The initial pathogenic event proposed in IgA nephropathy involves which abnormality?
- A Deposition of galactose-deficient IgA1 with formation of autoantibodies against it ✓
- B Defective alternative pathway regulation causing uncontrolled C3 activation
- C Antibodies against the NC1 domain of the alpha-3 chain of type IV collagen
- D Impaired degradation of immune complexes by the mannose-binding lectin pathway alone
Correct answer: A. Deposition of galactose-deficient IgA1 with formation of autoantibodies against it
Explanation
The multihit model of IgA nephropathy begins with genetically determined overproduction of galactose-deficient IgA1 (Gd-IgA1). Circulating autoantibodies recognize this aberrant glycoform, forming immune complexes that deposit in the mesangium and activate complement via both lectin and alternative pathways. Uncontrolled alternative pathway activation with C3 consumption defines C3 glomerulopathy, not IgA nephropathy. Anti-COL4A3 NC1 antibodies cause anti-GBM disease.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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