Leukocyte Adhesion Deficiency

 

Clinical Background

Leukocyte adhesion disorders (LAD) are a primary immune deficiency affecting phagocytic blood cells.

Epidemiology

  • Incidence – <1/1,000,000
  • Age – usually identified in infancy or early childhood

Inheritance 

  • Heterogeneous mutations in the CD18 leukocyte integrin gene
  • At least 3 defects known (LAD-I, LAD-II, LAD-III)
    • LAD I – integrin expression defect
    • LAD II – selectin defect
    • LAD III – defect in integrin activation
  • Autosomal recessive inheritance

Pathophysiology

  • Blood neutrophils are the first line of defense against bacterial and fungal infection
  • Initial neutrophil adherence is weak but becomes strong with the aid of beta integrin interactions
  • LAD involve defects in integrin expression leading to defective adhesion of neutrophils, leading to increased susceptibility to bacterial and fungal infections

Clinical Presentation

  • LAD I – characterized by delayed separation of the umbilical cord, recurrent soft tissue infections, chronic periodontitis, marked leukocytosis and lack of neutrophils in tissue infections
  • LAD II – same features as LAD I, but also growth and mental retardation abnormalities but with no delay in separation of umbilical cord
  • LAD III – same features as LAD I and severe bleeding tendency

Treatment

  • Early intervention for periodontal disease
  • Preventive antibiotics for infection
  • Allogeneic bone marrow transplant for severe disease