Oslo, Norway) was used to evaluate for the presence and degree of dysbiosis. Fecal levels of Prevotella copri (P. copri) were analyzed by custom-made quantitative polymerase chain reaction. Changes in microbial composition were analyzed in relation to changes in disease activity, as measured by the disease activity score based on 28-joint counts, using C-reactive protein. Results: At baseline, dysbiosis was present in 33 of 50 (66%) participants and more common in participants with more than 2 years of disease duration (P = 0.019). At the 3-month follow-up, 27 of 50 (54%) were good treatment responders and the DIS had improved in 14 of 50 (28%). Participants initiating TNFi more often exhibited improvement in the DIS compared with those initiating MTX (P = 0.031). P. copri was identified in 32 of 50 (64%) at baseline. An improvement in disease activity score based on 28-joint counts, using C-reactive protein was associated with a simultaneous decrease in P. copri abundance (rs = 0.30, P = 0.036). Conclusion: This study affirms that dysbiosis is a feature of RA. Although patients were not randomized to MTX or TNFi, the findings suggest that specific therapies may differentially modulate the gastrointestinal microbiota in RA. The association between P. copri and treatment response requires further study.
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- Hamberg, Viggo, et al.
(författare)
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Anti-Ro52 positivity is associated with progressive interstitial lung disease in systemic sclerosis-an exploratory study
- 2023
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Ingår i: Arthritis Research & Therapy. - : BioMed Central (BMC). - 1478-6354 .- 1478-6362. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc). Prognostic biomarkers are needed to identify SSc-ILD patients at risk for progressive pulmonary fibrosis. This study investigates autoantibodies measured in bronchoalveolar lavage (BAL) fluid and in serum in reference to the clinical disease course of SSc-ILD.Methods: Fifteen patients with new onset SSc-ILD underwent bronchoscopy. Autoantibody levels were analyzed using addressable laser bead immunoassay from BAL fluid and the serum. In a separate longitudinal cohort of 43 patients with early SSc-ILD, autoantibodies in serum were measured at baseline and pulmonary function tests were performed at least 2 times over the course of at least 2 or more years. Linear mixed effect models were created to investigate the relationship between specific autoantibodies and progression of SSc-ILD. Finally, lung tissue from healthy controls and from subjects with SSc was analyzed for the presence of the Ro52 antigen using immunohistochemistry.Results: Among SSc-ILD patients who were positive for anti-Ro52 (N = 5), 3 (60%) had enrichment of anti-Ro52 in BAL fluid at a ratio exceeding 50x. In the longitudinal cohort, 10/43 patients (23%) were anti-Ro52 positive and 16/43 (37%) were anti-scl-70 positive. Presence of anti-Scl-70 was associated with a lower vital capacity (VC) at baseline (-12.6% predicted VC [%pVC]; 95%CI: -25.0, -0.29; p = 0.045), but was not significantly associated with loss of lung function over time (-1.07%pVC/year; 95%CI: -2.86, 0.71; p = 0.230). The presence of anti-Ro52 was significantly associated with the loss of lung function over time (-2.41%pVC/year; 95% CI: -4.28, -0.54; p = 0.013). Rate of loss of lung function increased linearly with increasing anti-Ro52 antibody levels (-0.03%pVC per arbitrary units/mL and year; 95%CI: -0.05, -0.02; p < 0.001). Immunohistochemical staining localized the Ro52 antigen to alveolar M2 macrophages in peripheral lung tissue both in subjects with and without SSc.Conclusions: This study suggests that antibodies targeting Ro52 are enriched in the lungs of patients with new-onset SSc-ILD, linking Ro52 autoimmunity to the pulmonary pathology of SSc. Clinical and immunohistochemical data corroborates these findings and suggest that anti-Ro52 may serve as a potential biomarker of progressive SSc-ILD.
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- Kerick, M., et al.
(författare)
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Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
- 2022
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Ingår i: npj Genomic Medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals. © 2022, The Author(s).
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- Kylhammar, David, et al.
(författare)
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Predicting mortality during long-term follow-up in pulmonary arterial hypertension
- 2021
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- The European Society of Cardiology (ESC) and European Respiratory Society (ERS) guideline recommendation of comprehensive risk assessments, which classify patients with pulmonary arterial hypertension (PAH) as having low, intermediate or high mortality risk, has not been evaluated during long-term follow-up in a “real-life” clinical setting. We therefore aimed to investigate the utility of risk assessment in a clinical setting for up to 5 years post diagnosis.386 patients with PAH from the Swedish PAH Registry were included. Risk group (low/intermediate/high) and proportion of low-risk variables were investigated at 3-, 4- and 5-year follow-ups after time of diagnosis. In an exploratory analysis, survival rates of patients with low-intermediate or high-intermediate risk scores were compared.A low-risk profile was in multivariate Cox proportional hazards regressions found to be a strong, independent predictor of longer transplant-free survival (p<0.001) at the 3-, 4- and 5-year follow-ups. Also, for the 3-, 4- and 5-year follow-ups, survival rates significantly differed (p<0.001) between the three risk groups. Patients with a greater proportion of low-risk variables had better (p<0.001) survival rates. Patients with a high-intermediate risk score had worse survival rates (p<0.001) than those with a low-intermediate risk score. Results were similar when excluding patients with ≥3 risk factors for heart failure with preserved ejection fraction, atrial fibrillation and/or age >75 years at diagnosis.Our findings suggest that the ESC/ERS guideline strategy for comprehensive risk assessments in PAH is valid also during long-term follow-up in a “real-life” clinical setting.
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| 10. |
- Mattsson, M., et al.
(författare)
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Validity and reliability of the Swedish version of the Self-Efficacy for Managing Chronic Disease scale for individuals with systemic sclerosis
- 2022
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 51:2, s. 110-119
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo investigate aspects of validity and reliability of the Swedish version of the Self-Efficacy for Managing Chronic Disease (SEMCD-Swe) scale in systemic sclerosis (SSc).Method: A forward–backward translation procedure was used. Content validity was assessed through interviews with 11 people with SSc and 10 healthcare professionals. Construct validity, internal consistency, test–retest reliability, and floor and ceiling effects were evaluated in 104 SSc patients.Results: The content validity of the SEMCD-Swe was interpreted as satisfactory, but some adjustments were made to increase the understanding. Confirmatory factor analysis supported a single-factor structure. Moderate to strong correlations between the SEMCD-Swe and Scleroderma Health Assessment Questionnaire; Multidimensional Assessment of Fatigue; Patient Health Questionnaire-8 (rs = −0.4 to −0.7), and RAND-36 subscales (rs = 0.5 to 0.7) were found. Weak correlations were found between SEMCD-Swe and modified Rodnan skin score; and disease severity of peripheral vascular and lung (rs = −0.1 to −0.2) and kidney (rs = 0.1) systems (Medsger severity scale). Cronbach’s alpha was sufficient (0.85) and corrected item-to-total correlations were good (≥ 0.50). The intraclass correlation coefficient for the total score was sufficient (0.82). No floor or ceiling effects were found.Conclusion: Support for construct validity was indicated, as the SEMCD-Swe in SSc show a single-factor structure and is more strongly associated with pain, fatigue, depressive symptoms, interferences with daily activities, disability, and quality of life than with disease severity. Our results also indicate support for content validity and reliability. However, the responsiveness of the SEMCD-Swe needs to be tested.
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