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-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.LUMC / Geneeskund
