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

Author(s):
Rombouts, Y.; Willemze, A.; Beers, J.J.B.C. van; Shi, J.; Kerkman, P.F.; Toorn, L. van; Janssen, G.M.C.; Zaldumbide, A. (0000-0001-6680-4456); Hoeben, R.C. (0000-0001-9443-8377); Pruijn, G.J.M.; Deelder, A.M.; Wolbink, G.; Rispens, T.; Veelen, P.A. van (0000-0002-7898-9408); Huizinga, T.W.J. (0000-0001-7033-7520); Wuhrer, M. (0000-0002-0814-4995); Trouw, L.A. (0000-0001-5186-2290); Scherer, H.U. (0000-0002-5700-5617); Toes, R.E.M. (0000-0002-9618-6414)
Published
2016
Publication type
Article / Letter to editor

Abstract

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.

Date issued
2016-03-01
Language
English
Publisher
BMJ PUBLISHING GROUP
Is part of
Annals of the Rheumatic Diseases (2016), Vol. 75, no. 3, p. 578-585
hdl
1887/99496
doi
10.1136/annrheumdis-2014-206598