|Anderson, Donald - PHARMACIA/UPJOHN|
|Smith, C Wayne|
Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: January 1, 2001
Publication Date: January 1, 2001
Citation: ANDERSON, D.C., SMITH, W.C. LEUKOCYTE ADHESION DEFICIENCIES. BOOK CHAPTER. 2001. Interpretive Summary: This is a review of the most recent information on the molecular mechanisms of genetic white blood cell deficiencies in children that lead to life-threatening infections.
Technical Abstract: Aberrations in adhesive mechanisms account for several clinical syndromes that involve an increase in susceptibility to bacterial infection. Leukocyte adhesion deficiency I (LAD I) (MIM 116920) was the first to be defined at a molecular level; it results from mutations in CD18, the beta subunit of beta 2 integrins, leading to partial or complete absence of expression, or dysfunction of these integrins. In addition to their role in neutrophil emigration, these integrins serve additional functions in host defense against infection. LFA-1 is involved in costimulation of lymphocytes during antigen presentation. Mac-1 functions as a receptor for complement opsonized bacteria, enhancing phagocytosis and bactericidal mechanisms (e.g., enhanced reactive oxygen production). Patients with LAD I appear to fall into two phenotypes. The severe phenotype occurs when CD18 expression is absent or extremely low. These patients are subject to overwhelming, life-threatening bacterial infections. The moderate phenotype occurs when either CD18 expression is very low or CD18 integrins are dysfunctional. These patients exhibit increased susceptibility to bacterial infections, but most have survived to adulthood. Numerous CD18 mutations have been defined, and patients are often compound heterozygotes, with differing mutations from the maternal and paternal alleles.