title: Lessons from rare maladies:  leukocyte adhesion deficiency syndromes.
abstract: OBJECTIVE
  The leukocyte adhesion deficiency (LAD) syndromes are rare genetically determined conditions with challenging clinical features. These immunodeficiencies also provide insights that are broadly relevant to the biology of leukocytes, platelets, intercellular interactions, and intracellular signaling. Recent discoveries merit their review in the context of existing knowledge.
  
  
  RESULTS
  New activities of β(2) integrins, which are deficient or absent in LAD-I, and new β(2) integrin-dependent functions of neutrophils and other leukocytes have recently been identified. Genetic defects and mechanisms accounting for impaired fucosylation of selectin ligands and defective selectin binding and signaling in LAD-II are now apparent. LAD-III, which presents with bleeding similar to that in Glanzmann thrombasthenia and platelet dysfunction in addition to impaired leukocyte adhesion, is now known to be due to absence of KINDLIN-3, a cytoplasmic protein that acts cooperatively with TALIN-1 in activating β(1), β(2), and β(3) integrins. Understanding of the leukocyte adhesion cascade and interactions of leukocytes with inflamed endothelium, which are impaired in each of the LAD syndromes, continues to be refined.
  
  
  CONCLUSIONS
  Although LAD syndromes are rare maladies, their investigation is generating new knowledge directly applicable to the diagnosis and care of patients and to fundamental paradigms in immunobiology and hemostasis.
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Estelle S
authors.initials: ES
authors.lastname: Harris
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Weyrich
authors.forename: Guy A
authors.initials: GA
authors.lastname: Zimmerman
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D006801:Humans; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D018821:CD18 Antigens