OBJECTIVE: A human lymphoproliferative syndrome characterized by a defect of the Fas-mediated apoptosis pathway in the absence of a fas gene mutation (Autoimmune Lymphoproliferative Disease) has recently been described and characterized by autoimmune phenomena. The aim of this study was to investigate the presence of antinuclear and antiphospholipid antibodies and to define their specificity in 5 pediatric patients with this syndrome. METHODS: Antinuclear antibodies were investigated by Western Blot and IIF performed under standard as well as apoptotic conditions. The fine specificity of antiphospholipid antibodies was dissected by an ELISA for anti-beta 2-glycoprotein I, anti-prothrombin, anti-annexin V and anti-protein S antibodies, and by immunostaining on thin layer chromatography plates for antiphospholipid molecule antibodies. RESULTS: This study showed that the autoantibodies found in these patients targeted a broad spectrum of nuclear antigens which undergo redistribution from the nucleus to the cytoplasm and plasma membrane during the course of the apoptotic process. This reactivity does not comprise known specificities such as anti-extractable nuclear antigens or anti-dsDNA. Antiphospholipid antibodies were also found in these sera. A further characterization of the antiphospholipid antibodies showed the presence of a heterogeneous response with antibodies directed to negatively-charged phospholipids and antibodies targeting coagulation-related proteins (beta 2-GPI, prothrombin, annexin V) which are considered relevant antigens in the antiphospholipid syndrome. CONCLUSIONS: These results suggest that lack of tolerance due to a defect of Fas-mediated apoptosis allows the survival of B and T clones involved in the antinuclear and antiphospholipid immune responses.
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