Disorders of innate immunity [DS:H02525] Primary immunodeficiency disease [DS:H01725]
Description
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.
Category
Primary immunodeficiency
Brite
Human diseases [BR:br08402]
Immune system diseases
Primary immunodeficiency
H00099 Leukocyte adhesion deficiency
Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.