Treatment with mycophenolate mofetil is associated with improved nailfold vasculature in systemic sclerosis.

OBJECTIVE: To investigate the evolution of nailfold capillary density in patients with SSc in relation to immunosuppressive treatment and autoantibodies. METHODS: This was a prospective study cohort. Consecutive newly diagnosed SSc patients were included into this study who, in a retrospective review, had at least two nailfold capillary microscopy measurements performed during the first 48 months of follow-up. Capillary density per 3 mm was measured with widefield nailfold capillary microscopy. Improvement of capillary density per finger and mean capillary density were analysed. Longitudinal measurements of mean capillary density were analysed by generalized estimating equation. RESULTS: Eighty patients (68 women, 12 men) met the inclusion criteria. The median follow-up time was 27 months. Twenty-eight patients had an improved capillary density in per-finger analysis. MMF was associated with fewer numbers of fingers that had worsened in capillary density. Anti-topoisomerase antibodies were associated with low mean capillary density. Anti-RNA polymerase III antibodies were associated with improvement and anti-centromere antibodies with worsening of capillary density in per-finger analysis. MMF treatment was associated with less steep capillary density decline in a moderated generalized estimating equation model including presence of anti-topoisomerase antibodies and the interaction of MMF with follow-up time. CONCLUSION: Nailfold capillary density improved over time in a substantial proportion of SSc patients. MMF treatment had a positive impact on the evolution of capillary density in these patients. SSc autoantibody phenotype may affect the capillary density development. The data support previous hypotheses that early immunosuppression may favourably affect vascular regeneration in SSc.

Anti-Ro52 positivity is associated with progressive interstitial lung disease in systemic sclerosis-an exploratory study.

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.

Elevated fecal levels of the inflammatory biomarker calprotectin in early systemic sclerosis.

Knowledge on gastrointestinal manifestations in early systemic sclerosis (SSc) is limited. We have investigated gastrointestinal inflammation in SSc at the time of diagnosis using the inflammatory biomarker Fecal calprotectin (F-cal). Consecutive patients with suspected SSc were characterized in relation to the 2013 classification criteria for SSc and classified as SSc or SSc-like disease. F-cal levels were measured with a polyclonal ELISA (Calpro A/S, Lysaker, Norway) and levels above 50 µg/g were considered elevated. F-cal levels were compared to those of control subjects without rheumatic disease. Of 137 patients with suspected SSc, 92 were classified as SSc and 45 as SSc-like disease. Median (interquartile range) disease duration among the SSc participants was 2.5 (1.2, 4.6) years. A substantial proportion of participants classified as SSc (35/92, 38%) and SSc-like disease (14/45, 31%) exhibited elevated F-cal compared to the control group (3/41, 7.3%; p < 0.001 and p = 0.007, respectively). Elevated F-cal was associated with proton pump inhibitor usage (OR 7.14; 95% CI 2.56-29.93; p < 0.001). We conclude that elevated F-cal is present in a subgroup of patients with SSc at the time of diagnosis, suggesting that that GI inflammation may be present in this patient group early in the disease course. F-cal did not exhibit potential to differentiate SSc from SSc-like disease.