Which abnormality is considered the initiating event in the pathogenesis of IgA nephropathy?
- A Production of IgA1 with galactose-deficient O-linked glycans in the hinge region by mucosal B cells ✓
- B Formation of autoantibodies against the glomerular basement membrane
- C Stabilization of C3 convertase by autoantibodies (nephritic factors)
- D Selective IgA deficiency with compensatory IgM production
Correct answer: A. Production of IgA1 with galactose-deficient O-linked glycans in the hinge region by mucosal B cells
Explanation
IgA nephropathy begins with mucosal overproduction of galactose-deficient IgA1. These molecules are recognized as foreign, generating antiglycan autoantibodies; the resulting large circulating immune complexes deposit in the glomerular mesangium, activate the alternative complement pathway, and drive proliferation. Synpharyngitic hematuria reflects this mucosal linkage. Anti-GBM antibodies define Goodpasture disease, C3 nephritic factors define dense deposit disease, and selective IgA deficiency is a separate entity unrelated to the lesions of IgA nephropathy.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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