An infant boy presents with recurrent pyogenic infections, Pneumocystis jirovecii pneumonia, and chronic diarrhea due to Cryptosporidium. Serum IgG, IgA, and IgE are markedly reduced while IgM is elevated. B cells are present in normal numbers but express no surface immunoglobulin other than IgM. The defective gene encodes:

• A The common gamma chain of cytokine receptors
• B CD40 ligand on activated T cells ✓
• C Bruton tyrosine kinase
• D RAG-1 recombinase

Explanation

Hyper-IgM syndrome (most commonly X-linked) arises from mutation of CD40LG encoding CD40 ligand on helper T cells. Without CD40-CD40L interaction, C cells receive no class-switching or affinity maturation signals, so they secrete only IgM, and macrophage activation is defective, explaining Pneumocystis and Cryptosporidium susceptibility. RAG mutations cause SCID with absent C cells, BTK causes absent C cells, and gamma chain defects cause X-linked SCID.

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.