[HTML][HTML] Autoimmune Lymphoproliferative Syndrome with Somatic Fas Mutations
E Holzelova, C Vonarbourg… - … England Journal of …, 2004 - Mass Medical Soc
E Holzelova, C Vonarbourg, MC Stolzenberg, PD Arkwright, F Selz, AM Prieur, S Blanche…
New England Journal of Medicine, 2004•Mass Medical SocBackground 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 …
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 …
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.
The New England Journal Of Medicine