Clinical, Immunologic, and Genetic Features of an Autoimmune Lymphoproliferative Syndrome Associated With Abnormal Lymphocyte Apoptosis

Programmed cell death (apoptosis) of activated lymphoan unusual population of CD4CD8 T cells that express the a/b T-cell receptor (TCR). All patients showed defective lymcytes is critical to immune homeostasis. The cell surface protein Fas (CD95) and its ligand play a pivotal role in reguphocyte apoptosis in vitro. Heterozygous mutations of the Fas gene were detected in 8 patients. One ALPS patient lating lymphocyte apoptosis, and defective expression of either Fas or Fas ligand results in marked over accumulation lacked a Fas gene mutation. Healthy relatives with Fas mutations were identified in 7 of 8 ALPS kindreds. These relatives of mature lymphocytes and autoimmune disease in mice. The results of recent studies suggest that defective lymphoalso showed in vitro abnormalities of Fas-mediated lymphocyte apoptosis, but clinical features of ALPS were not prescyte apoptosis caused by mutations of the Fas gene can result in a severe autoimmune lymphoproliferative synent in the vast majority of these individuals. ALPS is a unique clinical syndrome in which in vitro abnormalities of lymphodrome (ALPS) in humans. To define the clinical, genetic, and immunologic spectrum of ALPS, 9 patients and their families cyte apoptosis are associated with abnormal lymphoproliferation and autoimmunity. These findings provide eviwere extensively evaluated with routine clinical studies, lymphocyte phenotyping, genotyping, and in vitro assays dence that apoptosis of activated lymphocytes is an important mechanism for maintaining immunologic homeofor lymphocyte apoptosis. Individual patients were followed up for 3 months to 6 years. ALPS was identified in 9 unrestasis and self-tolerance in humans. Fas gene mutations account for impaired lymphocyte apoptosis in only a subset lated children as manifested by moderate to massive splenomegaly and lymphadenopathy, hypergammaglobulinemia, of patients with ALPS. q 1997 by The American Society of Hematology. autoimmunity, B-cell lymphocytosis, and the expansion of