Glycosylation of random IgG distinguishes seropositive and seronegative rheumatoid arthritis

Abstract

The N-glycosylation of human immunoglobulins, especially IgGs, plays a critical role in determining affinity of IgGs towards their effector (pro- and anti-inflammatory) receptors. However, it is still not clear whether altered glycosylation is involved in only antibody-dependent disorders like seropositive rheumatoid arthritis (RA) or also in pathologies with similar clinical manifestations, but no specific autoantibodies like seronegative RA. The clarification of that uncertainty was the aim of the current study. Another study aim was the detection of specific glycan forms responsible for altered exposure of native glycoepitopes. We studied sera from seropositive RA (n = 15) and seronegative RA (n = 12) patients for exposure of glycans in native IgG molecules, followed by determination of specific glycans by capillary electrophoresis with laser-induced fluorescent detection (CE-LIF). Aged-matched groups of normal healthy donors (NHD) and samples of intravenous immunoglobulin IgG preparations (IVIG) served as controls. There was significantly stronger binding of Lens culinaris agglutinin (LCA) and Aleuria aurantia lectin (AAL) lectins towards IgG from seropositive RA compared to seronegative RA or NHD. CE-LIF analysis revealed statistically significant increases in bisecting glycans FA2BG2 (p = .006) and FABG2S1 (p = .005) seropositive RA, accompanied by decrease of bisecting monogalactosylated glycan FA2(6)G1 (p = .074) and non-bisecting monosialylated glycan FA2(3)G1S1 (p = .055). The results suggest that seropositive RA is distinct from seronegative RA in terms of IgG glycan moieties, attributable to specific immunoglobulin molecules present in seropositive disease. These glycans were determined to be bisecting GlcNAc-bearing forms FA2BG2 and FABG2S1, and their appearance increased the availability of LCA and AAL lectin-binding sites in native IgG glycoepitopes.

Glycosylation Biomarkers Associated with Age-Related Diseases and Current Methods for Glycan Analysis

“…Hence, pre-treatment of the sample is required to successfully characterise the full glycome. Regarding the determination techniques, a broad range of analytical platforms can be applied for the profiling, characterisation and analysis of glycans, being the most widely used liquid chromatography coupled with fluorescence detection (LC-FLR) [ 9 , 48 , 97 , 100 ], lectin-based microarray [ 50 , 82 , 85 ], capillary electrophoresis (CE) [ 58 , 71 , 118 ], matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) [ 52 , 75 , 92 , 112 ], LC-MS [ 23 , 24 , 49 , 96 ], DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) [ 19 , 22 , 74 , 79 ], ion mobility (IM) and NMR [ 93 ]. Several reviews focus exclusively on describing the available techniques used for glycan analysis [ 129 , 130 , 131 ].…”

The B-Cell-Specific Ablation of B4GALT1 Reduces Cancer Formation and Reverses the Changes in Serum IgG Glycans during the Induction of Mouse Hepatocellular Carcinoma

“…This shows that GP2 can be used as a serum tumor marker for the early monitoring of HCC. Monogalactosylated G1(GP4 + 5) also plays a role in the differential diagnosis of diseases [ 28 ]. However, B4GALT1 gene knockout did not significantly affect its relative abundance.…”

Immunoglobulin G N-glycan Biomarkers for Autoimmune Diseases: Current State and a Glycoinformatics Perspective

“…The largest number of differential studies of IgG N-linked glycosylation in biomarker research published in the last 40 years is focused on rheumatic autoimmune diseases and, in particular, on rheumatoid arthritis [53][54][55][56][57][58][59][61][62][63][64][65][66][67][68][69][70][71][72]74,75,77,79,80,82,88,[121][122][123], systemic lupus erythematosus [56,59,62,64,73,74,[91][92][93]124], and, to a lesser extent, on Sjogren syndrome [59,63,73,74] and ANCA-associated systemic vasculitis [97][98][99][100][101][102]…”