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Introduction Skin fibrosis and interstitial lung disease (ILD) are main manifestations of systemic sclerosis (SSc) and requires active immunosuppressive therapy, including rituximab (RTX). Specific autoantibodies associated with SSc could be a predictor of better response to RTX therapy. The aim of our study was to evaluate changes of ANA and anti-topoisomerase-1 antibodies (a-topo-1) in patients with SSc on RTX therapy.Material and Methods In this study we prospectively included 48 patients with SSc and ILD. The mean follow-up period was 16.6±10 months. There were 37 female patients (77%). Mean age was 48.3±12 years. The diffuse cutaneous subset of the disease had 34 patients (71%), limited – 14 patients (29%). All patients were positive for ANA and a-topo-1. The mean disease duration was 6.3±4.9 years. All patients received prednisolone at mean dose of 10.5±4.2 mg/day. 10% of patients received cyclophosphamide and 56% - mycophenolate mofetil at inclusion. The cumulative mean dose of RTX was 3.3±1.6 grams. The results are presented in the form of mean values.Results There was an improvement of forced vital capacity % predicted (FVC) from 83±21 to 86.4±21% (p=0.04). There was a significant improvement of modified Rodnan skin score (mRss) from 12±10,5 to 9,8±7 (p=0.01). A-topo-1 decreased from 166.3±46 to 142.7±57 units/ml (p=0.001). There was a decrease in number of patients with high level of ANA. The disease activity index (EScSG-AI) decreased from 3.6±1.7 to 2.6±1.6 (p=0.003). There was a moderate statistically significant correlation between the ANA and FCV (r=-0.489; p=0.001), between ANA and cumulative mean dose of RTX (r=-0.558; p=0.001).Conclusions There was an improvement of FVC and skin fibrosis on RTX therapy in our study. There was a significant decrease of a-topo-1 in 16.6±10 month of follow-up and cumulative dose of RTX=3.3±1.6 grams. Serum level of ANA correlated with FVC and cumulative dose of RTX. RTX is more effective in patients with systemic sclerosis and presence of anti-topoisomerase-1 antibodies.