An 8-month-old boy has recurrent otitis media and pneumonia. Serum shows very low IgG and IgA with markedly elevated IgM, normal numbers of circulating B cells, and absent germinal centers in lymph nodes. T cells are normal in number. The genetic defect lies in:

• A The BTK gene on chromosome Xq22
• B CD40 ligand expressed on activated CD4 positive T cells ✓
• C The common gamma chain of cytokine receptors
• D RAG1 recombinase

Explanation

Hyper-IgM syndrome results from mutation of CD40 ligand (CD40L, encoded on Xq26) on activated helper T cells. Without CD40 engagement of CD40 on B cells, T cell dependent class switching and affinity maturation cannot occur, so germinal centers fail to form and patients produce only IgM. Normal B cell numbers exclude Bruton agammaglobulinemia, where BTK mutation arrests B cell development before the immature B cell stage. Common gamma chain defects cause X-linked SCID with profound T cell loss.

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.