Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Patterns of Immunoglobulin-G Glycosylation Distinguish Different Clinical Phenotypes of Antiphospholipid Antibody Positivity.
Tarelli1, Edward, Axford1, John S., Giles2, Ian, Pericleous2, Charis, Pierangeli3, Silvia S., Ioannou4, Yiannis, Rahman2, Anisur
Sir Joseph Hotung centre for Musculoskeletal diseases, St George's University of London, London, United Kingdom
Division of Medicine/Centre for Rheumatology Research, University College London, London, United Kingdom
University of Texas Medical Branch, Galveston, TX
University College London, London, United Kingdom
Polyclonal IgG and antiphospholipid (aPL) antibodies from patients with different clinical manifestations of the antiphospholipid syndrome (APS) have been shown to exert differential effects on signalling pathways and tissue factor activity in target cells. Interestingly, these biological effects were not distinguished by their degree of aPL binding which did not differ significantly between the different APS subgroups.
Given that glycosylation is known to influence the biological activity of IgG, and that changes in IgG glycosylation patterns have been shown to predict clinical manifestations for various autoimmune diseases, we examined whether differential glycosylation of IgG may be a factor in determining the observed differences in the mechanism of the effects of IgG from APS patients.
The glycosylation profile of IgG N-glycans, enzymatically released, from protein G purified IgG from four sets of 8 patients; APS with pregnancy morbidity (PM) alone (aPL+ PM), vascular thromboses (VT) alone (aPL+ VT), aPL+ve patients without APS (aPL+ APS-) and healthy controls (aPL- HC) was examined using Matrix Assisted Laser Desorption Ionisation Time-Of-Flight Mass Spectrometry (MALDI-TOF MS). IgG glycans were divided into three main groups based on the number of galactose residues: G0, G1 and G2. These biantennary complex glycans may be further modified by the presence/absence of fucose (F) and/bisecting N-acetylglucosamine (bis).
There were no significant differences in aPL binding between the different APS and aPL+ groups. In contrast, the glycosylation profile of IgG was found to be significantly different in the 4 groups examined (Figure). IgG from the APS patients had significantly higher ratios of total G0:G2 compared with the aPL+ APS- patients (p=0.038) and those from aPL- HC (p=0.002). On further, more detailed, analysis, the IgG from patients with VT, which showed the most marked difference in total G0:G2 ratio, could be differentiated from the PM group based on significant differences in the levels of G1F, G2, G2F and G1Fbis (p<0.05).
Our findings show that IgG from patients with diverse clinical manifestations of APS and aPL positive healthy controls exhibit differential patterns of glycosylation that were not predicted by differences in aPL binding. Therefore, these glycosylation differences, which include the degree of galactosylation as well as fucosylation, could be used as a biomarker to discriminate between patients with VT and PM, and may provide a better insight into the different mechanistic action of IgG in these patients.
To cite this abstract, please use the following information:
Tarelli, Edward, Axford, John S., Giles, Ian, Pericleous, Charis, Pierangeli, Silvia S., Ioannou, Yiannis, et al; Patterns of Immunoglobulin-G Glycosylation Distinguish Different Clinical Phenotypes of Antiphospholipid Antibody Positivity. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :14