2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2004121026v1 16/5/1350    most recent 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Reynolds, J. Articles by Pusey, C. D. Search for Related Content PubMed PubMed Citation Articles by Reynolds, J. Articles by Pusey, C. D.

Nasal Administration of Recombinant Rat 3(IV)NC1 Prevents the Development of Experimental Autoimmune Glomerulonephritis in the WKY Rat

John Reynolds^*, Evangelia I. Prodromidi^*, Jason K. Juggapah^*, Danielle S. Abbott^*, Kathryn A. Holthaus, Raghu Kalluri and Charles D. Pusey^*

^* Renal Section, Division of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom; and Center for Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

Address correspondence to: Dr. John Reynolds, Renal Section, Division of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. Phone: 44-020-8383-3152; Fax: 44-020-8383-2062; E-mail: john.reynolds{at}ic.ac.uk

Received for publication December 2, 2004. Accepted for publication February 17, 2005.

Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture’s disease, can be induced in Wistar Kyoto (WKY) rats by immunization with either collagenase-solubilized rat glomerular basement membrane (GBM) or the recombinant NC1 domain of the 3 chain of type IV collagen [3(IV)NC1]. EAG is characterized by circulating and deposited anti–glomerular basement membrane antibodies, focal necrotizing glomerulonephritis with crescent formation, and glomerular infiltration by T cells and macrophages. Previous studies have demonstrated that oral administration of collagenase-solubilized GBM to WKY rats prevented the development of EAG. Nasal administration of specific autoantigens has been reported to be more effective than oral administration in other models of autoimmune disease. The main aim of this study was to investigate further the concept of mucosal tolerance in EAG by examining the effect of nasal administration of recombinant rat 3(IV)NC1. Groups of WKY rats with EAG, induced by immunization with recombinant rat 3(IV)NC1, were given 3(IV)NC1 nasally on 3 consecutive days before immunization, at total cumulative doses of 25, 100, or 250 µg per rat. A dose-dependent effect was observed on the development of EAG. A dose of 25 µg had no effect on disease; 100 µg resulted in a moderate reduction in the severity of nephritis; and 250 µg led to a marked reduction in circulating and deposited antibodies, albuminuria, severity of glomerular abnormalities, and numbers of glomerular CD8+ T cells and macrophages. In addition, there was a reduction in the proliferative response of splenocytes from rats in the high dose group (250 µg) to 3(IV)NC1 in vitro. The results from this study clearly demonstrate for the first time that mucosal tolerance in EAG can be induced by nasal administration of recombinant rat 3(IV)NC1 and that this approach is effective in the prevention of crescentic glomerulonephritis. Further work using new antigen-specific treatment strategies may provide a novel approach to the treatment of patients with anti–glomerular basement membrane disease.

This article has been cited by other articles:

				J. Reynolds, A. Albouainain, M. A. Duda, D. J. Evans, and C. D. Pusey Strain susceptibility to active induction and passive transfer of experimental autoimmune glomerulonephritis in the rat Nephrol. Dial. Transplant., December 1, 2006; 21(12): 3398 - 3408. [Abstract] [Full Text] [PDF]

				L. Chen, T. Hellmark, V. Pedchenko, B. G. Hudson, C. D. Pusey, J. W. Fox, and W. K. Bolton A Nephritogenic Peptide Induces Intermolecular Epitope Spreading on Collagen IV in Experimental Autoimmune Glomerulonephritis J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3076 - 3081. [Abstract] [Full Text] [PDF]

				P. Ronco and H. Debiec Molecular Dissection of Target Antigens and Nephritogenic Antibodies in Membranous Nephropathy: Towards Epitope-Driven Therapies J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1772 - 1774. [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673