Agalactosyl IgG and antibody specificity in rheumatoid arthritis, tuberculosis, systemic lupus erythematosus and myasthenia gravis.
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.
Pilkington
C
C
Department of Medical Microbiology, UCL Medical School, London.
Yeung
E
E
Isenberg
D
D
Lefvert
A K
AK
Rook
G A
GA
D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D005260:Female; D005690:Galactose / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D009157:Myasthenia Gravis / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
D007074:Immunoglobulin G; D013745:Tetanus Toxoid; C064155:agalactosyl IGG; D005690:Galactose