• Definition: impaired Th1 response due to ↓ IL-12 receptors
• Etiology: autosomal recessive
• Pathophysiology
  • Normally, antigen-presenting macrophages release IL-12 → Th cells transformation to T1 type → release of IFN-γ to activate macrophages
  • Defective IL-12 receptors: macrophages cannot be activated by IFN-γ → no cytotoxicity in cells infected with intracellular pathogens (e.g., Mycobacteria, Salmonella)
  • IL-12 receptor deficiency is the underlying pathology in most cases of high Mendelian susceptibility to mycobacterial disease (MSMD)
    • Affected individuals have defects in IFN-γ mediated immunity.
    • This increases susceptibility to infection with weakly virulent mycobacteria (e.g., environmental mycobacteria, BCG vaccine).
• Clinical features
  • The age of onset varies (depends on the age at exposure to causative pathogens): ∼ 1–3 years of age
  • Features of disseminated disease
    • Mycobacterial infections (e.g., developing tuberculosis after BCG vaccination)
    • Fungal infections
• Diagnosis: ↓ IFN-γ
• Treatment: antibiotics and IFN-γ therapy