Agalactosyl IgG and Antibody Specificity in Rheumatoid Arthritis, Tuberculosis, Systemic Lupus Erythematosus and Myasthenia Gravis

Abstract

Agalactosyl IgG (Gal(0) is a glycoform lacking terminal galactose from the oligosaccharides situated on the Fc. The percentage of circulating IgG that is Gal(0) is increased in a a number of autoimmune diseases, and in certain chronic infections associated with autoantibody production. However it is not known whether this represents decreased galactosylation of all IgG, or an increase in the relative concentration of a subset of agalactosyl antibodies of specificity relevant to the disease process. Since there is currently no way to separate agalactosyl from galactosylated IgG, we devised an assay for the relative degree of galactosylation of antibody to tetanus toxoid (TT), an antigen irrelevant to the diseases studied, and compared this value with the %Gal(0) of the whole circulating IgG. In rheumatoid arthritis (RA) and tuberculosis (TB), a raised %Gal(0) in serum IgG was reflected in a parallel rise in the extent to which antibody to TT was agalactosyl. In SLE a rise in %Gal(0) was seen in the presence of very little rise in agalactosyl anti-TT, and in myasthenia gravis (MG), where serum %Gal(0) is normal, an abnormally low percentage of the anti-TT was agalactosyl. These results imply that in RA and TB a systemic influence is downregulating the galactosylation even of irrelevant IgG. However in SLE and MG antibodies of specificities not studied here must be responsible for the %Gal(0) found in serum. It remains to be seen whether these are the autoantibodies involved in the disease process.

Sialylated IgG-Fc: a novel biomarker of chronic inflammatory demyelinating polyneuropathy

“…Agalactosylated IgG has also been found to be elevated in systemic lupus erythematosus, Sjögren's syndrome, Crohn's disease, myasthenia gravis, Lambert-Eaton myasthenic syndrome and GBS 4 22 23. These studies suggested that IgG galactosylation plays a regulatory role in the anti-inflammatory reaction.…”

Sialylated Autoantigen-Reactive IgG Antibodies Attenuate Disease Development in Autoimmune Mouse Models of Lupus Nephritis and Rheumatoid Arthritis

“…Next we studied whether the serum IgG glycosylation differs between lupus-prone Fcgr2b −/− mice and 56R +/− Fcgr2b −/− mice. Autoimmune-prone MRL-Fas(lpr) mice and SLE patients show increased levels of pro-inflammatory agalactosylated (G0) IgGs in serum, compared to healthy controls ( 8 , 12 , 15 ). In line with that, serum IgG Abs from lupus-prone Fcgr2b −/− mice were less sialylated, compared to wild-type controls (Figures 3 C,D; Figure S1 in Supplementary Material).…”

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

“…In a 1985 study (Parekh et al, 1985), it was shown for the first time that IgG from both rheumatoid arthritis (RA) and primary osteoarthritis patients exhibited an increased level of short N-linked oligosaccharides, chains terminated by N-acetylglucosamine [reviewed in Parekh et al, 1989;Rademacher et al, 1988;Rademacher, 1991]. Successively, the presence of agalactosylated N-linked chains was found to be associated with different autoimmune diseases (Axford et al, 2003;Isenberg, 1995;Pilkington et al, 1995b;Martin et al, 2001), as summarized in Table 3.…”