Exploring seropositive rheumatoid arthritis: from immunological depths to clinical course

Abstract

In this thesis several aspects of the autoantibody response in patients with seropositive rheumatoid arthritis (RA) are investigated. Autoantibodies against post-translationally modified proteins (AMPA) are a hallmark of seropositive RA, of which anti-citrullinated protein antibodies (ACPA) are most well-known. In part 1 of this theses, we show Fc glycosylation of the ACPA B-cell receptor does not affect B-cell receptor signaling. However, Fc glycosylation is important for antibody function. In part 2, we investigated whether mucosal surfaces are in the AMPA response. For example, we showed AMPA IgA antibodies can be present in saliva of a small percentage of seropositive RA patients, but no AMPA were detected in faeces. Furthermore, the association between the AMPA profile and clinical phenotype of patients is explored in part 3. We found that patients with a broad AMPA profile differ at presentation compared to patient with a smaller autoantibody profile, but within the seropositive RA group, the breath of the autoantibody response was not associated with the chance of reaching drug-free remission.