Tolerance and immune regulation in rheumatoid arthritis

Abstract

The general aim of this

thesis was to elucidate the immune regulation and breach of tolerance towards

modified proteins in Rheumatoid Arthritis(RA). Anti-modified protein antibodies

are a hallmark of disease and are implicated in the pathogenesis of RA. Recent studies have shown that these autoantibodies can serve as diagnostic and prognostic biomarkers. Most research on the role of autoantibodies in RA has focused on ACPA, which are directed against citrullinated proteins. In the past several years it has become clear that the autoantibody response in RA extends to several other modified proteins, such as proteins modified by carbamylation and acetylation. As all these auto-antibodies recognize post-translationally modified proteins, these antibodies are collectively called anti-modified protein antibodies (AMPA). A variety of AMPAs against different protein modifications (anti-citrullinated, carbamylated and -acetylated protein antibodies) have now been described in RA suggesting a shared common ‘developmental’ basis. The studies described in these thesis aim to understand how autoreactive B cell responses are generated to post-translational modified proteins.