BackgroundGastrointestinal (GI) morbidity is prevalent in systemic sclerosis (SSc), causing a reduction in quality of life and increased mortality, but has been difficult to assess objectively [1]. Elevated levels of fecal calprotectin (F-cal), a biomarker of GI inflammation, has previously been observed in patients with SSc [2]. F-cal has not been explored in early SSc and its diagnostic potential in the classification of SSc has not been studied.ObjectivesOur objectives were; 1) study F-cal levels in early SSc; 2) investigate the discriminatory power of F-cal; 3) explore F-cal in relation to GI features of SSc.MethodsConsecutive referred patients with suspected new-onset SSc without concurrent non-SSc GI disease were invited to this study. Patients were classified as SSc if meeting ACR-EULAR criteria, or SSc mimickers if they did not. GI symptoms and use of NSAID or PPI was noted. F-cal was measured and levels >50ug/g were classified as elevated. F-cal was also measured in age- and sex matched controls without rheumatological disease.ResultsOf 137 patients, 92 were classified as SSc and 45 as SSc mimickers. Elevated F-cal was significantly more common in SSc patients compared to the control group (38% vs 7.3%; p < 0.001) but not compared to the SSc mimicker patients (38% vs 31%; p = 0.427). The median F-cal level was higher in SSc patients compared to controls (35 µg/g vs ≤30 µg/g; p ≤ 0.001) but not compared to the SSc mimicker patients (35 µg/g vs ≤30 µg/g; p = 0.248). Elevated F-cal was not associated with any GI symptoms. Elevated F-cal was more common in patients who used PPI (OR 7.14; 95% CI 2.56-29.93; p < 0.001).ConclusionIn this study, we demonstrate that elevated levels of F-cal are prevalent already in the early stages of SSc. These results are in line with previous data suggesting that GI involvement may be present in early SSc.Table 1.Frequency of GI features and association to F-cal elevation (n = 92)GI features (n, %)Normal F-cal, n = 57Elevated F-cal, n = 35Odds Ratio (95% CI)Dysphagia19 (35%)12 (34%)0.99 (0.41-2.41)Reflux symptoms33 (59%)23 (68%)1.46 (0.60-3.56)Fecal incontinence9 (16%)3 (8.6%)0.50 (0.08-2.22)Patient-reported involuntary weightloss11 (20%)8 (23%)1.21 (0.43-3.39)Dilated esophagus on HRCT8 (16%)8 (28%)1.95 (0.64-5.94)NSAID use12 (21%)6 (17%)0.78 (0.26-2.30)PPI use23 (40%)29 (83%)7.14 (2.56-19.93)Figure 1.F-cal measurements by group. Median value represented by horizontal bar.References[1]Frantz C et al. Impaired quality of life in systemic sclerosis and patient perception of the disease: A large international survey. Semin Arthritis Rheum 2016;46:115-23.[2]Marie I et al. Fecal calprotectin in systemic sclerosis and review of the literature. Autoimmun Rev 2015;14:547-54.AcknowledgementsThis study was funded by the Anna-Greta Crafoord Foundation, the Swedish Rheumatism Association, Stiftelsen Ulla och Roland Gustafssons Donationsfond.Disclosure of InterestsViggo Hamberg: None declared, Johan K Wallman Consultant of: Consultant of AbbVie, Amgen, Celgene, Eli Lilly, Novartis., Grant/research support from: Research support from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer., Elisabeth Mogard Consultant of: Consultant of Novartis, Elisabet Lindqvist: None declared, Tor Olofsson Consultant of: has performed consulting tasks for Merck Sharp & Dohme and for Eli Lilly, Kristofer Andréasson: None declared

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.

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 subjects with and without 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.

Objective To investigate the evolution of nailfold capillary density in patients with systemic sclerosis (SSc) in relation to immunosupressive treatment and autoantibodies. Methods Prospective study cohort. Consecutive newly diagnosed SSc patients were included into this study who, in a retrospective review, had at least 2 nailfold capillary microscopy (NCM) measurements performed during the first 48 months of follow-up. Capillary density per 3 mm was measured with widefield NCM. Improvement of capillary density per finger and mean capillary density were analysed. Longitudinal measurements of mean capillary density were analysed by generalized estimating equation (GEE). 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. Mycophenolate mofetil (MMF) was associated with less 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 GEE 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.