Association of anti-SARS-COV-2 vaccine with increased incidence of myositis-related anti-RNA-synthetases auto-antibodies

INTRODUCTION: SARS-CoV-2 is a RNA virus that associates with heterogeneous clinical manifestations and complications. Auto-antibodies are identified in approximately 50% of hospitalized COVID-19 patients. OBJECTIVES: To determine the global incidence of myositis-related auto-antibodies (non Jo1-RNA synthetases: anti-PL7, anti-PL12, anti-EJ, anti-OJ and RNA-sensor: anti-MDA5) in our laboratory during COVID-19 pandemics, and to describe the clinical and laboratory features of these patients. STUDY DESIGN: A retrospective study was performed from 2015 to 2021 in a cohort of 444 patients with suspected inflammatory myopathy. The incidence of positive results for the MSA was expressed as absolute value per year for the reference population. Immunoblot analysis, indirect immunofluorescence and HLA typing of 36 patients with positivity for MSAs were collected and analyzed. RESULTS: We observed MSA positive in 28 patients in 2020 and 36 patients in 2021, representing a mean increase of 6-fold respect to previous years since 2015 (range, 0 to 19). In 2020, the most common antibody detected was anti-MDA5 (68%). In contrast, in 2021 the most common antibodies were anti-PL7 and/or anti-PL12 (69%). All patients in 2021 with positive anti-synthetases were fully vaccinated, 4 had previous documented infection, with median time from vaccine to MSA positivity of 5 months. Eight out of 36 patients (22%) reported clinical onset after SARS-CoV-2 vaccination and 6 out of 36 (17%) presented clinical and/or radiological worsening after SARS-CoV-2 vaccination. All patients presented with a known human leukocyte antigen (HLA)-DRB1* allele associated with ASS. The most prevalent alleles identified were DRB1*03:01, DRB1*04, DRB1*11:01, corresponding to 70% (16/23) of our cohort. CONCLUSIONS: Our preliminary data show an increased incidence of anti-synthetase antibodies during COVID-19 pandemic and SARS-CoV-2 vaccination associated to HLA DRB1* risk allele. Differential profiles of MSA specificities were observed: mainly against RNA-sensors in 2020 and against RNA-synthetases in 2021. Further studies are needed to support the association between SARS-CoV-2 infection and/or vaccination and the occurrence of this autoimmune syndrome.