Fas/Apo1 mutations and autoimmune lymphoproliferative syndrome in a patient with type 2 autoimmune hepatitis.
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.
Pensati
L
L
Dipartmento di Pediatria, Università degli Studi di Napoli Federico II, Naples, Italy.
Costanzo
A
A
Ianni
A
A
Accapezzato
D
D
Iorio
R
R
Natoli
G
G
Nisini
R
R
Almerighi
C
C
Balsano
C
C
Vajro
P
P
Vegnente
A
A
Levrero
M
M
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*
D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019014:fas Receptor