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Previous Volume 351:1409-1418 September 30, 2004 Number 14 Next

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ABSTRACT

Background 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.

Methods 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.

Results 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.

Conclusions Somatic heterozygous mutations of Fas can cause a sporadic form of ALPS by allowing lymphoid precursors to resist the normal process of cell death.

Source Information

From INSERM Unité 429 (E.H., C.V., M.-C.S., F.S., A.F., F.L.D., F.R.-L.) and Unité d'Immunologie–Hématologie Pédiatrique (A.-M.P., S.B., A.F.), Hôpital Necker–Enfants Malades, Paris; the Academic Unit of Child Health, Booth Hall Children's Hospital, Manchester, United Kingdom (P.D.A.); the Institute of Immunology, 2nd Medical School, Charles University, Prague, Czech Republic (E.H., J.B.); and the Unité d'Immuno-Hématologie, Hôpital Robert Debré, Paris (E.V.).

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