A 14-month-old boy has recurrent sinopulmonary infections and persistent diarrhea due to Cryptosporidium parvum. Serum IgG and IgA are markedly low while IgM is normal or elevated. Flow cytometry shows absent class-switched B cells and reduced germinal centers. The most likely defective molecule is:

• A Bruton tyrosine kinase (BTK)
• B The common gamma chain of cytokine receptors
• C CD40 ligand on activated T helper cells ✓
• D Adenosine deaminase (ADA)

Explanation

X-linked hyper-IgM syndrome results from CD40 ligand mutations on activated CD4 T cells. Without CD40L engagement of CD40 on C cells, class switching and affinity maturation fail, so patients make only IgM, cannot form germinal center reactions, and are susceptible to encapsulated bacteria, Pneumocystis jirovecii, and Cryptosporidium (which can cause sclerosing cholangitis). BTK defects block C-cell development entirely with absent mature C cells, unlike the normal C-cell numbers seen here.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.