ABERRANT GLYCOSYLATION OF IGA FROM PATIENTS WITH IGA NEPHROPATHY

Despite the prominent role of IgA, particularly IgA(1), in the pathoge nesis of IgA nephropathy (IgAN), the precise role of this molecule in the process remains unclear. Four biotin-conjugated lectins in sandwic h-type enzyme-linked immunosorbent assays were devised to determine th e glycosylation profiles of total IgA and its subclasses. We took adva ntage of differential binding properties of these lectins to sugar res idues to dissect the oligosaccharide chains O-linked to the hinge and those N-linked to the Fc region of total IgA and IgA subclasses in 47 patients with IgAN and an equal number of controls. The proportion of sialylated IgA(1) was higher in patients compared with controls (p < 0 .02), whereas IgA(2) in patients appeared less well sialylated. A redu ction of galactose in pathological IgA as detected by RCA-I became sig nificant after treatment of the molecule with neuraminidase (p < 0.01) . Defective galactosylation was also observed for patient IgA(1) when it was probed with ECL, a lectin that has a specificity for Gal 1,4 N- acetylglucosamine groupings on N-linked oligosaccharides. The RCA and ECL results, therefore, suggest that increased sialylation on the IgA( 1) is on O-linked oligosaccharides in the hinge region. This was partl y confirmed by a small increase in the binding of PNA to IgA(1) from t he patient group. This lectin binds preferentially to Gal 1,3 N-acetyl galactosamine groups that are found on O-linked oligosaccharides.