A 9-month-old boy has recurrent sinopulmonary pyogenic infections, Pneumocystis jirovecii pneumonia, and protracted Cryptosporidium diarrhea. Immunoglobulin levels: IgG 60 mg/dL, IgA undetectable, IgM 850 mg/dL. B-cell numbers are normal. The molecular defect lies in:

• A Activation-induced cytidine deaminase (AID)
• B CD40 on B cells
• C CD40 ligand (CD154) on activated CD4+ T cells ✓
• D CD19 on mature B cells

Explanation

X-linked hyper-IgM syndrome results from CD40L mutations on activated CD4 T cells. Without CD40L engagement of B-cell CD40, class switching and somatic hypermutation fail, so IgM stays high while IgG, IgA, and IgE fall, and germinal centers never form properly. Susceptibility to Pneumocystis reflects defective T-cell macrophage activation via CD40, and Cryptosporidium causes sclerosing cholangitis in these boys. AID defects produce an autosomal recessive phenotype with normal CD40L testing, and CD40 mutations give a similar but rarer picture.

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.