Background Impaired Fas-induced apoptosis of lymphocytes invitro is a principal feature of the autoimmune lymphoproliferativesyndrome (ALPS). We studied six children with ALPS whose lymphocyteshad normal sensitivity to Fas-induced apoptosis in vitro.
Methods Susceptibility to Fas-mediated apoptosis and the Fasgene were analyzed in purified subgroups of T cells and othermononuclear cells from six patients with ALPS type III.
Results Heterozygous dominant Fas mutations were detected inthe polyclonal double-negative T cells from all six patients.In two patients, these mutations were found in a fraction ofCD4+ and CD8+ T cells, monocytes, and CD34+ hematopoietic precursors,but not in hair or mucosal epithelial cells.
Conclusions Somatic heterozygous mutations of Fas can causea sporadic form of ALPS by allowing lymphoid precursors to resistthe 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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