Leukocyte adhesion deficiency

Leukocyte adhesion deficiency (LAD) is a rare, autosomal recessive genetic disorder in which neutrophils fail to mobilize and migrate to sites of injury. At least three genetically distinct forms of this group of disorders have been described: LAD I, II, and III. Defects in the expression of beta2-integrins and fucose- containing proteins account for LAD-I and LAD-II, respectively. In LAD-III integrin expression by leukocytes is normal, but the integrins fail to generate high avidity for their cognate endothelial-cell ligands. Mutations in the KINDLIN3 (official symbol FERMT3), a gene that encodes an intracellular protein that interacts with cytoplasmic tails of beta-integrins in hematopoietic cells, is the cause of LAD-III. Dominant-negative mutations resulting in deficiency of ras-related C3 botulinum toxin substrate (Rac2), the predominant hematopoeitic-specific Rho GTPase in neutrophils also leads to leukocyte adhesion deficiency.