Autoimmune lymphoproliferative syndrome with somatic Fas mutations.
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.
INSERM Unité 429, Hôpital Necker-Enfants Malades, Paris.
Eliska
E
Holzelova
Cédric
C
Vonarbourg
Marie-Claude
MC
Stolzenberg
Peter D
PD
Arkwright
Françoise
F
Selz
Anne-Marie
AM
Prieur
Stéphane
S
Blanche
Jirina
J
Bartunkova
Etienne
E
Vilmer
Alain
A
Fischer
Françoise
F
Le Deist
Frédéric
F
Rieux-Laucat
D000293:Adolescent; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000145:classification / Q000235:genetics*; D002478:Cells, Cultured; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000145:classification / Q000235:genetics*; D008297:Male; D009030:Mosaicism; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes; D019014:fas Receptor / Q000235:genetics*
D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor