Clustering of distinct autoimmune diseases associated with functional abnormalities of T cell survival in children.
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.
Pignata
C
C
Department of Paediatrics, 'Federico II' University, Naples, Italy. pignata@unina.it
Alessio
M
M
Ramenghi
U
U
Bonissoni
S
S
Difranco
D
D
Brusco
A
A
Matrecano
E
E
Franzese
A
A
Dianzani
I
I
Dianzani
U
U
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
C064769:N-acetylsphingosine; D019014:fas Receptor; D013110:Sphingosine