O-Linked Oligosaccharides in the Hinge Region of Immunoglobulin A1 and Their Involvement in IgA Nephropathy

Abstract

IgA nephropathy is a disease characterized by IgA deposits in the renal glomerular mesangium, quite frequently occurring as primary glomerulonephritis and in about 40% of patients in Japan, develops into renal failure within 20 years. The mechanism for the deposition of IgA is still unclear, although the IgA immune complex (IgA-IC) has been detected in glomerular deposits and serum of patients with IgA nephropathy. IgA deposits being a prominent feature of the disease, definite diagnosis can be made by renal biopsy.
Considerable study has been undertaken to identify the specific antigen for IgA-IC. The selective deposition of the IgA1 subclass in IgA nephropathy has been reported and structural disorder of the IgA1molecule appears to be a likely explanation for selective deposition. Characteristic structural differences in the two subclasses, IgA1 and IgA2, were examined in the hinge region of the IgA1 subclass which contains a mucin-like structure having O-linked oligosaccharides. The aberrant sugar chain of IgA1 from IgA nephropathy patients has been studied extensively. In this minireview, the structures and functions of mucin-type oligosaccharides in the IgA1 hinge region are summarized and possible involvement in the pathogenesis of this disease is discussed.