• Definition: A group of syndromes characterized by impaired interaction between Th cells and B cells that results in a B cell class-switching defect
• Epidemiology: CD40 ligand deficiency is the most common form.
• Etiology
  • X-linked recessive inheritance
  • CD40L deficiency in Th cells leads to abnormal interaction with B cells that express the CD40 receptor, disrupting B-cell class-switching, which leads to depleted immunoglobulins
    • Because CD40L is required for B-cells to undergo class-switching, mutations to CD40L generally cause B cells to overproduce IgM and dramatically underproduce other immunoglobulin classes (IgA, IgE, IgG)
• Clinical features
  • Recurrent severe pyogenic infections that manifest since childhood
    • Opportunistic sinopulmonary infections (commonly Pneumocystis jirovecii and Histoplasma)
    • Cryptosporidium enteritis (which may lead to biliary disease, cirrhosis, and cholangiocarcinoma)
    • CMV hepatitis
  • Failure to thrive
• Diagnosis
  • ↓ IgG, IgA, IgE
  • Normal or ↑ IgM
  • Lymph node biopsy: absent germinal centers