INCREASED SPONTANEOUS IN-VITRO APOPTOSIS IN DOUBLE-NEGATIVE T-CELLS OF HUMANS WITH A FAS APO-1 MUTATION/

We describe a 17 year old patient suffering from Canale-Smith syndrome (CSS) including chronic lymphadenopathy, splenomegaly, hypergammaglob ulinemia and recurrent Coombs positive hemolytic crises. The parents a re not consanguine, all other family members including two brothers ar e healthy, Peripheral blood mononuclear cells of the patient showed an increased rate of CD3 positive, CD4/CD8 double negative T-lymphocytes . In vitro assays showed these cells to have an increased rate of spon taneous apoptosis, Though expression of Fas/Apo-1 (CD95) and Fas-ligan d (FasL) was detected on RNA-and protein level we found Fas/Apo-1 medi ated apoptosis being significantly reduced, Sequencing of the fas/apo- 1 gene proved the patient RT and his father to carry a point mutation at position 804 located in exon 9 (death domain) leading to an amino a cid substitution, For developing of CSS, a fas/apo-1 mutation seems to be necessary but not sufficient, An additional independent mechanism must be involved in the pathogenesis of human lpr-phenotype.