Reversion mutations in patients with leukocyte adhesion deficiency type-1 (LAD-1).

Journal Article (Journal Article)

Leukocyte adhesion deficiency type-1 (LAD-1) is an autosomal recessive immunodeficiency caused by mutations in the beta2 integrin, CD18, that impair CD11/CD18 heterodimer surface expression and/or function. Absence of functional CD11/CD18 integrins on leukocytes, particularly neutrophils, leads to their incapacity to adhere to the endothelium and migrate to sites of infection. We studied 3 LAD-1 patients with markedly diminished neutrophil CD18 expression, each of whom had a small population of lymphocytes with normal CD18 expression (CD18(+)). These CD18(+) lymphocytes were predominantly cytotoxic T cells, with a memory/effector phenotype. Microsatellite analyses proved patient origin of these cells. Sequencing of T-cell subsets showed that in each patient one CD18 allele had undergone further mutation. Interestingly, all 3 patients were young adults with inflammatory bowel disease. Somatic reversions of inherited mutations in primary T-cell immunodeficiencies are typically associated with milder clinical phenotypes. We hypothesize that these somatic revertant CD18(+) cytotoxic T lymphocytes (CTLs) may have altered immune regulation. The discovery of 3 cases of reversion mutations in LAD-1 at one center suggests that this may be a relatively common event in this rare disease.

Full Text

Duke Authors

Cited Authors

  • Uzel, G; Tng, E; Rosenzweig, SD; Hsu, AP; Shaw, JM; Horwitz, ME; Linton, GF; Anderson, SM; Kirby, MR; Oliveira, JB; Brown, MR; Fleisher, TA; Law, SKA; Holland, SM

Published Date

  • January 1, 2008

Published In

Volume / Issue

  • 111 / 1

Start / End Page

  • 209 - 218

PubMed ID

  • 17875809

Pubmed Central ID

  • PMC2200806

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2007-04-082552


  • eng

Conference Location

  • United States