Rheumatoid arthritis antibody repertoire sequencing

Anti-citrullinated protein antibodies (ACPA) are a hallmark of rheumatoid arthritis (RA). While epitope spreading and polyreactivity of the overall serum ACPA response is believed to contribute to RA pathogenesis, little is understood regarding how this phenomenon occurs. We sequenced the antibody repertoires of individuals with RA to gain insight into the mechanisms leading to epitope spreading and polyreactivity of the serum ACPA response in RA. In particular, we used citrullinated peptide tetramers to identify ACPA-producing plasmablasts in patient blood, sorted all plasmablasts, and sequenced paired heavy and light antibody chains for each cell.