A 30-year-old patient with Crohn disease shows transmural inflammation with non-caseating granulomas. Genetic susceptibility in Crohn disease is primarily linked to a loss-of-function mutation in which gene affecting bacterial sensing?

• A STAT3, encoding a JAK-STAT signalling transcription factor
• B IL-10 receptor, encoding the anti-inflammatory cytokine receptor
• C NOD2/CARD15, encoding a cytosolic muramyl dipeptide pattern recognition receptor ✓
• D ATG16L1, encoding an autophagy protein involved in xenophagy

Explanation

NOD2 (CARD15) encodes an intracellular pattern recognition receptor that senses muramyl dipeptide from bacterial cell walls and activates NF-kappaB for appropriate mucosal immune responses. Loss-of-function NOD2 variants (particularly Arg702Trp, Gly908Arg, Leu1007fsinsC) are the strongest and most replicated genetic risk factors for ileal Crohn disease; they impair clearance of bacteria from intestinal crypts and dysregulate granuloma formation. STAT3 and ATG16L1 are secondary susceptibility loci. IL-10 receptor mutations cause very-early-onset IBD.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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