2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mortensen, E. S. Articles by Rekvig, O. P. Search for Related Content PubMed PubMed Citation Articles by Mortensen, E. S. Articles by Rekvig, O. P.

Nephritogenic Potential of Anti-DNA Antibodies against Necrotic Nucleosomes

Elin Synnøve Mortensen^*, and Ole Petter Rekvig^,

Departments of ^* Pathology and Biochemistry, Institute of Medical Biology, Medical Faculty, University of Tromsø, and Departments of Pathology and Rheumatology, University Hospital of Northern Norway, Tromsø, Norway

Correspondence: Dr. Ole Petter Rekvig, Department of Biochemistry, Institute of Medical Biology, Medical Faculty, University of Tromsø, N-9037 Tromsø, Norway. Phone: +47-77646203; Fax: +47-77645350; E-mail: olepr{at}fagmed.uit.no

Systemic lupus erythematosus is an inflammatory autoimmune syndrome of unknown cause. Kidney disease is a central and serious complication in this syndrome. Deposition of chromatin-containing immune complexes within glomerular membranes is considered a key event in the pathogenesis of lupus nephritis. One set of autoantibodies that participate in these complexes is directed against components of chromatin, particularly against double-stranded DNA (dsDNA). Matzinger's danger model implicates chromatin fragments as both inducers and glomerular targets for nephritogenic anti-dsDNA and anti-nucleosome antibodies. In context of this model, apoptosis, secondary necrosis, and exposure of chromatin fragments may causally trigger autoimmunity and subsequent lupus nephritis. The exposure of glomerular basement membrane–associated extracellular chromatin depends on an observed acquired downregulation of renal DNase1 transcription and loss of nuclease activity preceding development of severe nephritis; this downregulation would result in reduced fragmentation and clearance of chromatin fragments. These fragments bind glomerular basement membrane structures with high affinity. In addition, exposed chromatin fragments contain structures that stimulate the innate immune system through Toll-like receptors and the adaptive immune system to produce affinity-maturated pathogenic anti-chromatin and anti-dsDNA antibodies that are central to the development of lupus nephritis.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673