A 35-year-old man is found to have seronegative coeliac disease on small bowel biopsy (villous atrophy, increased IELs, crypt hyperplasia, Marsh grade IIIb) but anti-tTG IgA is negative. Total IgA is undetectable. What is the APPROPRIATE serological test in this setting?
- A Anti-gliadin IgA
- B Anti-tTG IgG ✓
- C Anti-reticulin antibody
- D Anti-endomysial IgA
Explanation
IgA deficiency occurs in 2–3% of coeliac disease patients and causes false-negative results with all IgA-based coeliac tests (anti-tTG IgA, anti-endomysial IgA). When selective IgA deficiency is confirmed, IgG-class antibodies — specifically anti-tTG IgG or anti-deamidated gliadin peptide (DGP) IgG — should be used for serological diagnosis. Anti-gliadin IgA is less specific and no longer recommended. Anti-reticulin antibody is outdated. Duodenal biopsy (as done here) remains the gold standard regardless of serological status.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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