IgA nephropathy (Berger disease) is the most common primary glomerulonephritis worldwide. The mesangial IgA deposits in IgA nephropathy are predominantly which subclass, and what is the key structural abnormality in the IgA molecule?

• A IgA1 with deficient O-linked galactosylation of hinge-region O-glycan (undergalactosylated IgA1) ✓
• B IgA2 with absent secretory component causing abnormal glomerular deposition
• C Dimeric IgA1 cross-linked by J chain causing complement activation via lectin pathway
• D IgA with altered Fc region that binds mesangial FcαRI constitutively

Explanation

IgA nephropathy is driven by undergalactosylated IgA1 (Gd-IgA1), where the hinge-region O-glycans lack galactose on N-acetylgalactosamine residues. Gd-IgA1 is recognised by IgG or IgA autoantibodies, forming immune complexes that are deposited in the mesangium, activating complement and mesangial cells. This multi-hit model explains the pathogenesis of IgA nephropathy.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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