title: ALPS: an autoimmune human lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis.
abstract: Apoptosis of activated lymphocytes is critical to immune homeostasis. The cell surface receptor Fas is an important mediator of lymphocyte apoptosis; defective Fas expression causes accumulation of lymphocytes and autoimmune disease in mice. Apoptosis defects due to mutations of Fas have also been found in a rare human autoimmune lymphoproliferative syndrome (ALPS). Nine unrelated children with ALPS had lymphadenopathy, autoimmunity and expansion of a normally infrequent population of CD4-CD8-T cells. All nine exhibited impaired lymphocyte apoptosis in vitro, and eight had heterozygous Fas gene mutations. Thus genetic defects in apoptosis pathways are implicated in the pathogenesis of at least one human autoimmune disorder.
authors.affiliation: Laboratory of Gene Transfer, National Center for Human Genome Research Bethesda, MD, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Puck
authors.forename: M C
authors.initials: MC
authors.lastname: Sneller
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000601:surgery; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000601:surgery; D008297:Male; D009154:Mutation; D015398:Signal Transduction; D013156:Splenectomy; D019014:fas Receptor / Q000235:genetics*
chemical_list: D019014:fas Receptor