Progress in molecular and genetic studies of IgA nephropathy

Several new findings emerged recently from biochemical, genetic, and molecu lar studies of patients with IgA nephropathy. It appears that immunoglobuli n A1-secreting cells of IgA nephropathy patients produce increased amounts of aberrantly glycosylated IgA1 in which the O-linked glycans in the hinge region are deficient in the content of galactose. The galactose-deficient I gA1 in the circulation is recognized by naturally occurring antibodies with anti-glycan specificity, and immune complexes are formed. These circulatin g immune complexes escape hepatic degradation and eventually are deposited in the kidney mesangium. Resident mesangial cells bind the IgA-containing i mmune complexes with the involvement of a novel IgA receptor and become act ivated. A familial form of IgA nephropathy has been linked to chromosome 6q 22-23. Recent progress in molecular analyses of IgA nephropathy thus define s this disease as an autoimmune process with a novel IgA mesangial receptor and certain genetically determined traits.