Progress in molecular and genetic studies of IgA nephropathy.
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.
Novak
J
J
Department of Microbiology, University of Alabama at Birmingham, 35294, USA. Jan_Novak@microbio.uab.edu
Julian
B A
BA
Tomana
M
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Mesteck
J
J
D000818:Animals; D018118:Chloride Channels / Q000276:immunology; D005690:Galactose; D005920:Glomerular Mesangium / Q000166:cytology; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology*; D011134:Polysaccharides / Q000096:biosynthesis
D018118:Chloride Channels; D007070:Immunoglobulin A; D011134:Polysaccharides; D005690:Galactose