The initial event proposed in the pathogenesis of primary IgA nephropathy is:

• A Deposition of preformed cryoglobulins in the glomerular mesangium
• B Formation of galactose-deficient IgA1 that is recognized by antiglycan antibodies, generating circulating immune complexes ✓
• C In situ binding of anti-GBM antibodies to the NC1 domain of type IV collagen
• D Uncontrolled activation of the alternative complement pathway due to factor H deficiency

Explanation

IgA nephropathy is driven by galactose-deficient IgA1 (Gd-IgA1). The exposed terminal N-acetylgalactosamine acts as an epitope, antiglycan autoantibodies bind it, and the resulting immune complexes deposit in the mesangium, activating complement via the alternative and lectin pathways. Option A describes mixed cryoglobulinemia seen in hepatitis C. Option C is anti-GBM disease. Option D underlies C3 glomerulopathy and atypical hemolytic uremic syndrome, not IgA nephropathy.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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