Which abnormality is considered central to the pathogenesis of primary IgA nephropathy?
- A Defective glycosylation of IgA1 leading to galactose-deficient IgA1 that forms self-aggregates and immune complexes ✓
- B Monoclonal proliferation of plasma cells producing intact IgA molecules
- C Autoantibodies directed against the NC1 domain of the alpha-3 chain of type IV collagen
- D Complement factor H deficiency causing uncontrolled alternative pathway activation at the GBM
Correct answer: A. Defective glycosylation of IgA1 leading to galactose-deficient IgA1 that forms self-aggregates and immune complexes
Explanation
In primary IgA nephropathy, IgA1 molecules have aberrantly galactose-deficient hinge-region O-glycans. These molecules self-aggregate, are recognized as foreign by anti-glycan antibodies, and form circulating immune complexes that deposit in the glomerular mesangium, activating the lectin and alternative complement pathways. Option D describes C3 glomerulopathy, option C describes Goodpasture syndrome, and monoclonal IgA production describes myeloma related kidney disease rather than this polymeric, polyclonal process.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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