Humoral autoimmune response against specific collagen type II epitopes in Bulgarian patients with rheumatoid arthritis

Abstract

Collagen type II (CII) is a strong candidate autoantigen for rheumatoid arthritis (RA) pathogenesis. CII is the main structural protein of synovial cartilage and it is attacked by both antibodies and T-cells during RA disease course. Experiments with mouse models have identified an immunodominant T-cell epitope from CII as well as several epitopes that are recognized by the majority of CII-specific autoantibodies. It has been shown that some epitope-specific anti-CII antibodies are arthritogenic and are associated with development of chronic arthritis. In addition, the immunodominant CII epitopes could be posttranslationally modified and these modified epitopes might be involved in induction and/or perpetuation of autoimmune humoral response and arthritic pathology. The aim of the present study was to evaluate the CII epitope- specific humoral response in a subgroup of Bulgarian patients with rheumatoid arthritis. Our results demonstrate that RA patients have significantly increased levels of anti-CII antibodies compared to healthy individuals and patients with other type of autoimmune disease. The majority of anti-CII antibodies in Bulgarian patients are directed against the U1 and J1 conserved epitopes. We show that D8 epitope-specific antibodies react to the triple-helical structure of the epitope and thus recognize both the native and the posttranslationally citrullinated D8. This is the first article presenting an evaluation of CII-specific humoral autoimmune response in Bulgarian patients with rheumatoid arthritis.

Keywords

• rheumatoid arthritis
• autoimmune response
• collagen type II
• epitope-specific antibodies