Glycan profiling of anti-citrullinated protein antibodies (ACPA) isolated from human serum and synovial fluid

Scherer, H.U.; Woude, D. van der; Ioan-Facsinay, A.; Bannoudi, H. el; Trouw, L.A.; Wang, J.; ... ; Toes, R.E.M. (2010)

Other

OBJECTIVE:: Anti-citrullinated protein antibodies (ACPA) exhibit unique specificity for RA. Whether and how ACPA contribute to disease pathogenesis, however, is incompletely understood. The Fc part of human IgG carries two N-linked glycan moieties which are crucial for the structural stability of the antibody and modulate its binding affinity to Fcgamma receptors and its ability to activate complement. We have purified ACPA from serum and synovial fluid and analyzed Fc glycosylation profiles in a specific manner. METHODS:: ACPA were isolated by affinity purification using cyclic citrullinated peptides as antigen. IgG(1) Fc glycosylation was analyzed by mass spectrometry. ACPA glycan profiles were compared to glycan profiles of total serum IgG(1) obtained from 85 well-characterised patients. Glycan profiles of paired synovial fluid and serum samples were available from 11 additional patients. RESULTS:: Compared to the pool of serum IgG(1), ACPA IgG(1) lack terminal sialic acid residues. In synovial fluid, ACPA are highly agalactosylated and lack sialic acid residues, a feature that was not detected for total synovial fluid IgG(1). Moreover, differential ACPA glycan profiles were detected in RF-positive versus -negative patients. CONCLUSION:: ACPA IgG(1) exhibit a specific Fc-linked glycan profile which is distinct from total serum IgG(1). Moreover, Fc glycosylation of ACPA differs markedly between synovial fluid and serum. As Fc glycosylation directly affects the recruitment of Fc-mediated effector mechanisms, these data could further our understanding of the contribution of ACPA to disease pathogenesis.

• All authors: Scherer, H.U.; Woude, D. van der; Ioan-Facsinay, A.; Bannoudi, H. el; Trouw, L.A.; Wang, J.; Haupl, T.; Burmester, G.R.; Deelder, A.M.; Huizinga, T.W.J.; Wuhrer, M.; Toes, R.E.M.
• Date: 2010-02-22
• Title of host publication: Arthritis and Rheumatism
• DOI: doi:10.1002/art.27414