Progress in molecular and genetic studies of IgA nephropathy

J Novak, BA Julian, M Tomana, J Mestecky - Journal of clinical …, 2001 - Springer
J Novak, BA Julian, M Tomana, J Mestecky
Journal of clinical immunology, 2001Springer
Several new findings emerged recently from biochemical, genetic, and molecular studies of
patients with IgA nephropathy. It appears that immunoglobulin 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 IgA1 in the circulation is recognized by naturally occurring antibodies
with anti-glycan specificity, and immune complexes are formed. These circulating immune …
Abstract
Several new findings emerged recently from biochemical, genetic, and molecular studies of patients with IgA nephropathy. It appears that immunoglobulin 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 IgA1 in the circulation is recognized by naturally occurring antibodies with anti-glycan specificity, and immune complexes are formed. These circulating immune complexes escape hepatic degradation and eventually are deposited in the kidney mesangium. Resident mesangial cells bind the IgA-containing immune complexes with the involvement of a novel IgA receptor and become activated. A familial form of IgA nephropathy has been linked to chromosome 6q22-23. Recent progress in molecular analyses of IgA nephropathy thus defines this disease as an autoimmune process with a novel IgA mesangial receptor and certain genetically determined traits.
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