Mesangial IgA1 in IgA nephropathy exhibits aberrant O-glycosylation: Observations in three patients

Background. In IgA nephropathy (IgAN), circulating IgA1 molecules display a n abnormal pattern of O-glycosylation. This abnormality may potentially con tribute to mesangial IgA1 deposition, but this is unproven because the O-gl ycosylation of mesangial IgA1 has not been analyzed. Methods. IgA1 was eluted from glomeruli isolated from the kidneys of three IgAN patients obtained after nephrectomy or at postmortem. Serum from these patients, other patients with IgAN, and controls was subjected to the same treatment as the glomerular eluates. The O-glycosylation of eluted and ser um IgA1 was measured by lectin binding using an enzyme-linked immunosorbent assay-based system. Results. In all three cases, the lectin binding of IgA1 eluted from the glo meruli of IgAN patients was markedly higher than that of the serum IgA1 of the same individual, and also all but one of a series of serum IgA1 samples from other patients and controls. Conclusions. The higher lectin binding of glomerular compared with serum Ig A1 suggests that O-glycosylated IgA1 molecules abnormally and selectively d eposit in the kidney. These results provide the first evidence that mesangi al IgA1 is abnormally O-glycosylated, and support a direct role for abnorma l IgA1 O-glycosylation in the mechanism of mesangial IgA deposition in IgAN .