What does the immunogenetic basis of rheumatoid arthritis teach us about the immunobiology of the disease?

References

• MacGregor AJ, Snieder H, Rigby AS et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum.43(1), 30–37 (2000).
   PubMed Web of Science ®Google Scholar
• Stastny P. Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N. Engl. J. Med.298(16), 869–871 (1978).
   PubMed Web of Science ®Google Scholar
• Hasstedt SJ, Clegg DO, Ingles L, Ward RH. HLA-linked rheumatoid arthritis. Am. J. Hum. Genet.55(4), 738–746 (1994).
   PubMed Web of Science ®Google Scholar
• Michou L, Croiseau P, Petit-Teixeira E et al. the European Consortium on Rheumatoid Arthritis Families. Validation of the reshaped shared epitope HLA-DRB1 classification in rheumatoid arthritis. Arthritis Res. Ther.8(3), R79 (2006).
   Google Scholar
• du Montcel ST, Michou L, Petit-Teixeira E et al. New classification of HLA-DRB1 alleles supports the shared epitope hypothesis of rheumatoid arthritis susceptibility. Arthritis Rheum.52(4), 1063–1068 (2006).
   Google Scholar
• Cope AP, Patel SD, Hall F et al. T cell responses to a human cartilage autoantigen in the context of rheumatoid arthritis-associated and nonassociated HLA-DR4 alleles. Arthritis Rheum.42(7), 1497–1507 (1999).
   PubMed Web of Science ®Google Scholar
• Zanelli E, Krco CJ, David CS. Critical residues on HLA-DRB1*0402 HV3 peptide for HLA-DQ8-restricted immunogenicity: implications for rheumatoid arthritis predisposition. J. Immunol.158(7), 3545–3551 (1997).
   PubMedGoogle Scholar
• Gonzalez-Gay MA, Zanelli E, Khare SD et al. Human leukocyte antigen-DRB1*1502 (DR2Dw12) transgene reduces incidence and severity of arthritis in mice. Hum. Immunol.50(1), 54–60 (1996).
   PubMed Web of Science ®Google Scholar
• Patil NS, Pashine A, Belmares MP et al. Rheumatoid arthritis (RA)-associated HLA-DR alleles form less stable complexes with class II-associated invariant chain peptide than non-RA-associated HLA-DR alleles. J. Immunol.167(12), 7157–7168 (2001).
   PubMedGoogle Scholar
• Salmon M, Akbar AN. Telomere erosion: a new link between HLA DR4 and rheumatoid arthritis? Trends Immunol.25(7), 339–341 (2004).
   PubMedGoogle Scholar
• Akbar AN, Beverley PC, Salmon M. Will telomere erosion lead to a loss of T-cell memory? Nat. Rev. Immunol.4(9), 737–43 (2004).
   PubMed Web of Science ®Google Scholar
• Zendman AJ, Vossenaar ER, van Venrooij WJ. Autoantibodies to citrullinated (poly)peptides: a key diagnostic and prognostic marker for rheumatoid arthritis. Autoimmunity37(4), 295–299 (2004).
   PubMed Web of Science ®Google Scholar
• Nielen MM, van Schaardenburg D, Reesink HW et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum.50(2), 380–386 (2004).
   PubMed Web of Science ®Google Scholar
• Rantapaa-Dahlqvist S, de Jong BA, Berglin E et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum.48(10), 2741–2749 (2003).
   PubMed Web of Science ®Google Scholar
• van Gaalen FA, van Aken J, Huizinga TW et al. Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influences the severity of rheumatoid arthritis. Arthritis Rheum.50(7), 2113–2121 (2004).
   PubMed Web of Science ®Google Scholar
• Kroot EJ, de Jong BA, van Leeuwen MA et al. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum.43(8), 1831–1835 (2000).
   PubMed Web of Science ®Google Scholar
• de Vries RR, Huizinga TW, Toes RE. Redefining the HLA and RA association: to be or not to be anti-CCP positive. J. Autoimmun.25(Suppl.), 21–25 (2005).
   PubMed Web of Science ®Google Scholar
• Hill JA, Southwood S, Sette A, Jevnikar AM, Bell DA, Cairns E. Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J. Immunol.171(2), 538–541 (2003).
   PubMed Web of Science ®Google Scholar
• Huizinga TW, Amos CI, van der Helm-van Mil AH et al. Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins. Arthritis Rheum.52(11), 3433–3438 (2005).
   PubMed Web of Science ®Google Scholar
• Irigoyen P, Lee AT, Wener MH et al. Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: contrasting effects of HLA-DR3 and the shared epitope alleles. Arthritis Rheum.52(12), 3813–8381 (2005).
   PubMed Web of Science ®Google Scholar
• Klareskog L, Stolt P, Lundberg K 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.54(1), 38–46 (2006).
   PubMed Web of Science ®Google Scholar
• Suzuki A, Yamada R, Chang X et al. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat. Genet.34(4), 395–402 (2003).
   PubMed Web of Science ®Google Scholar
• Plenge RM, Padyukov L, Remmers EF et al. Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4. Am. J. Hum. Genet.77(6), 1044–1060 (2005).
   PubMed Web of Science ®Google Scholar
• Chang CH, Flavell RA. Class II transactivator regulates the expression of multiple genes involved in antigen presentation. J. Exp. Med.181(2), 765–767 (1995).
   PubMed Web of Science ®Google Scholar
• Nagarajan UM, Bushey A, Boss JM. Modulation of gene expression by the MHC class II transactivator. J. Immunol.169(9), 5078–5088 (2002).
   PubMed Web of Science ®Google Scholar
• Otten LA, Steimle V, Bontron S, Mach B. Quantitative control of MHC class II expression by the transactivator CIITA. Eur. J. Immunol.28(2), 473–478 (1998).
   PubMedGoogle Scholar
• Swanberg M, Lidman O, Padyukov L et al. MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction. Nat. Genet.37(5), 486–494 (2005).
   PubMed Web of Science ®Google Scholar
• Gregersen PK. Gaining insight into PTPN22 and autoimmunity. Nat. Genet.37(12), 1300–1302 (2005).
   PubMed Web of Science ®Google Scholar
• Carlton VE, Hu X, Chokkalingam AP et al. PTPN22 genetic variation: evidence for multiple variants associated with rheumatoid arthritis. Am. J. Hum. Genet.77(4), 567–581 (2005).
   PubMed Web of Science ®Google Scholar
• Begovich AB, Carlton VE, Honigberg LA et al. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am. J. Hum. Genet.75(2), 330–337 (2004).
   PubMed Web of Science ®Google Scholar
• Viken MK, Amundsen SS, Kvien TK et al. Association analysis of the 1858C>T polymorphism in the PTPN22 gene in juvenile idiopathic arthritis and other autoimmune diseases. Genes Immun.6(3), 271–273 (2005).
   PubMed Web of Science ®Google Scholar
• Seldin MF, Shigeta R, Laiho K et al. Finnish case-control and family studies support PTPN22 R620W polymorphism as a risk factor in rheumatoid arthritis, but suggest only minimal or no effect in juvenile idiopathic arthritis. Genes Immun.6(8), 720–722 (2005).
   PubMed Web of Science ®Google Scholar
• Hinks A, Worthington J, Thomson W. The association of PTPN22 with rheumatoid arthritis and juvenile idiopathic arthritis. Rheumatology (Oxf.)45(4), 365–368 (2006).
   PubMedGoogle Scholar
• Hinks A, Barton A, John S et al. Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene. Arthritis Rheum.52(6), 1694–1699 (2005).
   PubMed Web of Science ®Google Scholar
• Bottini N, Musumeci L, Alonso A et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat. Genet.36(4), 337–338 (2004).
   PubMed Web of Science ®Google Scholar
• Cloutier JF, Veillette A. Association of inhibitory tyrosine protein kinase p50csk with protein tyrosine phosphatase PEP in T cells and other hemopoietic cells. EMBO J.15(18), 4909–4918 (1996).
   PubMed Web of Science ®Google Scholar
• Hasegawa K, Martin F, Huang G, Tumas D, Diehl L, Chan AC. PEST domain-enriched tyrosine phosphatase (PEP) regulation of effector/memory T cells. Science303(5658), 685–689 (2004).
   PubMed Web of Science ®Google Scholar
• Orozco G, Sanchez E, Gonzalez-Gay MA et al. Association of a functional single-nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Rheum.52(1), 219–224 (2005).
   PubMed Web of Science ®Google Scholar
• Lee AT, Li W, Liew A et al. The PTPN22 R620W polymorphism associates with RF positive rheumatoid arthritis in a dose-dependent manner but not with HLA-SE status. Genes Immun.6(2), 129–133 (2005).
   PubMed Web of Science ®Google Scholar
• Burkhardt H, Huffmeier U, Spriewald B et al. Association between protein tyrosine phosphatase 22 variant R620W in conjunction with the HLA-DRB1 shared epitope and humoral autoimmunity to an immunodominant epitope of cartilage-specific type II collagen in early rheumatoid arthritis. Arthritis Rheum.54(1), 82–89 (2006).
   PubMedGoogle Scholar
• van Oene M, Wintle RF, Liu X et al. Association of the lymphoid tyrosine phosphatase R620W variant with rheumatoid arthritis, but not Crohn’s disease, in Canadian populations. Arthritis Rheum.52(7), 1993–1998 (2005).
   PubMedGoogle Scholar
• Simkins HM, Merriman ME, Highton J et al. Association of the PTPN22 locus with rheumatoid arthritis in a New Zealand Caucasian cohort. Arthritis Rheum.52(7), 2222–2225 (2005).
   PubMed Web of Science ®Google Scholar
• Vang T, Congia M, Macis MD et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat. Genet.37(12), 1317–1319 (2005).
   PubMed Web of Science ®Google Scholar
• Wu J, Katrekar A, Honigberg LA et al. Identification of substrates of human protein-tyrosine phosphatase PTPN22.J. Biol. Chem.281(16), 11002–11010 (2006).
   PubMed Web of Science ®Google Scholar
• Lee KM, Chuang E, Griffin M et al. Molecular basis of T cell inactivation by CTLA-4. Science282(5397), 2263–2266 (1998).
   PubMed Web of Science ®Google Scholar
• Phan GQ, Yang JC, Sherry RM et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Natl Acad. Sci. USA100(14), 8372–8377 (2003).
   PubMed Web of Science ®Google Scholar
• Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity3(5), 541–547 (1995).
   PubMed Web of Science ®Google Scholar
• Chambers CA, Sullivan TJ, Allison JP. Lymphoproliferation in CTLA-4-deficient mice is mediated by costimulation-dependent activation of CD4+ T cells. Immunity7(6), 885–895 (1997).
   PubMed Web of Science ®Google Scholar
• Ueda H, Howson JM, Esposito L. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature423(6939), 506–511 (2003).
   PubMed Web of Science ®Google Scholar
• Nistico L, Buzzetti R, Pritchard LE et al. The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry. Hum. Mol. Genet.5(7), 1075–1080 (1996).
   PubMed Web of Science ®Google Scholar
• Atabani SF, Thio CL, Divanovic S et al. Association of CTLA4 polymorphism with regulatory T cell frequency. Eur. J. Immunol.35(7), 2157–2162 (2005).
   PubMed Web of Science ®Google Scholar
• Barton A, Jury F, Eyre S et al. Haplotype analysis in simplex families and novel analytic approaches in a case-control cohort reveal no evidence of association of the CTLA-4 gene with rheumatoid arthritis. Arthritis Rheum.50(3), 748–752 (2004).
   PubMedGoogle Scholar
• Lee YH, Choi SJ, Ji JD, Song GG. No association of polymorphisms of the CTLA-4 exon 1(+49) and promoter(-318) genes with rheumatoid arthritis in the Korean population. Scand. J. Rheumatol.31(5), 266–270 (2002).
   PubMed Web of Science ®Google Scholar
• Lei C, Dongqing Z, Yeqing S et al. Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population. Eur. J. Hum. Genet.13(7), 823–828 (2005).
   PubMedGoogle Scholar
• Han S, Li Y, Mao Y, Xie Y. Meta-analysis of the association of CTLA-4 exon-1 +49A/G polymorphism with rheumatoid arthritis. Hum. Genet.118(1), 123–132 (2005).
   PubMed Web of Science ®Google Scholar
• Kremer JM, Genant HK, Moreland LW et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann. Intern. Med.144(12), 865–876 (2006).
   PubMed Web of Science ®Google Scholar
• Parry RV, Chemnitz JM, Frauwirth KA et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol. Cell Biol.25(21), 9543–9553 (2005).
   PubMed Web of Science ®Google Scholar
• Sheppard KA, Fitz LJ, Lee JM et al. PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3ζ signalosome and downstream signaling to PKCtheta. FEBS Lett.574(1–3), 37–41 (2004).
   PubMed Web of Science ®Google Scholar
• Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity11(2), 141–151 (1999).
   PubMed Web of Science ®Google Scholar
• Nishimura H, Okazaki T, Tanaka Y et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science291(5502), 319–322 (2001).
   PubMed Web of Science ®Google Scholar
• Prokunina L, Castillejo-Lopez C, Oberg F et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat. Genet.32(4), 666–669 (2002).
   PubMed Web of Science ®Google Scholar
• Ferreiros-Vidal I, Gomez-Reino JJ, Barros F et al. Association of PDCD1 with susceptibility to systemic lupus erythematosus: evidence of population-specific effects. Arthritis Rheum50(8), 2590–2597 (2004).
   PubMed Web of Science ®Google Scholar
• Lin SC, Yen JH, Tsai JJ et al. Association of a programmed death 1 gene polymorphism with the development of rheumatoid arthritis, but not systemic lupus erythematosus. Arthritis Rheum.50(3), 770–775 (2004).
   PubMed Web of Science ®Google Scholar
• Prokunina L, Padyukov L, Bennet A et al. Association of the PD-1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope. Arthritis Rheum.50(6), 1770–1773 (2004).
   PubMed Web of Science ®Google Scholar
• Irving BA, Weiss A. The cytoplasmic domain of the T cell receptor ζ chain is sufficient to couple to receptor-associated signal transduction pathways. Cell64(5), 891–901 (1991).
   PubMed Web of Science ®Google Scholar
• D’Oro U, Munitic I, Chacko G, Karpova T, McNally J, Ashwell JD. Regulation of constitutive TCR internalization by the ζ-chain. J. Immunol.169(11), 6269–6278 (2002).
   PubMedGoogle Scholar
• Love PE, Shores EW, Johnson MD et al. T cell development in mice that lack the ζ chain of the T cell antigen receptor complex. Science261(5123), 918–921 (1993).
   PubMedGoogle Scholar
• Shores EW, Tran T, Grinberg A, Sommers CL, Shen H, Love PE. Role of the multiple T cell receptor (TCR)-ζ chain signaling motifs in selection of the T cell repertoire. J. Exp. Med.185(5), 893–900 (1997).
   PubMed Web of Science ®Google Scholar
• Pang M, Setoyama Y, Tsuzaka K et al. Defective expression and tyrosine phosphorylation of the T cell receptor ζ chain in peripheral blood T cells from systemic lupus erythematosus patients. Clin. Exp. Immunol.129(1), 160–168 (2002).
   PubMed Web of Science ®Google Scholar
• Maurice MM, Lankester AC, Bezemer AC et al. Defective TCR-mediated signaling in synovial T cells in rheumatoid arthritis. J. Immunol.159(6), 2973–2978 (1997).
   PubMedGoogle Scholar
• Kono K, Ichihara F, Iizuka H, Sekikawa T, Matsumoto Y. Expression of signal transducing T-cell receptor ζ molecules after adoptive immunotherapy in patients with gastric and colon cancer. Int. J. Cancer78(3), 301–305 (1998).
   PubMed Web of Science ®Google Scholar
• Seitzer U, Kayser K, Hohn H et al. Reduced T-cell receptor CD3∼-chain protein and sustained CD3-ε expression at the site of mycobacterial infection. Immunology104(3), 269–77 (2001).
   PubMed Web of Science ®Google Scholar
• Geertsma MF, van Wengen-Stevenhagen A, van Dam EM et al. Decreased expression of ζ molecules by T lymphocytes is correlated with disease progression in human immunodeficiency virus-infected persons. J. Infect. Dis.180(3), 649–658 (1999).
   PubMedGoogle Scholar
• Cope AP. Studies of T-cell activation in chronic inflammation. Arthritis Res.4 (Suppl. 3), S197–S211 (2002).
   Google Scholar
• Tsuzaka K, Takeuchi T, Onoda N, Pang M, Abe T. Mutations in T cell receptor ζ chain mRNA of peripheral T cells from systemic lupus erythematosus patients. J. Autoimmun.11(5), 381–385 (1998).
   PubMed Web of Science ®Google Scholar
• Wu J, Edberg JC, Gibson AW, Tsao B, Kimberly RP. Single-nucleotide polymorphisms of T cell receptor ζ chain in patients with systemic lupus erythematosus. Arthritis Rheum.42, 2601–2605 (1999).
   PubMed Web of Science ®Google Scholar
• Tsuzaka K, Fukuhara I, Setoyama Y et al. TCR ζ mRNA with an alternatively spliced 3'-untranslated region detected in systemic lupus erythematosus patients leads to the down-regulation of TCR ζ and TCR/CD3 complex. J. Immunol.171(5), 2496–2503 (2003).
   PubMed Web of Science ®Google Scholar
• Chowdhury B, Tsokos CG, Krishnan S. Decreased stability and translation of T cell receptor ζ mRNA with an alternatively spliced 3'-untranslated region contribute to ζ chain down-regulation in patients with systemic lupus erythematosus. J. Biol. Chem280(19), 18959–18966 (2005).
   PubMed Web of Science ®Google Scholar
• Tsuzaka K, Setoyama Y, Yoshimoto K et al. A splice variant of the TCR ζ mRNA lacking exon 7 leads to the down-regulation of TCR ζ, the TCR/CD3 complex, and IL-2 production in systemic lupus erythematosus T cells. J. Immunol.174(6), 3518–3525 (2005).
   PubMed Web of Science ®Google Scholar
• Gorman C, Russell A, Zhang Z, Vyse T, Cope AP. CD3Z polymorphism is associated with reduced expression of the TCR ζ chain: enrichment in patients with severe rheumatoid arthritis. Ann. Rheum. Dis.5, A41 (2006).
   Google Scholar
• Goodnow CC, Sprent J, Fazekas de St Groth B, Vinuesa CG. Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature435(7042), 590–597 (2005).
   PubMed Web of Science ®Google Scholar