Abberant Immunoglobulin G Glycosylation in Rheumatoid Arthritis by LTQ-ESI-MS

Abstract

Aberrant glycosylation has been observed in many autoimmune diseases. For example, aberrant glycosylation of immunoglobulin G (IgG) has been implicated in rheumatoid arthritis (RA) pathogenesis. The aim of this study is to investigate IgG glycosylation and whether there is an association with rheumatoid factor levels in the serum of RA patients. We detected permethylated N-glycans of the IgG obtained in serum from 44 RA patients and 30 healthy controls using linear ion-trap electrospray ionization mass spectrometry (LTQ-ESI-MS), a highly sensitive and efficient approach in the detection and identification of N-glycans profiles. IgG N-glycosylation and rheumatoid factor levels were compared in healthy controls and RA patients. Our results suggested that total IgG purified from serum of RA patients shows significantly lower galactosylation (p = 0.0012), lower sialylation (p < 0.0001) and higher fucosylation (p = 0.0063) levels compared with healthy controls. We observed a positive correlation between aberrant N-glycosylation and rheumatoid factor level in the RA patients. In conclusion, we identified aberrant glycosylation of IgG in the serum of RA patients and its association with elevated levels of rheumatoid factor.

Sialylated immunoglobulin G: a promising diagnostic and therapeutic strategy for autoimmune diseases

“…IgG1 and IgG2 sialylation also decreased in GPA, as confirmed by liquid chromatography coupled with mass spectrometry 57 . Su et al observed a negative correlation between the serum levels of total sialylated IgG and RF autoantibodies in RA patients, suggesting that sialylation levels may be promising serum biomarkers for RA disease activity and clinical diagnosis 59 .…”

Physiological and Pathological Inflammation Induced by Antibodies and Pentraxins

“…In addition to viral infections, aberrant glycosylation of antibodies has been described for several other disorders. These include a number of autoimmune diseases, such as RA [ 105 , 106 ] and MS [ 107 ]. In RA, these antibodies may promote inflammation through activation of synovial macrophages [ 32 , 34 ].…”

Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies

“…Their study showed that total purified IgG from RA has considerably lower galactosylation, lower sialylation, and higher fucosylation compared to that in healthy controls. Hence, in RA patients there should be a positive association between aberrant N-glycosylation and RF levels [ 93 ]. Recently, analysis of crystal structures of ACPA demonstrated that the V-domain glycans are positioned in the vicinity of the binding-pocket.…”

“…Their dynamic modeling has shown the potential of V-domain glycans to interact with the antigen-binding regions. It is noteworthy that human Ramos B-cells carrying V-domain glycosylated B-cell receptors (compared to their non-glycosylated counterparts) undergo increased signaling after stimulation [ 93 ]. Furthermore, glycan-based nanoparticles recently have been used to boost the immune system [ 94 ].…”