title: Clustering of distinct autoimmune diseases associated with functional abnormalities of T cell survival in children.
abstract: To ascertain whether alterations of lymphocyte switching off may be associated with clustering of autoimmune diseases in children, Fas- and C2-ceramide-induced cell death was evaluated on T cell lines derived from three patients affected by clustering of autoimmune disorders. Three patterns were found: patient 3 was resistant to Fas- and C2-ceramide, patient 1 was resistant to Fas, but sensitive to C2-ceramide, patient 2 was resistant to C2-ceramide, but sensitive to Fas. By contrast, Fas- and C2-ceramide-induced cell death was normal in five children with systemic juvenile rheumatoid arthritis, five children with insulin-dependent diabetes and 10 age-matched healthy controls. Surface expression of Fas was low in patient 1, but normal in patients 2 and 3. Together with normal Fas transcripts, patients 2 and 3 displayed a transcript 152 bp longer than the normal one retaining intron 5. Our data indicate that polyreactive autoimmune syndromes may be associated with heterogeneous alteration of the immune response switching-off system.
authors.affiliation: Department of Paediatrics, 'Federico II' University, Naples, Italy. pignata@unina.it
authors.forename: C
authors.initials: C
authors.lastname: Pignata
authors.forename: M
authors.initials: M
authors.lastname: Alessio
authors.forename: U
authors.initials: U
authors.lastname: Ramenghi
authors.forename: S
authors.initials: S
authors.lastname: Bonissoni
authors.forename: D
authors.initials: D
authors.lastname: Difranco
authors.forename: A
authors.initials: A
authors.lastname: Brusco
authors.forename: E
authors.initials: E
authors.lastname: Matrecano
authors.forename: A
authors.initials: A
authors.lastname: Franzese
authors.forename: I
authors.initials: I
authors.lastname: Dianzani
authors.forename: U
authors.initials: U
authors.lastname: Dianzani
mesh_terms: D000293:Adolescent; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000145:classification / Q000276:immunology; D008297:Male; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: C064769:N-acetylsphingosine; D019014:fas Receptor; D013110:Sphingosine