IL-12 Receptor Deficiency

Summary

Interleukin-12 Receptor (IL-12R) Deficiency is an autosomal recessive immunodeficiency disorder characterized by a mutation in the gene encoding receptors for Interleukin-12 (IL-12) on T-cells.  Since IL-12 signalling is required for naive Helper T-cells to differentiate into the Th1 effector cell line, these patients have a decreased Th1 response. This decreased Th1 response reduces interferon-gamma signalling, which impairs the activation of macrophages. Decreased Th1 response also impairs downstream Cytotoxic T-cell and Natural Killer (NK) cell responses against intracellular pathogens. Ultimately, patients with IL-12 receptor deficiency are susceptible to infections by intracellular organisms, including mycobacteria (tuberculosis) and salmonella.

Key Points

• Interleukin-12 Receptor (IL-12R) Deficiency
  • Decreased Th1 cell response
    • Signalling by Interleukin-12 (IL-12) required for differentiation into Th1 by naive Helper T-cells
  • Decreased Interferon gamma (IFN-γ) production by Th1 cells
    • Reduces activation of Macrophages against threats
    • Reduces Cytotoxic T-cell and Natural Killer (NK) cell activity against intracellular threats
  • Autosomal Recessive
  • Immunodeficiency
    • Disseminated infections from intracellular organisms
      • Mycobacteria
        • e.g. following administration of BCG vaccine
      • Salmonella