Altered glycan accessibility on native immunoglobulin G complexes in early rheumatoid arthritis and its changes during therapy.

Altered glycan accessibility on native immunoglobulin G complexes in early rheumatoid arthritis and its changes during therapy.

Clin Exp Immunol. 2017 May 16;:

Authors: Stümer J, Biermann MHC, Knopf J, Magorivska I, Kastbom A, Svärd A, Janko C, Bilyy R, Schett G, Sjöwall C, Herrmann M, Muñoz LE

Abstract
The goal of this study was to investigate the glycosylation profile of native IgG present in serum immune complexes in patients with rheumatoid arthritis (RA). To accomplish this, lectin binding assays, detecting the accessibility of glycans present on IgG-containing immune complexes by biotinylated lectins were employed. Lectins capturing fucosyl residues (AAL), fucosylated tri-mannose N-glycan core sites (LCA), terminal sialic acid residues (SNA) and O-glycosidically-linked galactose/N-acetylgalactosamine (GalNac-L) were used. Patients with recent-onset RA at baseline and after 3-year follow-up were investigated. We found that native IgG was significantly more often complexed with IgM, C1q, C3c and CRP in RA patients suggesting alterations of the native structure of IgG. The total accessibility of fucose residues on captured immune complexes to the respective lectin was significantly higher in patients with RA. Moreover, fucose accessibility on IgG-containing immune complexes positively correlated with the levels of antibodies to cyclic citrullinated peptides (anti-CCP). We also observed a significantly higher accessibility to sialic acid residues and galactose/GalNAc glyco-epitopes in native complexed IgG of patients with RA at baseline. While sialic acid accessibility increased during treatment, the accessibility of galactose/GalNAc decreased. Hence, successful treatment of RA was associated with an increase in the SNA/GalNAc-L ratio. Interestingly, the SNA/GalNAc-L ratio particularly rises after glucocorticoid treatment. In summary, this study shows the exposure of glycans in native complexed IgG of patients with early RA revealing particular glycosylation patterns and its changes following pharmaceutical treatment. This article is protected by copyright. All rights reserved.

PMID: 28509333 [PubMed - as supplied by publisher]

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