The aim of the studies described in this thesis is to come to better understanding of the anti-modified protein antibody (AMPA) response in rheumatoid arthritis (RA) and to investigate the origin... Show moreThe aim of the studies described in this thesis is to come to better understanding of the anti-modified protein antibody (AMPA) response in rheumatoid arthritis (RA) and to investigate the origin of this response at both the antibody and B cell level. This is relevant as such studies could give insights on how B cell tolerance in RA is breached and gives rise to autoreactive B cells and the production of autoantibodies. This knowledge is important for preventing the disease or defining potential targets to treat the disease. Show less
Anti-citrullinated protein antibodies (ACPA) are highly specific biomarkers for rheumatoid arthritis (RA). ACPA are predominantly of the immunoglobulin (Ig)G isotype and 90% of ACPA-IgG contains N... Show moreAnti-citrullinated protein antibodies (ACPA) are highly specific biomarkers for rheumatoid arthritis (RA). ACPA are predominantly of the immunoglobulin (Ig)G isotype and 90% of ACPA-IgG contains N-glycans in the variable domain. With the research in this thesis, we showed that this remarkably high frequency of N-glycans on secreted ACPA-IgG corresponds to a high frequency of N-glycosylation sites in full-length variable region B-cell receptor (BCR) transcripts of ACPA-expressing B cells. We looked at clonotypes and mutational analysis of the BCR sequences and studied the frequency, position and introduction of N-glycosylation sites that distinguish ACPA-expressing B cells in RA from other (antigen-specific) B-cells. Show less
