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Antinuclear antibodies recognize cellular autoantigens driven by apoptosis
Roxana Ramírez-Sandoval1, Sergio H Sánchez-Rodríguez, David Herrera-van Oostdam
1Department of Molecular Biology, Centro de Biología Experimental, Universidad Autónoma de Zacatecas, Chepinque 306, Col. Lomas de la Soledad, 98040, Zacatecas, Mexico.
Joint Bone Spine
|June 20, 2003
Summary
Apoptosis alters cellular antigens, enhancing the autoantibody response to specific targets like anti-RNP and anti-DNA Topoisomerase I. These changes may contribute to autoimmune diseases by breaking self-tolerance.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Antinuclear autoantibodies (ANAs) are key biomarkers in autoimmune diseases.
- The role of cellular changes, particularly apoptosis, in driving ANA responses is not fully understood.
Purpose of the Study:
- To investigate if apoptosis influences the recognition of cellular antigens by antinuclear autoantibodies.
- To determine how apoptosis-induced modifications affect autoantigen presentation and autoantibody binding.
Main Methods:
- HEp-2 cells were induced into apoptosis using camptothecin.
- Apoptosis was confirmed by monitoring DNA fragmentation, FasL, and Bax expression.
- Autoantigens were analyzed using indirect immunofluorescence, Western blot, and ELISA, comparing reactivity between living and apoptotic cells.
Main Results:
- Apoptosis induced characteristic changes including chromatin fragmentation and blebbing.
- Several autoantigens (U1-RNP, Jo1, DNA Topoisomerase I, CENP-B, NuMA) showed fragmentation and redistribution.
- Antinuclear antibody titers were significantly higher against apoptotic cells compared to living cells.
Conclusions:
- Apoptosis triggers molecular modifications in autoantigens, enhancing the autoantibody response.
- This heightened response to modified autoantigens (e.g., anti-RNP, anti-DNA Topoisomerase I) may play a role in the pathogenesis of autoimmune connective tissue diseases.
- Apoptotic changes are implicated in breaking self-tolerance, contributing to autoimmunity.