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 associa ted with clustering of autoimmune diseases in children, Fas- and C2-ceramid e-induced cell death was evaluated on T cell lines derived from three patie nts affected by clustering of autoimmune disorders. Three patterns were fou nd: patient 3 was resistant to Fas- and C2-ceramide, patient 1 was resistan t to Fas, but sensitive to C2-ceramide, patient 2 was resistant to C2-ceram ide, but sensitive to Fas. By contrast, Fas- and C2-ceramide-induced cell d eath was normal in five children with systemic juvenile rheumatoid arthriti s, five children with insulin-dependent diabetes and 10 age-matched healthy controls. Surface expression of Fas was low in patient 1, but normal in pa tients 2 and 3. Together with normal Fas transcripts, patients 2 and 3 disp layed a transcript 152 bp longer than the normal one retaining intron 5. Ou r data indicate that polyreactive autoimmune syndromes may be associated wi th heterogeneous alteration of the immune response switching-off system.