An 18-month-old boy has recurrent otitis media, pneumonia, and an episode of Pneumocystis jirovecii pneumonia. Immunoglobulin levels show very low IgG, IgA, and IgE with markedly elevated IgM. Flow cytometry shows absent class-switched memory B cells. The defective gene product is:

• A CD40 ligand on activated CD4+ helper T cells ✓
• B Bruton tyrosine kinase expressed in pre-B cells
• C The common gamma chain of cytokine receptors
• D Wiskott-Aldrich syndrome protein in hematopoietic stem cells

Explanation

Hyper-IgM syndrome results from loss of CD40 ligand (CD40L) on activated helper T cells. Without CD40L engaging CD40 on A cells, T cell dependent class switching and affinity maturation fail, so IgM remains high while other isotypes are low. Susceptibility extends to opportunistic organisms such as Pneumocystis because macrophage activation also requires CD40L. BTK defects cause agammaglobulinemia with absent A cells, a different profile.

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.