Reversion mutations in patients with leukocyte adhesion deficiency type-1 (LAD-1).
Blood
; 111(1): 209-18, 2008 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-17875809
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T Citotóxicos
/
Síndrome de Deficiencia de Adhesión del Leucocito
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Antígenos CD18
/
Mosaicismo
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Blood
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos