Drs. Ling and Holoshitz have a US patent for USPTO 7,074,893.
Research Article
You have full text access to this OnlineOpen article
Activation of nitric oxide signaling by the rheumatoid arthritis shared epitope
Article first published online: 30 OCT 2006
DOI: 10.1002/art.22178
Copyright © 2006 by the American College of Rheumatology
Additional Information
How to Cite
Ling, S., Lai, A., Borschukova, O., Pumpens, P. and Holoshitz, J. (2006), Activation of nitric oxide signaling by the rheumatoid arthritis shared epitope. Arthritis & Rheumatism, 54: 3423–3432. doi: 10.1002/art.22178
Publication History
- Issue published online: 30 OCT 2006
- Article first published online: 30 OCT 2006
- Manuscript Accepted: 26 JUL 2006
- Manuscript Received: 4 APR 2006
Funded by
- NIH. Grant Numbers: AI-47331, AR-46468, AR-20557
- Arthritis Foundation (Innovative Research Grant)
- University of Michigan Biotechnology Development Fund
REFERENCES
- 1, , . The shared epitope hypothesis: an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 1987; 30: 1205–13.Direct Link:
- 2, . Selective binding of self peptides to disease-associated major histocompatibility complex (MHC) molecules: a mechanism for MHC-linked susceptibility to human autoimmune diseases. J Exp Med 1995; 181: 1597–601.
- 3, , , , , , et al. Genetic bias in immune responses to a cassette shared by different microorganisms in patients with rheumatoid arthritis. J Clin Invest 1997; 100: 658–63.
- 4, . The role of polymorphic amino acids of the MHC molecule in the selection of the T cell repertoire. J Immunol 1991; 146: 1093–8.
- 5, , , , . HLA–DRB1 alleles in polymyalgia rheumatica, giant cell arteritis, and rheumatoid arthritis. Arthritis Rheum 1994; 37: 514–20.Direct Link:
- 6, , , , , , et al. Allelic sequence variation in the HLA class II genes and proteins in patients with autoimmune hepatitis. Hepatology 1994; 19: 609–15.Direct Link:
- 7, , , , . The influence of the HLA-DRB1 rheumatoid arthritis shared epitope on the clinical characteristics and radiological outcome of psoriatic arthritis. J Rheumatol 2003; 30: 96–101.
- 8, , , , , . Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia. Int J Cancer 1996; 65: 134–9.Direct Link:
- 9, , , , , , et al. Dog MHC alleles containing the human RA shared epitope confer susceptibility to canine rheumatoid arthritis. Immunogenetics 2001; 53: 669–73.
- 10, , , , , , et al. An HLA-DR1 transgene confers susceptibility to collagen-induced arthritis elicited with human type II collagen. J Exp Med 1997; 185: 1113–22.
- 11, , , , , , et al. T cell epitopes of human myelin oligodendrocyte glycoprotein identified in HLA-DR4 (DRB1*0401) transgenic mice are encephalitogenic and are presented by human B cells. J Immunol 2001; 167: 7119–25.
- 12. Nitric oxide and the immune response. Nat Immunol 2001; 2: 907–16.
- 13, . Nitric oxide and inflammatory joint diseases. Br J Rheumatol 1998; 37: 246–57.
- 14, , . Increased inflammatory activity parallels increased basal nitric oxide production and blunted response to nitric oxide in vivo in rheumatoid arthritis. Ann Rheum Dis 2003; 62: 630–4.
- 15, , , . Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription. Arthritis Rheum 2004; 50: 2995–3003.Direct Link:
- 16, , , . Nitric oxide donors induce large-scale deletion mutations in human lymphoblastoid cells: implications for mutations in T-lymphocytes from arthritis patients. Environ Mol Mutagen 2001; 38: 261–7.Direct Link:
- 17, , , , , , et al. Nitric oxide production in relation to spontaneous B-cell lymphoma and myositis in SJL mice. Cancer Res 1995; 55: 4391–7.
- 18, , , , . Induction of nitric oxide synthase-dependent telomere shortening after functional inhibition of Hsp90 in human tumor cells. Mol Cell Biol 2006; 26: 1452–62.
- 19, , , . HPRT− mutant T cells in the peripheral blood and synovial tissue of patients with rheumatoid arthritis. Arthritis Rheum 1998; 41: 1772–82.Direct Link:
- 20, , , , , , et al. p53 tumor suppressor gene mutations in fibroblast-like synoviocytes from erosion synovium and non-erosion synovium in rheumatoid arthritis. Arthritis Res Ther 2005; 7: R12–8.
- 21, , , , , , et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 2006; 54: 692–701.Direct Link:
- 22, , , , , , et al. Premature telomeric loss in rheumatoid arthritis is genetically determined and involves both myeloid and lymphoid cell lineages. Proc Natl Acad Sci U S A 2003; 100: 13471–6.
- 23, , , , , , et al. Acidic residues in the DR β chain third hypervariable region are required for stimulation of a DR(α, β 1*0402)-restricted T-cell clone. Hum Immunol 1994; 41: 193–200.
- 24, , , , . Dual antigenic recognition by cloned human γδ T cells. J Clin Invest 1992; 89: 308–14.
- 25, , , , , , et al. Expression of perforin and serine esterases by human γ/δ T cells. J Exp Med 1991; 173: 499–502.
- 26, , , , , , et al. Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers. J Clin Invest 2003; 112: 831–42.
- 27, . Hepatitis B core particles as a universal display model: a structure-function basis for development. FEBS Lett 1999; 442: 1–6.
- 28, , , , , , et al. Behavior of a short preS1 epitope on the surface of hepatitis B core particles. Biol Chem 1999; 380: 315–24.
- 29, , , , , , et al. IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice. J Immunol 2003; 170: 270–8.
- 30, , . Nitric-oxide-dependent systemic immunosuppression in animals with progressively growing malignant gliomas. Cell Immunol 2000; 200: 116–27.
- 31. Apoptosis as a therapeutic tool in rheumatoid arthritis. Nat Rev Immunol 2002; 2: 527–35.
- 32
- 33, . γδ T cells: functional plasticity and heterogeneity. Nat Rev Immunol 2002; 2: 336–44.
- 34, , , , , . γδ T cell subsets in patients with arthritis and chronic neutropenia. Ann Rheum Dis 2002; 61: 438–43.
- 35. Activation of γδT cells by mycobacterial antigens in rheumatoid arthritis. Microbes Infect 1999; 1: 197–202.
- 36, , , . Association of tumor necrosis factor microsatellite polymorphisms with HLA–DRB1*04–bearing haplotypes in rheumatoid arthritis patients. Arthritis Rheum 1996; 39: 1109–14.Direct Link:
- 37, , , , , , et al. Efficient detection and immunomagnetic sorting of specific T cells using multimers of MHC class I and peptide with reduced CD8 binding. Nat Med 2000; 6: 707–10.
- 38, , , , . Inhibition of cell cycle progression by a synthetic peptide corresponding to residues 65-79 of an HLA class II sequence: functional similarities but mechanistic differences with the immunosuppressive drug rapamycin. J Immunol 1998; 160: 2215–22.
- 39, , , , , , et al. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 1993; 364: 33–9.
- 40, . Stress management: MHC class I and class I-like molecules as reporters of cellular stress. Immunity 2003; 19: 469–77.
- 41
- 42, , . Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature 2000; 403: 46–53.
- 43, , , , , , et al. Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules. Cell 2003; 112: 607–18.
- 44, , , , , , et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA–DR (shared epitope)– restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 2006; 54: 38–46.Direct Link:
- 45, , , , , , et al. Twin concordance rates for rheumatoid arthritis: results from a nationwide study. Br J Rheumatol 1993; 32: 903–7.
- 46, , , . Methylation-dependent gene silencing induced by interleukin 1β via nitric oxide production. J Exp Med 1999; 190: 1595–604.
- 47. DNA methylation and the association between genetic and epigenetic changes: relation to carcinogenesis. Mutat Res 1997; 375: 1–8.
- 48, , , . Ageing, autoimmunity and arthritis: perturbations of TCR signal transduction pathways with ageing: a biochemical paradigm for the ageing immune system. Arthritis Res Ther 2003; 5: 290–302.
- 49, , , , , . Impact of shared epitope genotype and ethnicity on erosive disease: a meta-analysis of 3,240 rheumatoid arthritis patients. Arthritis Rheum 2004; 50: 400–12.Direct Link:
- 50, , , , , . An independent role of protective HLA class II alleles in rheumatoid arthritis severity and susceptibility. Arthritis Rheum 2005; 52: 2637–44.Direct Link:

1529-0131/asset/olbannerleft.gif?v=1&s=897b81612b4ad6cae003112184adc709261d5f61)
1529-0131/asset/olbannerright.gif?v=1&s=04654f5ea3cbb01656383e0c0d04b16fd0a9a896)
1529-0131/asset/cover.gif?v=1&s=104d5c2bb8ef72deba26790b855af7ab80697a0e)