title: Fas/Apo1 mutations and autoimmune lymphoproliferative syndrome in a patient with type 2 autoimmune hepatitis.
abstract: Inherited mutations of the Fas/Apo1/CD95 gene, a cell-surface receptor involved in cell death signaling and in the control of self-reactivity, characterize the recently identified autoimmune lymphoproliferative syndromes. A patient with type 2 autoimmune hepatitis with the immunologic and genetic features of autoimmune lymphoproliferative syndrome is described. The clinical picture was dominated by liver disease with hepatosplenomegaly and positivity for anti-liver-kidney microsome 1 and anti-liver-cytosol 1 antibodies. A marked increase in CD3+CD4-CD8-T lymphocytes and inherited mutations in Fas alleles that led to the expression of a soluble form of the protein were also found. Fas-mediated apoptosis was deficient in the patient as it was in her mother and her sister, who carried the same allele 2 mutation. This observation links type 2 autoimmune hepatitis, an organ-specific disease, with a genetically determined defect in peripheral tolerance control.
authors.affiliation: Dipartmento di Pediatria, Università degli Studi di Napoli Federico II, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pensati
authors.forename: A
authors.initials: A
authors.lastname: Costanzo
authors.forename: A
authors.initials: A
authors.lastname: Ianni
authors.forename: D
authors.initials: D
authors.lastname: Accapezzato
authors.forename: R
authors.initials: R
authors.lastname: Iorio
authors.forename: G
authors.initials: G
authors.lastname: Natoli
authors.forename: R
authors.initials: R
authors.lastname: Nisini
authors.forename: C
authors.initials: C
authors.lastname: Almerighi
authors.forename: C
authors.initials: C
authors.lastname: Balsano
authors.forename: P
authors.initials: P
authors.lastname: Vajro
authors.forename: A
authors.initials: A
authors.lastname: Vegnente
authors.forename: M
authors.initials: M
authors.lastname: Levrero
mesh_terms: D000483:Alleles; D017209:Apoptosis; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology*; D002675:Child, Preschool; D005260:Female; D006505:Hepatitis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006529:Hepatomegaly; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008111:Liver Function Tests; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D013163:Splenomegaly; D013577:Syndrome; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D019014:fas Receptor / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019014:fas Receptor