Insights into the origin of ACPAs in RA

The project aims to understand why citrullination is the most important target of antibodies in rheumatoid arthritis (RA) and the origin of anti-citrullinated protein antibodies (ACPAs). Preliminary studies suggest ACPAs may originate from antibodies targeting carbamylation. The overarching hypothesis is that ACPAs can arise during affinity maturation of germline encoded antibodies to carbamylated proteins. The proposal will use RA-derived monoclonal ACPAs to test this hypothesis. Successful work may uncover a mechanism for citrullinated protein immunogenicity and support germline encoded antibodies to carbamylated proteins as initial players in RA development.