In IgA nephropathy, the initiating abnormality that sets off the disease cascade is best described as:
- A Autoantibodies directed against the NC1 domain of the alpha-3 chain of type IV collagen
- B Hereditary deficiency of complement factor H permitting uncontrolled alternative pathway activation
- C Defective O-glycosylation of the hinge region of IgA1 leading to galactose-deficient IgA1 ✓
- D Selective IgA deficiency with recurrent mucosal infections
Explanation
The current model holds that patients produce IgA1 with galactose-deficient O-linked glycans in the hinge region. These molecules are recognized by circulating antiglycan autoantibodies, forming immune complexes that deposit in the glomerular mesangium, activate the alternative complement pathway, and drive mesangial proliferation. Factor H deficiency underlies A3 glomerulopathy rather than IgA nephropathy, anti-COL4C3 antibodies cause anti-GBM disease, and selective IgA deficiency is not the mechanism, since most deficient individuals never develop glomerulonephritis.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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