Autoimmune Lymphoproliferative Syndrome with Somatic Fas Mutations

Charles University in Prague, Praha, Praha, Czech Republic
New England Journal of Medicine (Impact Factor: 55.87). 10/2004; 351(14):1409-18. DOI: 10.1056/NEJMoa040036
Source: PubMed


Impaired Fas-induced apoptosis of lymphocytes in vitro is a principal feature of the autoimmune lymphoproliferative syndrome (ALPS). We studied six children with ALPS whose lymphocytes had normal sensitivity to Fas-induced apoptosis in vitro.
Susceptibility to Fas-mediated apoptosis and the Fas gene were analyzed in purified subgroups of T cells and other mononuclear cells from six patients with ALPS type III.
Heterozygous dominant Fas mutations were detected in the polyclonal double-negative T cells from all six patients. In two patients, these mutations were found in a fraction of CD4+ and CD8+ T cells, monocytes, and CD34+ hematopoietic precursors, but not in hair or mucosal epithelial cells.
Somatic heterozygous mutations of Fas can cause a sporadic form of ALPS by allowing lymphoid precursors to resist the normal process of cell death.

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