STRUCTURAL HETEROGENEITY OF GLYCANS IN IGA MOLECULES - IMPLICATIONS FOR IGA NEPHROPATHY

The carbohydrate moieties on glycoproteins, including immunoglobulins (Ig), are involved in a broad spectrum of biological functions. As rev ealed by enzymatic or chemical removal of carbohydrate moieties, inhib ition of glycosylation, or site-directed mutagenesis of asparagine res idues to prevent N-linked glycosylation, carbohydrates on Ig have been shown to participate in binding, internalization and catabolism by he patocytes or other cells, binding to Fc receptors on phagocytic cells, activation of complement, and opsonization. The structure of human Ig A1 is unique among all Ig. The heavy chain contains a hinge region wit h a characteristic primary structure not seen in any other Ig. and whi ch contains five short O-linked oligosaccharide side-chains composed o f serine-linked N-acetylgalactosamine (GalNAc) and beta 1-3-linked gal actose (Gal). Both of these monosaccharides may be sialylated. In cont rast to ubiquitous N-linked sidechains, O-linked carbohydrate moieties are found rarely among human serum glycoproteins. We have demonstrate d that IgA1 proteins from the sera of patients with IgA nephropathy (I gAN) are galactosylated to a lesser extent than those from healthy con trols. Decreased content of Gal and decreased reactivity of IgA from I gAN patients with lectins specific for GalNAc indicate that these stru ctural changes occur on glycans located in the hinge region of IgA1. T hus, in addition to rheumatoid arthritis, systemic lupus erythmatosus, inflammatory bowel disease and other disorders, IgA nephropathy may re present another example of a chronic disease in which aberrancies of c arbohydrates are observed and may participate in aetiopathogenesis.