Autoantigens as substrates for apoptotic proteases: implications for the pathogenesis of systemic autoimmune disease (original) (raw)
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- Published: 11 January 1999
Cell Death & Differentiation volume 6, pages 6–12 (1999)Cite this article
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Abstract
Systemic autoimmune diseases are a genetically complex, heterogeneous group of diseases in which the immune system targets a diverse, but highly specific group of intracellular autoantigens. The clustering and marked concentration of these molecules in the surface blebs of apoptotic cells, and their modification by apoptosis-specific proteolytic cleavage and/or phosphorylation at these sites, has focused attention on a unique apoptotic setting as the potential initiating stimulus for systemic autoimmunity. This apoptotic event is likely to (i) occur in a microenvironment containing high concentrations of the targeted antigens, (ii) be pro-immune in nature (e.g. viral infection), and (iii) allow suprathreshold concentrations of antigen with non-tolerized structure (either novel fragments, post-translational modifications, or complexes) to enter the class II processing pathway and initiate a primary immune response. Defective clearance or reduced anti-inflammatory consequences of apoptotic material may be important susceptibility factors in this group of diseases. Once the primary immune response to apoptotic antigens has been initiated, other apoptotic events (occurring in the course of homeostasis or damage) may stimulate the secondary immune response with less stringency, resulting in flares.
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Authors and Affiliations
- Department of Medicine, Johns Hopkins University School of Medicine, USA
Antony Rosen - Department of Pathology, Johns Hopkins University School of Medicine, USA
Antony Rosen - Cell Biology and Anatomy, Johns Hopkins University School of Medicine, USA
Antony Rosen & Livia Casciola-Rosen - Department of Dermatology, Johns Hopkins University School of Medicine, USA
Livia Casciola-Rosen
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- Antony Rosen
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Correspondence toLivia Casciola-Rosen.
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Edited by M. Piacentini
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Rosen, A., Casciola-Rosen, L. Autoantigens as substrates for apoptotic proteases: implications for the pathogenesis of systemic autoimmune disease.Cell Death Differ 6, 6–12 (1999). https://doi.org/10.1038/sj.cdd.4400460
- Received: 22 June 1998
- Revised: 24 September 1998
- Accepted: 28 September 1998
- Published: 11 January 1999
- Issue Date: 01 January 1999
- DOI: https://doi.org/10.1038/sj.cdd.4400460