Major Histocompatibility Complex Class I–Recognizing Receptors Are Disease Risk Genes in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a heterogeneous syndrome of which a subset of patients develops vascular inflammation. The genetic determinants that confer risk for rheumatoid vasculitis are not known, but patients with vascular complications are known to have an expansion of CD4+CD28null T cells, a ce...

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Main Authors:	Yen, Jeng-Hsien, Moore, Brenda E., Nakajima, Takako, Scholl, Dirk, Schaid, Daniel J., Weyand, Cornelia M., Goronzy, Jörg J.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2001
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193323/

id	pubmed-2193323
recordtype	oai_dc
spelling	pubmed-21933232008-04-14 Major Histocompatibility Complex Class I–Recognizing Receptors Are Disease Risk Genes in Rheumatoid Arthritis Yen, Jeng-Hsien Moore, Brenda E. Nakajima, Takako Scholl, Dirk Schaid, Daniel J. Weyand, Cornelia M. Goronzy, Jörg J. Original Article Rheumatoid arthritis (RA) is a heterogeneous syndrome of which a subset of patients develops vascular inflammation. The genetic determinants that confer risk for rheumatoid vasculitis are not known, but patients with vascular complications are known to have an expansion of CD4+CD28null T cells, a cell population potentially involved in endothelial damage. CD4+CD28null T cell clones isolated from RA patients with vasculitis were found to express killer cell immunoglobulin–like receptors (KIRs) with the stimulatory KIR2DS2 often present in the absence of opposing inhibitory receptors with related specificities. To test the hypothesis that the KIR2DS2 gene is involved in the development of vasculitis, association studies were performed. The KIR2DS2 gene was significantly enriched among patients with rheumatoid vasculitis compared with normal individuals (odds ratio 5.56, P = 0.001) and patients with RA but no vasculitis (odds ratio 7.96, P = 0.001). Also, the distribution of human histocompatibility leukocyte antigen (HLA)-C, the putative ligand for KIRs, was significantly different in patients with rheumatoid vasculitis in comparison with the control populations. These data suggest that HLA class I–recognizing receptors and HLA class I genes are genetic risk determinants that modulate the pattern of RA expression. Specifically, KIR2DS2 in conjunction with the appropriate HLA-C ligand may have a role in vascular damage by regulating CD4+CD28null T cells. The Rockefeller University Press 2001-05-21 /pmc/articles/PMC2193323/ /pubmed/11369787 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yen, Jeng-Hsien Moore, Brenda E. Nakajima, Takako Scholl, Dirk Schaid, Daniel J. Weyand, Cornelia M. Goronzy, Jörg J.
spellingShingle	Yen, Jeng-Hsien Moore, Brenda E. Nakajima, Takako Scholl, Dirk Schaid, Daniel J. Weyand, Cornelia M. Goronzy, Jörg J. Major Histocompatibility Complex Class I–Recognizing Receptors Are Disease Risk Genes in Rheumatoid Arthritis
author_facet	Yen, Jeng-Hsien Moore, Brenda E. Nakajima, Takako Scholl, Dirk Schaid, Daniel J. Weyand, Cornelia M. Goronzy, Jörg J.
author_sort	Yen, Jeng-Hsien
title	Major Histocompatibility Complex Class I–Recognizing Receptors Are Disease Risk Genes in Rheumatoid Arthritis
title_short	Major Histocompatibility Complex Class I–Recognizing Receptors Are Disease Risk Genes in Rheumatoid Arthritis
title_full	Major Histocompatibility Complex Class I–Recognizing Receptors Are Disease Risk Genes in Rheumatoid Arthritis
title_fullStr	Major Histocompatibility Complex Class I–Recognizing Receptors Are Disease Risk Genes in Rheumatoid Arthritis
title_full_unstemmed	Major Histocompatibility Complex Class I–Recognizing Receptors Are Disease Risk Genes in Rheumatoid Arthritis
title_sort	major histocompatibility complex class i–recognizing receptors are disease risk genes in rheumatoid arthritis
description	Rheumatoid arthritis (RA) is a heterogeneous syndrome of which a subset of patients develops vascular inflammation. The genetic determinants that confer risk for rheumatoid vasculitis are not known, but patients with vascular complications are known to have an expansion of CD4+CD28null T cells, a cell population potentially involved in endothelial damage. CD4+CD28null T cell clones isolated from RA patients with vasculitis were found to express killer cell immunoglobulin–like receptors (KIRs) with the stimulatory KIR2DS2 often present in the absence of opposing inhibitory receptors with related specificities. To test the hypothesis that the KIR2DS2 gene is involved in the development of vasculitis, association studies were performed. The KIR2DS2 gene was significantly enriched among patients with rheumatoid vasculitis compared with normal individuals (odds ratio 5.56, P = 0.001) and patients with RA but no vasculitis (odds ratio 7.96, P = 0.001). Also, the distribution of human histocompatibility leukocyte antigen (HLA)-C, the putative ligand for KIRs, was significantly different in patients with rheumatoid vasculitis in comparison with the control populations. These data suggest that HLA class I–recognizing receptors and HLA class I genes are genetic risk determinants that modulate the pattern of RA expression. Specifically, KIR2DS2 in conjunction with the appropriate HLA-C ligand may have a role in vascular damage by regulating CD4+CD28null T cells.
publisher	The Rockefeller University Press
publishDate	2001
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193323/
_version_	1611431023792357376

Major Histocompatibility Complex Class I–Recognizing Receptors Are Disease Risk Genes in Rheumatoid Arthritis

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