Antinuclear antibodies recognize cellular autoantigens driven by apoptosis - 01/01/03
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Résumé |
Objectives. - Present study addresses the issue whether cellular antigens recognised by antinuclear autoantibodies are driven by apoptosis.
Materials and methods. - HEp-2 cells were committed to apoptosis by camptothecin; DNA fragmentation and FasL and Bax expression monitored apoptosis. Autoantigens were probed by indirect immunofluorescence and Western blot with autoantibodies or monoclonals against: DNA, Ro60, La, U1-RNP, CENP-B, DNA Topoisomerase I, Jo-1 and NuMA. A comparison of antinuclear antibody reactivity between living and apoptotic cells was performed by ELISA.
Results. - Apoptotic changes such as chromatin fragmentation, blebs and apoptotic bodies were induced with 20 mM camptothecin. Autoantigens were better detected in apoptotic cells. U1-RNP, Jo1, DNA-Topoisomerase I, CENP-B and NuMA exhibited fragmentation and redistribution as a consequence of apoptosis; in contrast, Ro60 and La ribonucleoproteins did not show proteolysis. Additionally the ELISA titers of antinuclear antibodies were higher in apoptotic cells than in normal cells.
Conclusion. - Apoptosis induces molecular changes in different autoantigens, this modification increases the antigen-driven response of autoantibodies such as anti-RNP, anti-DNA Topoisomerase I, anti-CENP-B and anti-Jo1. Apoptotic changes would contribute to break down the tolerance in autoimmune connective tissue disease.
Mots clés : Antinuclear antibodies ; Apoptosis ; Autoantigens ; Antigen breaking.
Plan
Vol 70 - N° 3
P. 187-194 - juin 2003 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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