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Objectives: The pro-inflammatory interleukin (IL)-17A serum has been characterized in several systemic autoimmune diseases, but not in antisynthetase syndrome (ASS). Therefore, the present study aims firstly to assess the serum level of the IL-17A in patients with ASS, comparing with healthy individuals, and secondly to analyze prospectively this IL in patients with refractory ASS undergoing rituximab treatment., Materials and Methods: A cross-sectional, single-center study that included 64 patients with ASS who were age-, gender-, and ethnicity-matched to 64 healthy individuals. Disease status was measured by the International Myositis Assessment and Clinical Studies Group (IMACS) set scores. Secondarily, the patients with refractory disease treated with rituximab were prospectively followed for 12 months. The IL-17A was assessed by the ELISA method., Results: The mean age of the patients was 44.8 ± 11.8 years, with a predominance of female gender and Caucasian. The median serum IL-17A level was higher in ASS patients compared with healthy individuals: 9.7 (9.1-10.4) vs. 7.7 (5.7-9.0) pg/mL, respectively, and P < 0.001. However, the demographical, clinical, and laboratory data indicates that disease status did not correlate with serum levels of the IL-17A in ASS patients. Prospectively, 16 patients received rituximab, and there was a drop of IL-17A serum level over the first year of treatment in these patients: from 9.7 (9.1-10.6) to 9.0 (8.2-9.7) pg/mL (P = 0.01)., Conclusions: Our study demonstrated that patients with ASS have increased serum levels of the IL-17A compared with healthy controls. In addition, the patients with refractory ASS treated with rituximab showed a reduction of the serum levels of the IL-17A. Key Points • Patients with ASS have increased serum levels of the IL-17A. • Patients with refractory ASS treated with rituximab showed a reduction of the serum levels of the IL-17A.