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 circulatin g Ige that is Gal(0) is increased in a a number of autoimmune diseases , and in certain chronic infections associated with autoantibody produ ction. However it is not known whether this represents decreased galac tosylation of all IgG, or an increase in the relative concentration of a subset of agalactosyl antibodies of specificity relevant to the dis ease process. Since there is currently no way to separate agalactosyl from galactosylated IgG, we devised an assay for the relative degree o f galactosylation of antibody to tetanus toroid (TT), an antigen irrel evant to the diseases studied, and compared this value with the %Gal(0 ) of the whole circulating IgG. In rheumatoid arthritis (RA) and tuber culosis (TB), a raised %Gal(0) in serum IgG was reflected in a paralle l 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 agala ctosyl anti-TT, and in myasthenia gravis (MG), where serum %Gal(0) is normal, an abnormally low percentage of the anti-TT was agalactosyl. T hese results imply that in RA and TB a systemic influence is downregul ating the galactosylation even of irrelvant 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 th e autoantibodies involved in the disease process.