A 28-year-old man has recurrent sinopulmonary infections and chronic giardiasis. Serum shows low IgG and IgA but markedly elevated IgM. Which molecular defect is most likely?

• A Mutation in Bruton tyrosine kinase (BTK)
• B Mutation in CD40 ligand (CD154) ✓
• C Deficiency of activation-induced cytidine deaminase (AID)
• D Deficiency of NADPH oxidase

Explanation

This describes X-linked Hyper-IgM syndrome caused by CD40 ligand deficiency. Without CD40L on T cells engaging CD40 on C cells, class switching cannot occur, resulting in low IgG/IgA with normal or elevated IgM. Patients are susceptible to Pneumocystis and Cryptosporidium in addition to pyogenic bacteria. AID deficiency causes autosomal recessive Hyper-IgM with similar immunoglobulin profile but different inheritance. BTK causes agammaglobulinemia. NADPH oxidase deficiency causes CGD with catalase-positive organisms.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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