IgG glycosylation in autoimmune-prone strains of mice

Abstract

SLIMMARYThe relationship between increased levels of IgG oligosaccharide chains lacking galactose (GO) and the development of rheumatoid arthritis is unclear. In order to further our understanding oflhe observed correlation between raised serum GO and arthritis, we have studied GO levels in arthritisprone and non-susccptibic (i,c. non-arthrilis-prone) mice and the effects on GO of myeobacterial antigens, which have been postulated to play a role in the early events leading to the development of arthritis. We have shown that different age-matched mouse strains have characteristic "resting" levels of GO which (in six out of seven strains of mice) increase with age. We have also shown thai these increases can be enhanced by immunization of arthritis-prone strains of mice wilh an adjuvant containing mycobacteria (Freund's cotnplete adjuvant (FCA)). suggesting that deflects in the ability to regulate these GO changes tnay be related to susceptibility to arthritis.

N-glycomic biomarkers of biological aging and longevity: A link with inflammaging

“…A correlation between agalactosylated IgG and aging was observed also in mouse models. In fact, a marked tendency to agedependent increase of IgG-G0 was observed in all seven mice strain examined between 2-8 months of age (Bodman et al, 1994). A more recent study described a clear age-related increase of agalactosylated N-glycans in full serum in inbred mice housed in a specific pathogen free environment examined between 3-26 months of age (Vanhooren et al, 2011).…”

“…For example, arthritis induced by pristane administration in CBA/Igb mice (Rook et al, 1991a), or adjuvant treatment in Lewis rats (Yagev et al, 1993) was accompanied by a rise of IgG-G0. Moreover, in arthritis-prone MLR-lpr/lpr, disease was accompanied by an increase of IgG-G0 (Kuroda et al, 2001a), while in other arthritis prone mice strains arthritis and IgG-G0 rise were induced in parallel by the mere administration of complete Freund adjuvant (Bodman et al, 1994). The relationship between arthritis and IgG-G0 production was observed also in arthritis-prone HTLV-1 transgenic mice (Endo et al, 1993).…”

Analysis of Murine IgG Isotype Galactosylation in Collagen‐Induced Arthritis

“…We were unable to detect any increase in the percentage G0 (by direct sequencing) of IgG or its purified isotypes from DBA-1 mice with collagen induced arthritis compared to controls. This observation appears at variance with other ELISA based methods for detection of decreased IgG galactosylation utilizing anti-GlcNAc monoclonal antibodies or lectins in murine arthritis models [8,9,23] and deserves further comment. Various possibilities may explain this paradox:…”

“…Various techniques have been used to monitor this IgG galactose deficiency in both human diseases and arthritic animal models. These techniques include gas chromatographic quantitation of IgG monosaccharide residues [7], galactose and N-acetylglucosamine (GlcNAc) lectin based assays [8,9], anti-GlcNAc based ELISAs [4] and exoglycosidase sequencing of released N-linked oligosaccharides [10]. Each of these assays measure different glycosylation characteristics of IgG.…”