Leukocyte Adhesion Deficiency

Leukocyte Adhesion Deficiency

 

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)
  • 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
    • Which then leads to increased susceptibility to bacterial and fungal infections
  • LAD I – integrin expression defect; LAD II – selectin defect; LAD III – defect in integrin activation

Clinical Presentation

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

Diagnosis

  • Laboratory testing
    • CBC reveals leukocytosis with neutrophilia (even in the absence of infection but exaggerated during infection)
    • Flow cytometric analysis
      • CD11b and CD18 expression on leukocytes
        • No expression – 75% die in infancy
        • 1-10% – 33% survive to age 40 years
        • >10% – mild deficiency which may not be recognized until late teen years

Differential Diagnosis

  • Neutropenic syndromes
  • Agranulocytosis
  • IRAK-4 deficiency
  • Job syndrome
  • Chronic granulomatous disease

Treatment

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

See Also