Which molecular abnormality is central to the current 'multi-hit' model of IgA nephropathy pathogenesis?
- A Monoclonal IgA produced by a single plasma cell clone that deposits in the mesangium
- B Galactose-deficient IgA1 with O-linked glycan defects in the hinge region, targeted by circulating antiglycan autoantibodies ✓
- C Defective alternative complement pathway regulation leading to uncontrolled C3 activation
- D Autoantibodies directed against the mesangial alpha-actinin antigen
Correct answer: B. Galactose-deficient IgA1 with O-linked glycan defects in the hinge region, targeted by circulating antiglycan autoantibodies
Explanation
The accepted model begins with genetically determined galactose-deficient IgA1 (Gd-IgA1) with aberrant O-linked glycans in the hinge region. Circulating antiglycan autoantibodies form immune complexes that deposit passively in the mesangium and activate complement. Option C describes C3 glomerulopathy, option A would suggest monoclonal gammopathy related disease, and option D is not part of the established model.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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