Studies on the role of alpha enolase as a candidate autoantigen in pristane-induced arthritis and immunological tolerance of citrullinated type II collagen

Abstract: Rheumatoid Arthritis is a symmetric polyarticular disease, which mainly targets the synovial membrane, cartilage and bone of small diarthrodial joints of hand and feet. The etiology of rheumatoid arthritis remains uncertain. Pristane‐induced arthritis in the DA rat is a widely used experimental arthritis model. The mechanisms involved in arthritis development are not known. PIA is MHC class II associated and CD4+ T cells can transfer the disease to naïve recipients. As in human RA the autoantigens driving the joint inflammation are not yet known. In our lab, the immune responses against ubiquitously expressed RNA binding protein hnRNP‐A2 (RA33), cartilage specific rat CII and CXI as candidate autoantigens in PIA were studied. In the present study, we investigated the immune responses to the tissue non‐specific antigen α‐enolase. In my thesis, the first chapter shows the immune response against α‐enolase as autoantigen. The MHC dependency and association was assessed in MHC congenics rats. The results obtained will be useful to understand the T cell pathology in PIA and RA. In the second chapter of my thesis we discuss immune tolerance towards a cartilage specific autoantigen, mouse CII (mCII). The mCII expression in the thymus was studied. From the obtained data two hypotheses of tolerance breakage can be drawn. According to one hypothesis, the CII expressed in the thymus undergo post‐translational modification and gets converted into citrullinated CII by the PAD enzymes. The citrullinated CII undergo tolerization and the T cells in the periphery come into contact with native CII in joints and recognize it as foreign. Therefore, the T cells invoke autoimmune response against the native CII in joint. In another hypothesis, the T cells get tolerized towards native CII expressed in thymus. The T cells in the periphery are presented with neoepitopes in the joints, e.g. due to citrullination of CII in joints. This condition elicits the immune response towards citrullinated CII in joints.