Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency inherited disorder characterized by defects in the integrin receptors of white blood cells that lead to impaired adhesion and chemotaxis. Clinically LAD is characterized by recurrent life-threatening infections of the skin, mouth, and respiratory tract, delayed umbilical cord separation, impaired pus formation, poor wound healing, persistent leukocytosis, and periodontitis. Usually the first signs occur in infancy or early childhood. Skin infections may evolve into large ulcers. Severe periodontitis is often present later in life and leads to early tooth loss. A lack of swelling, redness, heat, or pus is observed in the area of infection. These clinical features are due to defective leukocyte adhesion to endothelial cells, absence of transmigration into inflamed tissues as well as deficient phagocytosis and chemotaxis.
Management of leukocyte adhesion deficiency is focused on controlling infections and includes antibiotics. Hematopoietic cell transplantation represents the only cure for LAD, but gene therapy may be available in the future. Prognosis depends on the severity of the disease. Without hematopoietic stem cell transplantation, death in patients with severe LAD occurs from infection within the first two years of life, whereas patients with a moderate form of the disease have a better chance of surviving into adulthood. Survival rate after bone marrow transplantation is 75%.
LAD is caused by mutations in the ITGB2 gene on chromosome 21q22.3. This gene encodes the beta-2-integrin, CD18. It is essential for the migration of leukocytes from the blood vessels to sites of infection, which requires firm adhesion of leukocytes to the endothelium. Defects in the function of the protein, secondary to mutations in this gene, lead to an impaired step in the inflammatory process. As a result, patients show increased susceptibility to infection. Severity of the disease correlates with the degree of CD18 deficiency.