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IgA nephropathy (NORD)
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IgA nephropathy p. 620
Henoch-Schönlein purpura and p. 322
IgA is a class of immunoglobulin, or antibody, and nephropathy means kidney disease.
IgA is the main antibody found in breast milk, tears, saliva, and the mucosal secretions of respiratory tract, gastrointestinal tract, and the genitourinary tract.
Unlike other antibodies, IgA can be secreted out in pairs or a dimeric form called secretory IgA, which is literally two IgA antibodies attached together.
By being bound together, it helps both antibodies avoid degradation by proteolytic enzymes in harsh environments like the gut.
Now, IgA comes in subclasses—IgA1 and IgA2, IgA1 is found mainly in the serum while IgA2 is more often found in the mucus secretions, typically in its dimeric form.
Now, the hinge region of the IgA1 heavy chain—the part that gives the antibody a bit of flexibility to bind multiple antigens without being torn apart—is made up of a string of amino acids.
Among these are serine and threonine residues which are O-linked glycosylated, meaning they have a sugar molecule, specifically galactose, attached to their oxygen.
Now these glycosylated IgA1 antibodies are identified by the body and degraded when too much of it accumulates.
In IgA nephropathy, though, there is abnormal glycosylation of these serine and threonine residues, causing them to be galactose-deficient.
In addition, it’s thought that these galactose-deficient IgA1 antibodies are different enough from normal IgA1 antibodies that the body no longer recognizes them as self.
These immune complexes can travel through the bloodstream where they get trapped at sites of filtration, like the kidney.
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