A 26-year-old woman with chronic diarrhoea, bloating, and iron deficiency anaemia has a negative IgA anti-tissue transglutaminase test. Serum total IgA is undetectable (<7 mg/dL) while IgG levels are normal. Which next step gives the correct diagnostic route?

• A Exclude coeliac disease and investigate for IBS-dominant pathology
• B Repeat tTG-IgA after two months of gluten challenge
• C Perform HLA typing; absence of DQ2 and DQ8 confirms coeliac disease
• D Test IgG-based assays such as tTG-IgG or deamidated gliadin peptide IgG, followed by duodenal biopsy ✓

Explanation

Selective IgA deficiency occurs far more commonly in coeliac disease than in the general population and produces falsely negative tTG-IgA results. In such patients, IgG-based assays, either tTG-IgG or deamidated gliadin peptide IgG, retain sensitivity and should guide the decision to biopsy. Repeating an IgA assay is futile since the deficiency is usually lifelong. HLA DQ2 or DQ8 positivity is present in virtually all coeliacs, so it is useful to exclude the disease, never to confirm it.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.