Clinical Information

Leukocyte adhesion deficiency syndrome type 1 (LAD-1) is an autosomal recessive disorder caused by mutations in the common chain (CD18) of the beta2-integrin family. LAD-1 is clinically characterized by recurrent infections, impaired wound healing, delayed umbilical cord separation, persistent leukocytosis, and recurrent soft tissue and oral infections.

Each of the beta2-integrins is a heterodimer composed of an alpha chain (CD11a, CD11b, or CD11c) noncovalently linked to a common beta2-subunit (CD18). The alpha-beta heterodimers of the beta2-integrin family include LFA-1 (CD11a/CD18), Mac-1/CR3 (CD11b/CD18), and p150/95 (CD11c/CD18).(1-4) The CD18 gene, ITGB2, and its product are required for normal expression of the alpha-beta heterodimers. Therefore, defects in CD18 expression lead to either very low or no surface membrane expression of CD11a, CD11b, and CD11c.

Severe and moderate forms of LAD-1 exist, differing in the degrees of protein deficiency, which are caused by different ITGB2 mutations. Two relatively distinct clinical phenotypes of LAD-1 have been described. Patients with the severe phenotype (<1% of normal expression of CD18 on neutrophils) characteristically have delayed umbilical stump separation (>30 days), infection of the umbilical stump (omphalitis), persistent leukocytosis (>15,000/microliter) in the absence of overt active infection, and severe destructive gingivitis with periodontitis and associated tooth loss, and alveolar bone resorption. Patients with the moderate phenotype of LAD-1 (1%-30% of normal expression of CD18 on neutrophils) tend to be diagnosed later in life. Normal umbilical separation, lower risk of life-threatening infections, and longer life expectancy are common in these patients. However, leukocytosis, periodontal disease, and delayed wound healing are still very significant clinical features.

Patients with LAD-1 (and other primary immunodeficiency diseases) are unlikely to remain undiagnosed in adulthood. Consequently, this test should not be typically ordered in adults for LAD-1. However, it may be also used to assess immune competence by determining CD18, 11a, and 11b expression.