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Basic Science for the Clinician 42: Handling the Corpses: Apoptosis, Necrosis, Nucleosomes and (Quite Possibly) the Immunopathogenesis of SLE

Sigal, Leonard H. MD, FACP, FACR

JCR: Journal of Clinical Rheumatology: February 2007 - Volume 13 - Issue 1 - p 44-48
doi: 10.1097/01.rhu.0000256288.09733.22
Basic Science
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Death happens. It is, in essence, part of life. Humans deal with death in a variety of different ways, but often by keeping it at arms’ length. At the cellular level, there are many forms of death, part of the development of organs and tissues (apoptosis) and part of pathologic processes (necrosis). The former, as has been described in an earlier paper in this series, is designed to eliminate the corpse with no evidence that it was ever there. Clearance is usually swift and effective, avoiding inflammation and specific immune interventions or responses. However, there is gathering evidence that autoimmunity leading to systemic lupus erythematosus may be due to ineffective or improper clearance of apoptotic debris, making it proinflammatory and allowing it to become highly immunogenic. This formulation also suggests therapeutic options that have already been demonstrated effective in controlling models of human autoimmune disease. This article reviews some aspects of this theory and some of the molecular biologic features of necrosis, apoptosis, and other forms of cell death.

Alterations in clearance of apoptotic and necrotic cells may be factors influencing health or disease.

From the Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, and the Division of Rheumatology and Connective Tissue Research, Departments of Medicine, Pediatrics, and Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey—Robert Wood Johnson Medical School, New Brunswick, New Jersey.

Reprints: Leonard H. Sigal, MD, Pharmaceutical Research Institute/Bristol-Myers Squibb, J.3100, PO Box 4000, Princeton, NJ 08543-4000. E-mail: leonard.sigal@bms.com

© 2007 Lippincott Williams & Wilkins, Inc.