Major histocompatibility complex class I-recognizing receptors are disease risk genes in rheumatoid arthritis

Jeng Hsien Yen, Brenda E. Moore, Takako Nakajima, Dirk Scholl, Daniel J Schaid, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticle

288 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1159-1167
Number of pages9
JournalJournal of Experimental Medicine
Volume193
Issue number10
DOIs
StatePublished - May 21 2001

Fingerprint

Major Histocompatibility Complex
Rheumatoid Arthritis
Rheumatoid Vasculitis
HLA Antigens
Vasculitis
KIR Receptors
Genes
Blood Vessels
Histocompatibility Antigens Class I
Histocompatibility Antigens
T-Lymphocytes
Odds Ratio
Ligands
MHC Class I Genes
Population
Clone Cells
Inflammation

Keywords

  • Genetic susceptibility
  • Killer cell immunoglobulin-like receptor
  • Rheumatoid arthritis
  • T cell
  • Vasculitis

ASJC Scopus subject areas

  • Immunology

Cite this

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.

In: Journal of Experimental Medicine, Vol. 193, No. 10, 21.05.2001, p. 1159-1167.

Research output: Contribution to journalArticle

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. In: Journal of Experimental Medicine. 2001 ; Vol. 193, No. 10. pp. 1159-1167.
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