IL-12 receptor deficiency
- 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
- Diagnosis: ↓ IFN-γ
- Treatment: antibiotics and IFN-γ therapy