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Chapter 061. Disorders of Granulocytes and Monocytes (Part 8)

Disorders of Adhesion Two main types of leukocyte adhesion deficiency (LAD) have been described, LAD 1 and LAD 2. Both are autosomal recessive traits and result in the inability of neutrophils to exit the circulation to sites of infection, leading to leukocytosis and increased susceptibility to infection (Fig. 61-8). Patients with LAD 1 have mutations in CD18, the common component of the integrins LFA-1, Mac-1, and p150,95, leading to a defect in tight adhesion between neutrophils and the endothelium. The heterodimer formed by CD18/CD11b (Mac-1) is also the receptor for the complement-derived opsonin C3bi (CR3). The CD18 gene is. | Chapter 061. Disorders of Granulocytes and Monocytes Part 8 Disorders of Adhesion Two main types of leukocyte adhesion deficiency LAD have been described LAD 1 and LAD 2. Both are autosomal recessive traits and result in the inability of neutrophils to exit the circulation to sites of infection leading to leukocytosis and increased susceptibility to infection Fig. 61-8 . Patients with LAD 1 have mutations in CD18 the common component of the integrins LFA-1 Mac-1 and p150 95 leading to a defect in tight adhesion between neutrophils and the endothelium. The heterodimer formed by CD18 CD11b Mac-1 is also the receptor for the complement-derived opsonin C3bi CR3 . The CD18 gene is located on distal chromosome 21q. The severity of the defect determines the severity of clinical disease. Complete lack of expression of the leukocyte integrins results in a severe phenotype in which inflammatory stimuli do not increase the expression of leukocyte integrins on neutrophils or activated T and B cells. Neutrophils and monocytes from patients with LAD 1 adhere poorly to endothelial cells and protein-coated surfaces and exhibit defective spreading aggregation and chemotaxis. Patients with LAD 1 have recurrent bacterial infections involving the skin oral and genital mucosa and respiratory and intestinal tracts persistent leukocytosis neutrophil counts of 15 000-20 000 pL because cells do not marginate and in severe cases a history of delayed separation of the umbilical stump. Infections especially of the skin may become necrotic with progressively enlarging borders slow healing and development of dysplastic scars. The most common bacteria are Staphylococcus aureus and enteric gram-negative bacteria. LAD 2 is caused by an abnormality of fucosylation of SLex CD15s the ligand on neutrophils that interacts with selectins on endothelial cells and is responsible for neutrophil rolling along the endothelium. Infection susceptibility in LAD 2 appears to be less severe than in LAD 1. LAD 2 .