THE ROLE of MOLECULAR MIMICRY in SARS-COV-2 RELATED AUTOIMMUNE RHEUMATIC DISEASES

ABSTRACT

Background: Several studies suggested that SARS-CoV-2 infection may induce autoantibodies related to autoimmune rheumatic diseases (ARD). Objectives: To determine whether polyclonal antibodies from SARS-CoV-2 unin-fected patients with ARDs cross-react with SARS-CoV-2 and vice versa. Methods: 90 sera positive at high-titres for 23 common autoantibodies (all sera stored before 2018), were tested for reactivity against proteins of SARS-CoV-2 (spike protein S1, nucleocapsid NC etc) by ELISA and CMIA. Vice versa, 10 monoclonal antibodies against S1 protein (most of them against RBD) were tested for autoantibody reactivity by indirect immunofuorescence, ELISA, immunoblot and dot/line immunoassays coated with different antigens. Ten post-COVID sera with high titers of anti-Spike abs were tested by ELISAs for reactivity against various autoantigens related to ARDs. Results: 88 out of 90 samples (%), were totally unreactive to SARS-CoV-2 proteins;2 sera, one anti-CCP and one anti-CENP reacted against S protein. All sera tested negative for neutralized abs against SARS-CoV-2. None of 10 sera from SARS-CoV-2 infected patients reacted with different autoantigens by molecular assays. None of the 10 monoclonal abs against S1 protein reacted with 23 different self-antigens. On HEp2 cells as substrate for IIF, 3 of the 10 monoclonal abs gave a low-titre coarse speckled pattern. No reactivity was found by IIFL using tissue substrates. Conclusion: Our data do not suggest a dominant role for molecular mimicry and immunological cross reactivity as a trigger of autoantibodies related to ARDs.