Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis

Rombouts, Y.; Willemze, A.; Beers, J.J.B.C. van; Shi, J.; Kerkman, P.F.; Toorn, L. van; ... ; Toes, R.E.M. (2016)

Article / Letter to editor

yConclusions The vast majority of ACPA-IgG harbour N-glycans in their variable domains. As N-linked glycosylation requires glycosylation consensus sites in the protein sequence and as these are lacking in the 'germline-counterparts' of identified variable domains, our data indicate that the N-glycosylation sites in ACPA variable domains have been introduced by somatic hypermutation. This finding also suggests that ACPA-hyperglycosylation confers a selective advantage to ACPA-producing B cells. This unique and completely novel feature of the citrulline-specific immune response in RA elucidates our understanding of the underlying B cell response.

• All authors: Rombouts, Y.; Willemze, A.; Beers, J.J.B.C. van; Shi, J.; Kerkman, P.F.; Toorn, L. van; Janssen, G.M.C.; Zaldumbide, A.; Hoeben, R.C.; Pruijn, G.J.M.; Deelder, A.M.; Wolbink, G.; Rispens, T.; Veelen, P.A. van; Huizinga, T.W.J.; Wuhrer, M.; Trouw, L.A.; Scherer, H.U.; Toes, R.E.M.
• Date: 2016-03-01
• Journal: Annals of the Rheumatic Diseases
• Volume: 75
• Issue: 3
• Pages: 578 - 585
• DOI: doi:10.1136/annrheumdis-2014-206598