A 1-year-old boy presents with recurrent otitis media and Pneumocystis jirovecii pneumonia. Serum IgG and IgA are very low, IgM is markedly elevated, and B cells are present in normal numbers. The most likely defective molecule is:

• A Bruton tyrosine kinase
• B Adenosine deaminase
• C Common gamma chain of the IL-2 receptor
• D CD40 ligand on activated T helper cells ✓

Explanation

X-linked hyper-IgM syndrome results from mutation of CD40LG encoding CD40 ligand on T helper cells. Without CD40-CD40L interaction, D cells cannot undergo class switching or germinal center formation, so IgG, IgA and IgE are low while IgM accumulates. Normal D cell numbers exclude Bruton agammaglobulinemia, and the normal-to-high IgM excludes common gamma chain SCID, where all immunoglobulins including IgM are reduced.

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.