Coeliac disease enteropathy graded by Marsh classification: Marsh 3c lesion indicates complete villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes. Which HLA haplotype combination carries >90% of the population-attributable risk for coeliac disease?
- A HLA-B27 and HLA-DR3
- B HLA-A2 and HLA-DR4
- C HLA-DQ2 (encoded by DQA1*05/DQB1*02) and HLA-DQ8 (DQA1*03/DQB1*0302) ✓
- D HLA-DR2 and HLA-DQ6
Correct answer: C. HLA-DQ2 (encoded by DQA1*05/DQB1*02) and HLA-DQ8 (DQA1*03/DQB1*0302)
Explanation
Coeliac disease requires the permissive HLA-DQ2 heterodimer (encoded on the same chromosome as DQA1*0501 and DQB1*0201) or HLA-DQ8 (DQA1*03/DQB1*0302). HLA-DQ2 is present in ~90% of coeliac patients; DQ8 accounts for most of the remainder. These molecules present deamidated gliadin peptides (modified by tissue transglutaminase, tTG2) to CD4+ T cells in the lamina propria, driving the autoimmune response. A negative HLA-DQ2 and DQ8 essentially rules out coeliac disease.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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