Immunodeficiency, Innate System

Immunodeficiency, Innate System

 

Human primary immunodeficiencies that are associated with impaired innate immunity (nuclear factor kappa B signaling) are ectodermal dysplasia (X-linked or autosomal dominant) and interleukin-1 receptor associated kinase 4 (IRAK-4) deficiency.

Epidemiology

  • Incidence
    • Ectodermal dysplasia – 1/100,000 births
    • IRAK – rare; <30 affected individuals worldwide as of 2006

Inheritance

  • All are familial syndromes
  • Ectodermal dysplasia with immunodeficiency (EDA)
    • X-linked inheritance with NEMO mutation (AD-EDA) – also called hypohidrotic ectodermal dysplasia
  • IRAK-4 deficiency
    • Autosomal recessive inheritance

Pathophysiology

  • IRAK
    • IRAK 4 – plays an essential role in Toll-like receptor and IL-1 receptor mediated signaling
    • Broad defect in nuclear factor kappa B signaling with impaired Toll-like receptor function
    • Toll-like receptors function as recognition factors for microbial and viral ligands, enabling innate immunity to induce appropriate pathways to prevent infection
  • EDA
    • Abnormal development of 2 or more structures derived from the ectodermal layer
    • Most common is hypohidrotic dysplasia
  • Patients with these defects have otherwise normal immune systems and no difficulty with viral or other bacterial infections

Clinical Presentation

  • Severe recurrent infections occur in both deficiencies
    • EDAs (AD and XL)
      • Abnormal teeth (anodontia, hypodontia or cone/peg-shaped), hypohidrosis, hypotrichosis, cranial abnormalities, sparse hair
      • Particular susceptibility to encapsulated bacterial infections
      • Failure to thrive
    • IRAK-4
      • Normal appearance
      • Particular susceptibility to S. pneumoniae and S. aureus
        • All invasive infections occur before age 14

See Also