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ABSTRACT The receptor for advanced glycation end products (RAGE) and its proinflammatory S100/calgranulin ligands are enriched in joints of subjects with rheumatoid arthritis (RA) and

amplify the immune/inflammatory response. In a model of inflammatory arthritis, blockade of RAGE in mice immunized and challenged with bovine type II collagen suppressed clinical and

histologic evidence of arthritis, in parallel with diminished levels of TNF-alpha, IL-6, and matrix metalloproteinases (MMP) 3, 9 and 13 in affected tissues. Allelic variation within key

domains of RAGE may influence these proinflammatory mechanisms, thereby predisposing individuals to heightened inflammatory responses. A polymorphism of the RAGE gene within the

ligand-binding domain of the receptor has been identified, consisting of a glycine to serine change at position 82. Cells bearing the RAGE 82S allele displayed enhanced binding and

cytokine/MMP generation following ligation by a prototypic S100/calgranulin compared with cells expressing the RAGE 82G allele. In human subjects, a case-control study demonstrated an

increased prevalence of the 82S allele in patients with RA compared with control subjects. These data suggest that RAGE 82S upregulates the inflammatory response upon engagement of

S100/calgranulins, and, thereby, may contribute to enhanced proinflammatory mechanisms in immune/inflammatory diseases. Access through your institution Buy or subscribe This is a preview of

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18–22 Chapter  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * College of Physicians and Surgeons, Columbia University, New York, NY, USA M A Hofmann, S

Drury, M R Gleason, W Qu, Y Lu, E Lalla, L G Bucciarelli, B Moser, S Itescu, D M Stern & A M Schmidt * Academic Unit of Molecular Vascular Medicine, University of Leeds, Leeds, UK B I

Hudson, M H Stickland & P J Grant * North Shore Long Island Jewish Research Institute, Manhasset, New York, NY, USA S Chitnis, J Monteiro & P K Gregersen * McQuire VA Medical Center

and Medical College of Virginia, Richmond, VA, USA G Moxley Authors * M A Hofmann View author publications You can also search for this author inPubMed Google Scholar * S Drury View author

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inPubMed Google Scholar * A M Schmidt View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to A M Schmidt. ADDITIONAL

INFORMATION This work is supported, in part, by the Surgical Research Fund of the College of Physicians & Surgeons, Columbia University, and by grants from the United States Public

Health Service to DMS and AMS. Support for PKG and the North American Rheumatoid Arthritis Consortium (NARAC) is provided by the National Arthritis Foundation and by the United States Public

Health Service. BIH, MHS and PJG gratefully acknowledge the assistance of Dr Mark S Shearman at Merck, Sharpe and Dohme. BIH is a junior research fellow of the British Heart Foundation

(Junior Research Fellowship FS/2000007). MAH and LGB are postdoctoral research fellows of the Juvenile Diabetes Research Foundation. AMS is a recipient of a Burroughs Wellcome Fund Clinical

Scientist Award in Translational Research. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Hofmann, M., Drury, S., Hudson, B. _et al._ RAGE and

arthritis: the G82S polymorphism amplifies the inflammatory response. _Genes Immun_ 3, 123–135 (2002). https://doi.org/10.1038/sj.gene.6363861 Download citation * Received: 09 January 2002 *

Revised: 27 January 2002 * Accepted: 28 January 2002 * Published: 21 May 2002 * Issue Date: 01 May 2002 * DOI: https://doi.org/10.1038/sj.gene.6363861 SHARE THIS ARTICLE Anyone you share

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Nature SharedIt content-sharing initiative KEYWORDS * receptor * inflammation * polymorphism * S100/calgranulin * joint