Etiology and Pathogenesis of Rheumatoid Arthritis

Kelley's Textbook of Rheumatology: Volume 1-2, Ninth Edition

Volumn 2, Issue , 2012, Pages 1059-1108.e5

  Firestein, Gary S ^a  

^a UC San Diego Health Sciences   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85167757724     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-1-4377-1738-9.00069-4     Document Type: Chapter

References (324)

1. GS Firestein and NJ Zvaifler (2002) How important are T cells in chronic rheumatoid synovitis?: II. T cell-independent mechanisms from beginning to end. Arthritis Rheum 46 298
2. CM Weyand, KC Hicok, DL Conn and JJ Goronzy (1992) The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis. Ann Intern Med 117 801
3. D van der Woude, BA Lie, E Lundström, et al. (2010) Protection against anti-citrullinated protein antibody-positive rheumatoid arthritis is predominantly associated with HLA-DRB1*1301: a meta-analysis of HLA-DRB1 associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in four European populations. Arthritis Rheum 62 1236
4. JM Rak, L Maestroni, N Balandraud, et al. (2009) Transfer of the shared epitope through microchimerism in women with rheumatoid arthritis. Arthritis Rheum 60 73
5. AH van der Helm-van Mil, KN Verpoort, FC Breedveld, et al. (2006) The HLA-DRB1 shared epitope alleles are primarily a risk factor for anti-cyclic citrullinated peptide antibodies and are not an independent risk factor for development of rheumatoid arthritis. Arthritis Rheum 54 1117
6. A Suzuki, R Yamada, X Chang, et al. (2003) Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 34 395
7. AB Begovich, VE Carlton, LA Honigberg, et al. (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75 330
8. EA Stahl, S Raychaudhuri, EF Remmers, et al. (2010) Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 42 508-514
9. H Källberg, B Ding, L Padyukov, et al., EIRA Study Group (2011) Smoking is a major preventable risk factor for rheumatoid arthritis: estimations of risks after various exposures to cigarette smoke. Ann Rheum Dis 70 508
10. JL Nelson, KA Hughes, AG Smith, et al. (1993) Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced amelioration of rheumatoid arthritis. N Engl J Med 329 466
11. P Brennan, J Barrett, M Fiddler, et al. (2000) Maternal-fetal HLA incompatibility and the course of inflammatory arthritis during pregnancy. J Rheumatol 27 2843
12. E Karouzakis, RE Gay, BA Michel, et al. (2009) DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 60 3613
13. CJ Nile, RC Read, M Akil, et al. (2008) Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis. Arthritis Rheum 58 2686
14. Y Nakamachi, S Kawano, M Takenokuchi, et al. (2009) MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheum 60 1294
15. J Stanczyk, C Ospelt, E Karouzakis, et al. (2011) Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation. Arthritis Rheum 63(2), 373-381
16. MF Doran, GR Pond, CS Crowson, et al. (2002) Trends in incidence and mortality in rheumatoid arthritis in Rochester, Minnesota, over a forty-year period. Arthritis Rheum 46 625
17. E Myasoedova, CS Crowson, HM Kremers, et al. (2010) Is the incidence of rheumatoid arthritis rising? Results from Olmsted County, Minnesota, 1955–2007. Arthritis Rheum 62 1572-1582
18. S Abdollahi-Roodsaz, LA Joosten, MI Koenders, et al. (2009) Local interleukin-1-driven joint pathology is dependent on toll-like receptor 4 activation. Am J Pathol 175 2004
19. JY Choe, B Crain, SR Wu and M Corr (2003) Interleukin 1 receptor dependence of serum transferred arthritis can be circumvented by toll-like receptor 4 signaling. J Exp Med 197 537
20. MM Nielen, D van Schaardenburg, HW Reesink, et al. (2004) Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 50 38
21. KP Liang, H Maradit Kremers, CS Crowson, et al. (2009) Autoantibodies and the risk of cardiovascular events. J Rheumatol 36(11), 2462-2468
22. AJ Rawson, JL Hollander, FP Quismorio and NM Abelson (1969) Experimental arthritis in man and rabbit dependent upon serum anti-immunoglobulin factors. Ann N Y Acad Sci 168 188
23. SK Lee, SL Bridges Jr, WJ Koopman and HW Schroeder Jr (1992) The immunoglobulin kappa light chain repertoire expressed in the synovium of a patient with rheumatoid arthritis. Arthritis Rheum 35 905
24. L De Rycke, AP Nicholas, T Cantaert, et al. (2005) Synovial intracellular citrullinated proteins colocalizing with peptidyl arginine deiminase as pathophysiologically relevant antigenic determinants of rheumatoid arthritis-specific humoral autoimmunity. Arthritis Rheum 52 2323
25. ER Vossenaar, TJ Smeets, MC Kraan, et al. (2004) The presence of citrullinated proteins is not specific for rheumatoid synovial tissue. Arthritis Rheum 50 3485
26. L Damjanovska, MM Thabet, EW Levarth, et al. (2010) Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis. Ann Rheum Dis 69 730
27. GJ Pruijn, A Wiik and WJ van Venrooij (2010) The use of citrullinated peptides and proteins for the diagnosis of rheumatoid arthritis. Arthritis Res Ther 12 203
28. LA van de Stadt, AR van der Horst, MH de Koning, et al. (2011) The extent of the anti-citrullinated protein antibody repertoire is associated with arthritis development in patients with seropositive arthralgia. Ann Rheum Dis 70 128
29. KD Deane, CI O'Donnell, W Hueber, et al. (2010) The number of elevated cytokines and chemokines in preclinical seropositive rheumatoid arthritis predicts time to diagnosis in an age-dependent manner. Arthritis Rheum 62 3161
30. FJ López-Longo, D Oliver-Miñarro, I de la Torre, et al. (2009) Association between anti-cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis. Arthritis Rheum 61 419
31. EM Haisma, EW Levarht, D van der Woude, et al. (2009) Anti-cyclic citrullinated peptide antibodies from rheumatoid arthritis patients activate complement via both the classical and alternative pathways. Arthritis Rheum 60 1923
32. JA Hill, DA Bell, W Brintnell, et al. (2008) Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice. J Exp Med 205 967
33. J Bäcklund, S Carlsen, T Höger, et al. (2002) Predominant selection of T cells specific for the glycosylated collagen type II epitope (263–270) in humanized transgenic mice and in rheumatoid arthritis. Proc Natl Acad Sci U S A 10 1073
34. V Kouskoff, AS Korganow, V Duchatelle, et al. (1996) Organ-specific disease provoked by systemic autoimmunity. Cell 87 811
35. L Mandik-Nayak and PM Allen (2005) Initiation of an autoimmune response: insights from a transgenic model of rheumatoid arthritis. Immunol Res 32 5
36. V Nell-Duxneuner, K Machold, T Stamm, et al. (2010) Autoantibody profiling in patients with very early rheumatoid arthritis: a follow-up study. Ann Rheum Dis 69 169
37. VP Nell, KP Machold, TA Stamm, et al. (2005) Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis 64 1731
38. M Corr and NJ Zvaifler (2002) Mesenchymal precursor cells. Ann Rheum Dis 61 3
39. PA Revell, PI Mapp, PA Lalor and PA Hall (1987) Proliferative activity of cells in the synovium as demonstrated by a monoclonal antibody, Ki67. Rheumatol Int 7 183
40. X Valencia, JM Higgins, HP Kiener, et al. (2004) Cadherin-11 provides specific cellular adhesion between fibroblast-like synoviocytes. J Exp Med 200 1673
41. HP Kiener, GF Watts, Y Cui, et al. (2010) Synovial fibroblasts self-direct multicellular lining architecture and synthetic function in three-dimensional organ culture. Arthritis Rheum 62 742
42. TC van der Pouw Kraan, FA van Gaalen, PV Kasperkovitz, et al. (2003) Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues. Arthritis Rheum 48 2132
43. R Lafyatis, EF Remmers, AB Roberts, et al. (1989) Anchorage-independent growth of synoviocytes from arthritis and normal joints: stimulation by exogenous platelet-derived growth factor and inhibition by transforming growth factor-beta and retinoids. J Clin Invest 83 1267
44. F Imamura, H Aono, T Hasunuma, et al. (1998) Monoclonal expansion of synoviocytes in rheumatoid arthritis. Arthritis Rheum 41 1979
45. L Muller-Ladner, J Kriegsmann, BN Franklin, et al. (1996) Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice. Am J Pathol 149 1607
46. JD Cañete, B Santiago, T Cantaert, et al. (2007) Ectopic lymphoid neogenesis in psoriatic arthritis. Ann Rheum Dis 66 720
47. T Cantaert, J Kolln, T Timmer, et al. (2008) B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis. J Immunol 181 785
48. A Manzo, S Paoletti, M Carulli, et al. (2005) Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis. Eur J Immunol 35 1347
49. YM Kang, X Zhang, UG Wagner, et al. (2002) CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synovitis. J Exp Med 195 1325
50. WJ Kim, YJ Kang, EM Koh, et al. (2005) LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro-inflammatory cytokines and MMP-9 in macrophages. Immunology 114 272
51. KJ Warrington, S Takemura, JJ Goronzy and CM Wayland (2001) CD4+, CD28− T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems. Arthritis Rheum 44 13
52. K Hirota, H Yoshitomi, M Hashimoto, et al. (2007) Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med 204 2803
53. FM Brennan, AL Hayes, CJ Ciesielski, et al. (2002) Evidence that rheumatoid arthritis synovial T cells are similar to cytokine-activated T cells: involvement of phosphatidylinositol 3-kinase and nuclear factor kappaB pathways in tumor necrosis factor alpha production in rheumatoid arthritis. Arthritis Rheum 46 31
54. TM Seyler, YW Park, S Takemura, et al. (2005) BLyS and APRIL in rheumatoid arthritis. J Clin Invest 115 3083
55. BE Clausen, SL Bridges Jr, JC Lavelle, et al. (1998) Clonally-related immunoglobulin VH domains and nonrandom use of DH gene segments in rheumatoid arthritis synovium. Mol Med 4 240
56. A Kavanaugh, S Rosengren, SJ Lee, et al. (2008) Assessment of rituximab's immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results. Ann Rheum Dis 67 402
57. F Humby, M Bombardieri, A Manzo, et al. (2009) Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium. PLoS Med 6 e1
58. DM Lee, DS Friend, MF Gurish, et al. (2002) Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 297 1689
59. AJ Hueber, DL Asquith, AM Miller, et al. (2010) Mast cells express IL-17A in rheumatoid arthritis synovium. J Immunol 184 3336
60. N Dalbeth, R Gundle, RJ Davies, et al. (2004) CD56bright NK cells are enriched at inflammatory sites and can engage with monocytes in a reciprocal program of activation. J Immunol 173 6418
61. L Marinova-Mutafchieva, RO Williams, K Funa, et al. (2002) Inflammation is preceded by tumor necrosis factor-dependent infiltration of mesenchymal cells in experimental arthritis. Arthritis Rheum 46 507
62. DL Boyle, TL Jones, D Hammaker, et al. (2006) Regulation of peripheral inflammation by spinal p38 MAP kinase in rats. PLoS Med 3(9), e338
63. Z Han, DL Boyle, AM Manning and GS Firestein (1998) AP-1 and NF-κB regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimmunity 28 197
64. A Fukushima, DL Boyle, M Corr and GS Firestein (2010) Kinetic analysis of synovial signalling and gene expression in animal models of arthritis. Ann Rheum Dis 69 918
65. H Jonsson, P Allen and SL Peng (2005) Inflammatory arthritis requires Foxo3a to prevent Fas ligand-induced neutrophil apoptosis. Nat Med 11 666
66. GS Firestein, AE Berger, DE Tracey, et al. (1992) IL-1 receptor antagonist protein production and gene expression in rheumatoid arthritis and osteoarthritis synovium. J Immunol 149 1054
67. MM Maurice, H Nakamura, EA van der Voort, et al. (1997) Evidence for the role of an altered redox state in hyporesponsiveness of synovial T cells in rheumatoid arthritis. Immunology 158 1458
68. CE Vergunst, DM Gerlag, H Dinant, et al. (2007) Blocking the receptor for C5a in patients with rheumatoid arthritis does not reduce synovial inflammation. Rheumatology (Oxford) 46 1773
69. I Siegle, T Klein, JT Backman, et al. (1998) Expression of cyclooxygenase 1 and cyclooxygenase 2 in human synovial tissue: differential elevation of cyclooxygenase 2 in inflammatory joint diseases. Arthritis Rheum 41 122
70. C Yao, D Sakata, Y Esaki, et al. (2009) Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nat Med 15 633
71. GS Firestein, WD Xu, K Townsend, et al. (1988) Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. J Exp Med 168 1573
72. K Raza, F Falciani, SJ Curnow, et al. (2005) Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther 7 R784
73. M Chabaud, JM Durand, N Buchs, et al. (1999) Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 43 963
74. MR Ehrenstein, JG Evans, A Singh, S Moore, et al. (2004) Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Med 200 277
75. CR Ruprecht, M Gattorno, F Ferlito, et al. (2005) Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia. J Exp Med 201 1793
76. ME Morgan, R Flierman, LM van Duivenvoorde, et al. (2005) Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells. Arthritis Rheum 52 2212
77. P Chomarat, J Banchereau and P Miossec (1995) Differential effects of interleukins 10 and 4 on the production of interleukin-6 by blood and synovium monocytes in rheumatoid arthritis. Arthritis Rheum 38 1046
78. W Hueber, DD Patel, T Dryja, et al. (2010) Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2 52ra72
79. IB McInnes, BP Leung, RD Sturrock, et al. (1997) Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis. Nat Med 3 189-195
80. GS Firestein, JM Alvaro-Gracia and R Maki (1990) Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol 144 3347
81. MC Genovese, S Cohen, L Moreland, et al. (2004) Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum 50 1412
82. D Xu, HR Jiang, P Kewin, et al. (2008) IL-33 exacerbates antigen-induced arthritis by activating mast cells. Proc Natl Acad Sci U S A 105 10913
83. S Georgopoulos, D Plows and G Kollias (1996) Transmembrane TNF is sufficient to induce localized tissue toxicity and chronic inflammatory arthritis in transgenic mice. J Inflamm 46 86
84. PE Lipsky, DM van der Heijde, EW St Clair, et al. (2000) Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. N Engl J Med 343 1594
85. N Nishimoto, K Yoshizaki, N Miyasaka, et al. (2004) Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 50 1761
86. LA Joosten, MG Netea, SH Kim, et al. (2006) IL-32, a proinflammatory cytokine in rheumatoid arthritis. Proc Natl Acad Sci U S A 103 3298
87. WD Xu, GS Firestein, R Taetle, et al. (1989) Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions. J Clin Invest 83 876
88. AE Koch, SL Kunkel, JC Burrows, et al. (1991) Synovial tissue macrophage as a source of the chemotactic cytokine IL-8. J Immunol 147 2187
89. C Schmutz, A Hulme, A Burman, et al. (2005) Chemokine receptors in the rheumatoid synovium: upregulation of CXCR5. Arthritis Res Ther 7 R217
90. T Nanki, Y Urasaki, T Imai, et al. (2004) Inhibition of fractalkine ameliorates murine collagen-induced arthritis. J Immunol 173 7010
91. JJ Haringman, TJ Smeets, P Reinders-Blankert and PP Tak (2006) Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis. Ann Rheum Dis 65 294
92. M Camps, T Ruckle, H Ji, et al. (2005) Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med 11 936
93. PP Tak, DM Gerlag, KB Aupperle, et al. (2001) Inhibitor of nuclear factor kappaB kinase beta is a key regulator of synovial inflammation. Arthritis Rheum 44 1897
94. Z Han, DL Boyle, AM Manning and GS Firestein (1998) AP-1 and NF-kB regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimmunity 28 197
95. Z Han, DL Boyle, L Chang, et al. (2001) c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 108 73
96. TC van der Pouw Kraan, FA van Gaalen, PV Kasperkovitz, et al. (2003) Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues. Arthritis Rheum 48 2132
97. ME Weinblatt, A Kavanaugh, R Burgos-Vargas, et al. (2008) Treatment of rheumatoid arthritis with a Syk kinase inhibitor: a twelve-week, randomized, placebo-controlled trial. Arthritis Rheum 58 3309
98. T Pap, JK Franz, KM Hummel, et al. (2000) Activation of synovial fibroblasts in rheumatoid arthritis: lack of expression of the tumour suppressor PTEN at sites of invasive growth and destruction. Arthritis Res 2 59
99. JC Scatizzi, J Hutcheson, RM Pope, et al. (2010) Bim-Bcl-2 homology 3 mimetic therapy is effective at suppressing inflammatory arthritis through the activation of myeloid cell apoptosis. Arthritis Rheum 62 441
100. Y Yamanishi, DL Boyle, MJ Pinkoski, et al. (2002) Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis. Am J Pathol 160 123
101. GS Firestein, F Echeverri, M Yeo, et al. (1997) Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. Proc Natl Acad Sci U S A 94 10895
102. E Izquierdo, JD Cañete, R Celis, et al. (2009) Immature blood vessels in rheumatoid synovium are selectively depleted in response to anti-TNF therapy. PLoS One 4 e8131
103. T Cramer, Y Yamanishi, BE Clausen, et al. (2003) HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell 112 645
104. AE Koch, MM Halloran, CJ Haskell, et al. (1995) Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature 376 517
105. DJ Peacock, ML Banquerigo and E Brahn (1992) Angiogenesis inhibition suppresses collagen arthritis. J Exp Med 175 1135
106. CM Storgard, DG Stupack, A Jonczyk, et al. (1998) Decreased angiogenesis and arthritis in rabbits treated with an αvβ3 antagonist. J Clin Invest 103 47
107. TB Issekutz and AC Issekutz (1991) T lymphocyte migration to arthritic joints and dermal inflammation in the rat: differing migration patterns and the involvement of VLA-4. Clin Immunol Immunopathol 61 436
108. DM Lee, HP Kiener, SK Agarwal, et al. (2007) Cadherin-11 in synovial lining formation and pathology in arthritis. Science 315 1006
109. GC Wolfe, KL MacNaul, FF Buechel, et al. (1993) Differential in vivo expression of collagenase messenger RNA in synovium and cartilage: quantitative comparison with stromelysin messenger RNA levels in human rheumatoid arthritis and osteoarthritis patients and in two animal models of acute inflammatory arthritis. Arthritis Rheum 36 1540
110. JS Mudgett, NI Hutchinson, NA Chartrain, et al. (1998) Susceptibility of stromelysin 1–deficient mice to collagen-induced arthritis and cartilage destruction. Arthritis Rheum 41 110
111. WS Hou, W Li, G Keyszer, et al. (2002) Comparison of cathepsins K and S expression within the rheumatoid and osteoarthritic synovium. Arthritis Rheum 46 663
112. L Svelander, H Erlandsson-Harris, L Astner, et al. (2009) Inhibition of cathepsin K reduces bone erosion, cartilage degradation and inflammation evoked by collagen-induced arthritis in mice. Eur J Pharmacol 613 155
113. MW Lark, EK Bayne, J Flanagan, et al. (1997) Aggrecan degradation in human cartilage: evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints. J Clin Invest 100 93
114. Y Yamanishi, DL Boyle, M Clark, et al. (2002) Expression and regulation of aggrecanase in arthritis: the role of TGF-beta. J Immunol 168 1405
115. H Stanton, FM Rogerson, CJ East, et al. (2005) ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature 434 648
116. YY Kong, U Feige, I Sarosi, et al. (1999) Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402 304-309
117. S Kotake, N Udagawa, M Hakoda, et al. (2001) Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients. Arthritis Rheum 44 1003
118. D Diarra, M Stolina, K Polzer, et al. (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13 156
119. M Sen, M Chamorro, J Reifert, et al. (2001) Blockade of Wnt-5A/frizzled 5 signaling inhibits rheumatoid synoviocyte activation. Arthritis Rheum 44 772
120. GS Firestein and NJ Zvaifler (2002) How important are T cells in chronic rheumatoid synovitis?: II. T cell-independent mechanisms from beginning to end. Arthritis Rheum 46 298
121. CM Weyand, KC Hicok, DL Conn and JJ Goronzy (1992) The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis. Ann Intern Med 117 801
122. D van der Woude, BA Lie, E Lundström, et al. (2010) Protection against anti-citrullinated protein antibody-positive rheumatoid arthritis is predominantly associated with HLA-DRB1*1301: a meta-analysis of HLA-DRB1 associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in four European populations. Arthritis Rheum 62 1236
123. JM Rak, L Maestroni, N Balandraud, et al. (2009) Transfer of the shared epitope through microchimerism in women with rheumatoid arthritis. Arthritis Rheum 60 73
124. AH van der Helm-van Mil, KN Verpoort, FC Breedveld, et al. (2006) The HLA-DRB1 shared epitope alleles are primarily a risk factor for anti-cyclic citrullinated peptide antibodies and are not an independent risk factor for development of rheumatoid arthritis. Arthritis Rheum 54 1117
125. CP Kang, KW Lee, DH Yoo, et al. (2005) The influence of a polymorphism at position -857 of the tumour necrosis factor alpha gene on clinical response to etanercept therapy in rheumatoid arthritis. Rheumatology (Oxford) 44 547
126. A Suzuki, R Yamada, X Chang, et al. (2003) Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 34 395
127. AB Begovich, VE Carlton, LA Honigberg, et al. (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75 330
128. EA Stahl, S Raychaudhuri, EF Remmers, et al. (2010) Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 42 508-514
129. SP Linn-Rasker, AH van der Helm-van Mil, FA van Gaalen, et al. (2006) Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis 65 366
130. MF Doran, CS Crowson, WM O’Fallon and SE Gabriel (2004) The effect of oral contraceptives and estrogen replacement therapy on the risk of rheumatoid arthritis: a population based study. J Rheumatol 31 207
131. E Lundström, H Källberg, L Alfredsson, et al. (2009) Gene-environment interaction between the DRB1 shared epitope and smoking in the risk of anti-citrullinated protein antibody-positive rheumatoid arthritis: all alleles are important. Arthritis Rheum 60 1597
132. H Källberg, B Ding, L Padyukov, et al., EIRA Study Group (2011) Smoking is a major preventable risk factor for rheumatoid arthritis: estimations of risks after various exposures to cigarette smoke. Ann Rheum Dis 70 508
133. TJ Lang (2004) Estrogen as an immunomodulator. Clin Immunol 113 224
134. Z Yan, NC Lambert, M Ostensen, et al. (2006) Prospective study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis. Arthritis Rheum 54 2069
135. JL Nelson, KA Hughes, AG Smith, et al. (1993) Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced amelioration of rheumatoid arthritis. N Engl J Med 329 466
136. P Brennan, J Barrett, M Fiddler, et al. (2000) Maternal-fetal HLA incompatibility and the course of inflammatory arthritis during pregnancy. J Rheumatol 27 2843
137. E Karouzakis, RE Gay, BA Michel, et al. (2009) DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 60 3613
138. CJ Nile, RC Read, M Akil, et al. (2008) Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis. Arthritis Rheum 58 2686
139. Y Nakamachi, S Kawano, M Takenokuchi, et al. (2009) MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheum 60 1294
140. J Stanczyk, C Ospelt, E Karouzakis, et al. (2011) Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation. Arthritis Rheum 63(2), 373-381
141. MF Doran, GR Pond, CS Crowson, et al. (2002) Trends in incidence and mortality in rheumatoid arthritis in Rochester, Minnesota, over a forty-year period. Arthritis Rheum 46 625
142. E Myasoedova, CS Crowson, HM Kremers, et al. (2010) Is the incidence of rheumatoid arthritis rising? Results from Olmsted County, Minnesota, 1955–2007. Arthritis Rheum 62 1572-1582
143. S Abdollahi-Roodsaz, LA Joosten, MI Koenders, et al. (2009) Local interleukin-1-driven joint pathology is dependent on toll-like receptor 4 activation. Am J Pathol 175 2004
144. JY Choe, B Crain, SR Wu and M Corr (2003) Interleukin 1 receptor dependence of serum transferred arthritis can be circumvented by toll-like receptor 4 signaling. J Exp Med 197 537
145. NB Ray, DR Nieva, EA Seftor, et al. (2001) Induction of an invasive phenotype by human parvovirus B19 in normal human synovial fibroblasts. Arthritis Rheum 44 1582
146. MM Nielen, D van Schaardenburg, HW Reesink, et al. (2004) Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 50 38
147. KP Liang, H Maradit Kremers, CS Crowson, et al. (2009) Autoantibodies and the risk of cardiovascular events. J Rheumatol 36(11), 2462-2468
148. AJ Rawson, JL Hollander, FP Quismorio and NM Abelson (1969) Experimental arthritis in man and rabbit dependent upon serum anti-immunoglobulin factors. Ann N Y Acad Sci 168 188
149. JP Bouvet, WJ Xin and J Pillot (1987) Restricted heterogeneity of polyclonal rheumatoid factor. Arthritis Rheum 30 998
150. SK Lee, SL Bridges Jr, WJ Koopman and HW Schroeder Jr (1992) The immunoglobulin kappa light chain repertoire expressed in the synovium of a patient with rheumatoid arthritis. Arthritis Rheum 35 905
151. L De Rycke, AP Nicholas, T Cantaert, et al. (2005) Synovial intracellular citrullinated proteins colocalizing with peptidyl arginine deiminase as pathophysiologically relevant antigenic determinants of rheumatoid arthritis-specific humoral autoimmunity. Arthritis Rheum 52 2323
152. ER Vossenaar, TJ Smeets, MC Kraan, et al. (2004) The presence of citrullinated proteins is not specific for rheumatoid synovial tissue. Arthritis Rheum 50 3485
153. C Anzilotti, G Merlini, F Pratesi, et al. (2006) Antibodies to viral citrullinated peptide in rheumatoid arthritis. J Rheumatol 33 647
154. L Damjanovska, MM Thabet, EW Levarth, et al. (2010) Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis. Ann Rheum Dis 69 730
155. GJ Pruijn, A Wiik and WJ van Venrooij (2010) The use of citrullinated peptides and proteins for the diagnosis of rheumatoid arthritis. Arthritis Res Ther 12 203
156. LA van de Stadt, AR van der Horst, MH de Koning, et al. (2011) The extent of the anti-citrullinated protein antibody repertoire is associated with arthritis development in patients with seropositive arthralgia. Ann Rheum Dis 70 128
157. KD Deane, CI O'Donnell, W Hueber, et al. (2010) The number of elevated cytokines and chemokines in preclinical seropositive rheumatoid arthritis predicts time to diagnosis in an age-dependent manner. Arthritis Rheum 62 3161
158. HS El-Gabalawy, DB Robinson, D Hart, et al. (2009) Immunogenetic risks of anti-cyclical citrullinated peptide antibodies in a North American Native population with rheumatoid arthritis and their first-degree relatives. J Rheumatol 6 1130
159. FJ López-Longo, D Oliver-Miñarro, I de la Torre, et al. (2009) Association between anti-cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis. Arthritis Rheum 61 419
160. EM Haisma, EW Levarht, D van der Woude, et al. (2009) Anti-cyclic citrullinated peptide antibodies from rheumatoid arthritis patients activate complement via both the classical and alternative pathways. Arthritis Rheum 60 1923
161. AJ Schuerwegh, A Ioan-Facsinay, AL Dorjée, et al. (2010) Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis. Proc Natl Acad Sci U S A 107 2586
162. KA Kuhn, L Kulik, B Tomooka, et al. (2006) Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis. J Clin Invest 116 961
163. JA Hill, DA Bell, W Brintnell, et al. (2008) Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice. J Exp Med 205 967
164. H Burkhardt, B Sehnert, R Bockermann, et al. (2005) Humoral immune response to citrullinated collagen type II determinants in early rheumatoid arthritis. Eur J Immunol 35 1643
165. WC Watson, MA Cremer, PH Wooley and AS Townes (1986) Assessment of the potential pathogenicity of type II collagen autoantibodies in patients with rheumatoid arthritis. Arthritis Rheum 29 1316
166. J Bäcklund, S Carlsen, T Höger, et al. (2002) Predominant selection of T cells specific for the glycosylated collagen type II epitope (263–270) in humanized transgenic mice and in rheumatoid arthritis. Proc Natl Acad Sci U S A 10 1073
167. T Sekine, K Masuko-Hongo, T Matsui, et al. (2001) Recognition of YKL-39, a human cartilage related protein, as a target antigen in patients with rheumatoid arthritis. Ann Rheum Dis 60 49
168. G Steiner and J Smolen (2002) Autoantibodies in rheumatoid arthritis and their clinical significance. Arthritis Res 4 S1
169. V Kouskoff, AS Korganow, V Duchatelle, et al. (1996) Organ-specific disease provoked by systemic autoimmunity. Cell 87 811
170. L Mandik-Nayak and PM Allen (2005) Initiation of an autoimmune response: insights from a transgenic model of rheumatoid arthritis. Immunol Res 32 5
171. S Hayer, M Tohidast-Akrad, S Haralambous, et al. (2005) Aberrant expression of the autoantigen heterogeneous nuclear ribonucleoprotein-A2 (RA33) and spontaneous formation of rheumatoid arthritis-associated anti-RA33 autoantibodies in TNF-alpha transgenic mice. J Immunol 175 8327
172. V Nell-Duxneuner, K Machold, T Stamm, et al. (2010) Autoantibody profiling in patients with very early rheumatoid arthritis: a follow-up study. Ann Rheum Dis 69 169
173. VP Nell, KP Machold, TA Stamm, et al. (2005) Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis 64 1731
174. M Corr and NJ Zvaifler (2002) Mesenchymal precursor cells. Ann Rheum Dis 61 3
175. PA Revell, PI Mapp, PA Lalor and PA Hall (1987) Proliferative activity of cells in the synovium as demonstrated by a monoclonal antibody, Ki67. Rheumatol Int 7 183
176. X Valencia, JM Higgins, HP Kiener, et al. (2004) Cadherin-11 provides specific cellular adhesion between fibroblast-like synoviocytes. J Exp Med 200 1673
177. HP Kiener, GF Watts, Y Cui, et al. (2010) Synovial fibroblasts self-direct multicellular lining architecture and synthetic function in three-dimensional organ culture. Arthritis Rheum 62 742
178. TC van der Pouw Kraan, FA van Gaalen, PV Kasperkovitz, et al. (2003) Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues. Arthritis Rheum 48 2132
179. R Lafyatis, EF Remmers, AB Roberts, et al. (1989) Anchorage-independent growth of synoviocytes from arthritis and normal joints: stimulation by exogenous platelet-derived growth factor and inhibition by transforming growth factor-beta and retinoids. J Clin Invest 83 1267
180. F Imamura, H Aono, T Hasunuma, et al. (1998) Monoclonal expansion of synoviocytes in rheumatoid arthritis. Arthritis Rheum 41 1979
181. L Muller-Ladner, J Kriegsmann, BN Franklin, et al. (1996) Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice. Am J Pathol 149 1607
182. S Lefèvre, A Knedla, C Tennie, et al. (2009) Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med 15 1414
183. JD Cañete, B Santiago, T Cantaert, et al. (2007) Ectopic lymphoid neogenesis in psoriatic arthritis. Ann Rheum Dis 66 720
184. T Cantaert, J Kolln, T Timmer, et al. (2008) B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis. J Immunol 181 785
185. A Manzo, S Paoletti, M Carulli, et al. (2005) Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis. Eur J Immunol 35 1347
186. T Tsubaki, S Takegawa, H Hanamoto, et al. (2005) Accumulation of plasma cells expressing CXCR3 in the synovial sublining regions of early rheumatoid arthritis in association with production of Mig/CXCL9 by synovial fibroblasts. Clin Exp Immunol 141 363
187. YM Kang, X Zhang, UG Wagner, et al. (2002) CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synovitis. J Exp Med 195 1325
188. WJ Kim, YJ Kang, EM Koh, et al. (2005) LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro-inflammatory cytokines and MMP-9 in macrophages. Immunology 114 272
189. RA Fava, E Notidis, J Hunt, et al. (2003) A role for the lymphotoxin/LIGHT axis in the pathogenesis of murine collagen-induced arthritis. J Immunol 171 115
190. KJ Warrington, S Takemura, JJ Goronzy and CM Wayland (2001) CD4+, CD28− T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems. Arthritis Rheum 44 13
191. K Hirota, H Yoshitomi, M Hashimoto, et al. (2007) Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med 204 2803
192. Y Yamanishi, K Hiyama, S Ishioka, et al. (1999) Telomerase activity in the synovial tissues of chronic inflammatory and non-inflammatory rheumatic diseases. Int J Mol Med 4 513
193. FM Brennan, AL Hayes, CJ Ciesielski, et al. (2002) Evidence that rheumatoid arthritis synovial T cells are similar to cytokine-activated T cells: involvement of phosphatidylinositol 3-kinase and nuclear factor kappaB pathways in tumor necrosis factor alpha production in rheumatoid arthritis. Arthritis Rheum 46 31
194. H Hata, N Sakaguchi, H Yoshitomi, et al. (2004) Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice. J Clin Invest 114 582
195. MA Quinn, PG Conaghan, PJ O’Connor, et al. (2005) Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomized, double-blind, placebo-controlled trial. Arthritis Rheum 52 27
196. H Wang, SA Marsters, T Baker, et al. (2001) TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice. Nat Immunol 2 632
197. TM Seyler, YW Park, S Takemura, et al. (2005) BLyS and APRIL in rheumatoid arthritis. J Clin Invest 115 3083
198. PP Tak, RM Thurlings, C Rossier, et al. (2008) Atacicept in patients with rheumatoid arthritis: results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating, single- and repeated-dose study. Arthritis Rheum 58 61
199. BE Clausen, SL Bridges Jr, JC Lavelle, et al. (1998) Clonally-related immunoglobulin VH domains and nonrandom use of DH gene segments in rheumatoid arthritis synovium. Mol Med 4 240
200. A Kavanaugh, S Rosengren, SJ Lee, et al. (2008) Assessment of rituximab's immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results. Ann Rheum Dis 67 402
201. S Takemura, PA Klimiuk, A Braun, et al. (2001) T cell activation in rheumatoid synovium is B cell dependent. J Immunol 167 4710
202. F Humby, M Bombardieri, A Manzo, et al. (2009) Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium. PLoS Med 6 e1
203. KP MacDonald, AR Pettit, C Quinn, et al. (1999) Resistance of rheumatoid synovial dendritic cells to the immunosuppressive effects of IL-10. J Immunol 163 5599
204. DG Malone, RL Wilder, AM Saavedra-Delgado and DD Metcalfe (1987) Mast cell numbers in rheumatoid synovial tissues. Arthritis Rheum 30 130
205. DM Lee, DS Friend, MF Gurish, et al. (2002) Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 297 1689
206. A Juurikivi, C Sandler, KA Lindstedt, et al. (2005) Inhibition of c-kit tyrosine kinase by imatinib mesylate induces apoptosis in mast cells in rheumatoid synovia: a potential approach to the treatment of arthritis. Ann Rheum Dis 64 1126
207. AJ Hueber, DL Asquith, AM Miller, et al. (2010) Mast cells express IL-17A in rheumatoid arthritis synovium. J Immunol 184 3336
208. PP Tak, JA Kummer, CE Hack, et al. (1994) Granzyme-positive cytotoxic cells are specifically increased in early rheumatoid synovial tissue. Arthritis Rheum 37 1735
209. N Dalbeth, R Gundle, RJ Davies, et al. (2004) CD56bright NK cells are enriched at inflammatory sites and can engage with monocytes in a reciprocal program of activation. J Immunol 173 6418
210. L Marinova-Mutafchieva, RO Williams, K Funa, et al. (2002) Inflammation is preceded by tumor necrosis factor-dependent infiltration of mesenchymal cells in experimental arthritis. Arthritis Rheum 46 507
211. G Schett and GS Firestein (2010) Mr Outside and Mr Inside: classic and alternative views on the pathogenesis of rheumatoid arthritis. Ann Rheum Dis 69 787
212. S Bugatti, R Caporali, A Manzo, et al. (2005) Involvement of subchondral bone marrow in rheumatoid arthritis: lymphoid neogenesis and in situ relationship to subchondral bone marrow osteoclast recruitment. Arthritis Rheum 52 3448
213. J-M Waldurger and GS Firestein (2010) Neural regulation of synovial inflammation. Curr Rheumatol Rep 12 370-378
214. DL Boyle, TL Jones, D Hammaker, et al. (2006) Regulation of peripheral inflammation by spinal p38 MAP kinase in rats. PLoS Med 3(9), e338
215. Z Han, DL Boyle, AM Manning and GS Firestein (1998) AP-1 and NF-κB regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimmunity 28 197
216. GS Firestein (2004) The T cell cometh: interplay between adaptive immunity and cytokine networks in rheumatoid arthritis. J Clin Invest 114 471
217. A Fukushima, DL Boyle, M Corr and GS Firestein (2010) Kinetic analysis of synovial signalling and gene expression in animal models of arthritis. Ann Rheum Dis 69 918
218. H Liao, J Wu, E Kuhn, et al. (2004) Use of mass spectrometry to identify protein biomarkers of disease severity in the synovial fluid and serum of patients with rheumatoid arthritis. Arthritis Rheum 50 3792
219. H Jonsson, P Allen and SL Peng (2005) Inflammatory arthritis requires Foxo3a to prevent Fas ligand-induced neutrophil apoptosis. Nat Med 11 666
220. GS Firestein, AE Berger, DE Tracey, et al. (1992) IL-1 receptor antagonist protein production and gene expression in rheumatoid arthritis and osteoarthritis synovium. J Immunol 149 1054
221. MM Maurice, H Nakamura, EA van der Voort, et al. (1997) Evidence for the role of an altered redox state in hyporesponsiveness of synovial T cells in rheumatoid arthritis. Immunology 158 1458
222. CE Vergunst, DM Gerlag, H Dinant, et al. (2007) Blocking the receptor for C5a in patients with rheumatoid arthritis does not reduce synovial inflammation. Rheumatology (Oxford) 46 1773
223. I Siegle, T Klein, JT Backman, et al. (1998) Expression of cyclooxygenase 1 and cyclooxygenase 2 in human synovial tissue: differential elevation of cyclooxygenase 2 in inflammatory joint diseases. Arthritis Rheum 41 122
224. C Yao, D Sakata, Y Esaki, et al. (2009) Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nat Med 15 633
225. J Elmgreen, N Haagen and I Ahnfelt-Ronne (1987) Enhanced capacity for release of leukotriene B4 by neutrophils in rheumatoid arthritis. Ann Rheum Dis 46 501
226. JSH Gaston, AB Rickinson, QY Yao and MA Epstein (1986) The abnormal cytotoxic T cell response to Epstein-Barr virus in rheumatoid arthritis is correlated with disease activity and occurs in other arthropathies. Ann Rheum Dis 45 932
227. JJ Goronzy and CM Weyand (2001) Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. Trends Immunol 22 251
228. EN Unemori, MJ Bair, EA Bauer and EP Amento (1991) Stromelysin expression regulates collagenase activation in human fibroblasts. Dissociable control of two metalloproteinases by interferon-gamma. J Biol Chem 266 23477
229. GS Firestein, WD Xu, K Townsend, et al. (1988) Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. J Exp Med 168 1573
230. K Raza, F Falciani, SJ Curnow, et al. (2005) Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther 7 R784
231. M Chabaud, JM Durand, N Buchs, et al. (1999) Human interleukin-17: a T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 43 963
232. MI Koenders, E Lubberts, FA van de Loo, et al. (2006) Interleukin-17 acts independently of TNF-alpha under arthritic conditions. J Immunol 176 6262
233. MC Genovese, F Van den Bosch, SA Roberson, et al. (2010) LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum 62 929
234. MR Ehrenstein, JG Evans, A Singh, S Moore, et al. (2004) Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Med 200 277
235. CR Ruprecht, M Gattorno, F Ferlito, et al. (2005) Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia. J Exp Med 201 1793
236. S Xinqiang, L Fei, L Nan, et al. (2010) Therapeutic efficacy of experimental rheumatoid arthritis with low-dose methotrexate by increasing partially CD4(+)CD25(+)Treg cells and inducing Th1 to Th2 shift in both cells and cytokines. Biomed Pharmacother 64 463-471
237. ME Morgan, R Flierman, LM van Duivenvoorde, et al. (2005) Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells. Arthritis Rheum 52 2212
238. P Chomarat, J Banchereau and P Miossec (1995) Differential effects of interleukins 10 and 4 on the production of interleukin-6 by blood and synovium monocytes in rheumatoid arthritis. Arthritis Rheum 38 1046
239. KD Katsikis, CQ Chu, FM Brennan, et al. (1994) Immunoregulatory role of interleukin 10 in rheumatoid arthritis. J Exp Med 179 1517
240. LA Joosten, E Lubberts, P Durez, et al. (1997) Role of interleukin-4 and interleukin-10 in murine collagen-induced arthritis: protective effect of interleukin-4 and interleukin-10 treatment on cartilage destruction. Arthritis Rheum 40 249
241. LAB Joosten, E Lubberts, MMA Helsen and WB van den Berg (1997) Dual role of IL-12 in early and late stages of murine collagen type II arthritis. J Immunol 159 4094
242. W Hueber, DD Patel, T Dryja, et al. (2010) Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2 52ra72
243. TJ Smeets, MC Kraan, J Versendaal, et al. (1999) Analysis of serial synovial biopsies in patients with rheumatoid arthritis: description of a control group without clinical improvement after treatment with interleukin 10 or placebo. J Rheumatol 26 2089
244. D Burger, R Rezzonico, JM Li, et al. (1998) Imbalance between interstitial collagenase and tissue inhibitor of metalloproteinases 1 in synoviocytes and fibroblasts upon direct contact with stimulated T lymphocytes: involvement of membrane-associated cytokines. Arthritis Rheum 41 1748
245. IB McInnes, BP Leung, RD Sturrock, et al. (1997) Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis. Nat Med 3 189-195
246. GS Firestein, JM Alvaro-Gracia and R Maki (1990) Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol 144 3347
247. MC Genovese, S Cohen, L Moreland, et al. (2004) Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum 50 1412
248. LA Joosten, FA van De Loo, E Lubberts, et al. (2000) An IFN-gamma-independent proinflammatory role of IL-18 in murine streptococcal cell wall arthritis. J Immunol 165 6553
249. D Xu, HR Jiang, P Kewin, et al. (2008) IL-33 exacerbates antigen-induced arthritis by activating mast cells. Proc Natl Acad Sci U S A 105 10913
250. S Georgopoulos, D Plows and G Kollias (1996) Transmembrane TNF is sufficient to induce localized tissue toxicity and chronic inflammatory arthritis in transgenic mice. J Inflamm 46 86
251. RO Williams, LJ Mason, M Feldmann and RN Maini (1994) Synergy between anti-CD4 and anti-tumor necrosis factor in the amelioration of established collagen-induced arthritis. Proc Natl Acad Sci U S A 91 2762
252. PE Lipsky, DM van der Heijde, EW St Clair, et al. (2000) Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. N Engl J Med 343 1594
253. N Nishimoto, K Yoshizaki, N Miyasaka, et al. (2004) Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 50 1761
254. B Baslund, N Tvede, B Danneskiold-Samsoe, et al. (2005) Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study. Arthritis Rheum 52 2686
255. LA Joosten, MG Netea, SH Kim, et al. (2006) IL-32, a proinflammatory cytokine in rheumatoid arthritis. Proc Natl Acad Sci U S A 103 3298
256. WD Xu, GS Firestein, R Taetle, et al. (1989) Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions. J Clin Invest 83 876
257. AE Koch, SL Kunkel, JC Burrows, et al. (1991) Synovial tissue macrophage as a source of the chemotactic cytokine IL-8. J Immunol 147 2187
258. AE Koch, SL Kunkel, LA Harlow, et al. (1994) Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis. J Clin Invest 94 1012
259. C Schmutz, A Hulme, A Burman, et al. (2005) Chemokine receptors in the rheumatoid synovium: upregulation of CXCR5. Arthritis Res Ther 7 R217
260. T Nanki, Y Urasaki, T Imai, et al. (2004) Inhibition of fractalkine ameliorates murine collagen-induced arthritis. J Immunol 173 7010
261. JJ Haringman, TJ Smeets, P Reinders-Blankert and PP Tak (2006) Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis. Ann Rheum Dis 65 294
262. M Camps, T Ruckle, H Ji, et al. (2005) Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med 11 936
263. M Malyak, RE Swaney and WP Arend (1993) Levels of synovial fluid interleukin-1 receptor antagonist in rheumatoid arthritis and other arthropathies: potential contribution from synovial fluid neutrophils. Arthritis Rheum 36 781
264. RA Fava, NJ Olsen, G Spencer-Green, et al. (1994) Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue. J Exp Med 180 34
265. M Sioud, O Mellbye and O Forre (1998) Analysis of the NF-kappa B p65 subunit, Fas antigen, Fas ligand and Bcl-2–related proteins in the synovium of RA and polyarticular JRA. Clin Exp Rheumatol 16 125
266. PP Tak, DM Gerlag, KB Aupperle, et al. (2001) Inhibitor of nuclear factor kappaB kinase beta is a key regulator of synovial inflammation. Arthritis Rheum 44 1897
267. Z Han, DL Boyle, AM Manning and GS Firestein (1998) AP-1 and NF-κB regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimmunity 28 197
268. S Wakisaka, N Suzuki, N Saito, et al. (1998) Possible correction of abnormal rheumatoid arthritis synovial cell function by jun D transfection in vitro. Arthritis Rheum 41 470
269. D Hammaker and GS Firestein (2010) “Go upstream, young man”: lessons learned from the p38 saga. Ann Rheum Dis 69(Suppl 1), i77
270. Z Han, DL Boyle, L Chang, et al. (2001) c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 108 73
271. T Inoue, DL Boyle, M Corr, et al. (2006) Mitogen-activated protein kinase kinase 3 is a pivotal pathway regulating p38 activation in inflammatory arthritis. Proc Natl Acad Sci U S A 103 5484
272. T Inoue, D Hammaker, DL Boyle and GS Firestein (2006) Regulation of JNK by MKK-7 in fibroblast-like synoviocytes. Arthritis Rheum 54 2127
273. JG Walker, MJ Ahern, M Coleman, et al. (2007) Characterisation of a dendritic cell subset in synovial tissue which strongly expresses Jak/STAT transcription factors from patients with rheumatoid arthritis. Ann Rheum Dis 66 992
274. R Stillie, SM Farooq, JR Gordon and AW Stadnyk (2009) The functional significance behind expressing two IL-8 receptor types on PMN. J Leukoc Biol 86 529
275. M Huckel, U Schurigt, AH Wagner, et al. (2005) Attenuation of murine antigen-induced arthritis by treatment with a decoy oligodeoxynucleotide inhibiting signal transducer and activator of transcription-1 (STAT-1). Arthritis Res Ther 8 R17
276. TC van der Pouw Kraan, FA van Gaalen, PV Kasperkovitz, et al. (2003) Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues. Arthritis Rheum 48 2132
277. SE Sweeney, D Hammaker, DL Boyle and GS Firestein (2005) Regulation of c-Jun phosphorylation by the I kappa B kinase-epsilon complex in fibroblast-like synoviocytes. J Immunol 174 6424
278. SE Sweeney, TB Kimbler and GS Firestein (2010) Synoviocyte innate immune responses: II. Pivotal role of IFN regulatory factor 3. J Immunol 184 7162-7168
279. M Corr, DL Boyle, L Ronacher, et al. (2009) Synergistic benefit in inflammatory arthritis by targeting I kappaB kinase epsilon and interferon beta. Ann Rheum Dis 68 257
280. ME Weinblatt, A Kavanaugh, R Burgos-Vargas, et al. (2008) Treatment of rheumatoid arthritis with a Syk kinase inhibitor: a twelve-week, randomized, placebo-controlled trial. Arthritis Rheum 58 3309
281. CT Chou, JS Yang and MR Lee (2001) Apoptosis in rheumatoid arthritis: expression of Fas, Fas-L, p53, and Bcl-2 in rheumatoid synovial tissues. J Pathol 193 110
282. J Morel, R Audo, M Hahne and B Combe (2005) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rheumatoid arthritis synovial fibroblast proliferation through mitogen-activated protein kinases and phosphatidylinositol 3-kinase/Akt. J Biol Chem 280 15709
283. AI Catrina, AK Ulfgren, S Lindblad, et al. (2002) Low levels of apoptosis and high FLIP expression in early rheumatoid arthritis synovium. Ann Rheum Dis 61 934
284. HS Cha, S Rosengren, DL Boyle and GS Firestein (2006) PUMA regulation and proapoptotic effects in fibroblast-like synoviocytes. Arthritis Rheum 254 587
285. T Pap, JK Franz, KM Hummel, et al. (2000) Activation of synovial fibroblasts in rheumatoid arthritis: lack of expression of the tumour suppressor PTEN at sites of invasive growth and destruction. Arthritis Res 2 59
286. Q Yao, DW Seol, Z Mi and PD Robbins (2005) Intra-articular injection of recombinant TRAIL induces synovial apoptosis and reduces inflammation in a rabbit knee model of arthritis. Arthritis Res Ther 8 R16
287. JC Scatizzi, J Hutcheson, RM Pope, et al. (2010) Bim-Bcl-2 homology 3 mimetic therapy is effective at suppressing inflammatory arthritis through the activation of myeloid cell apoptosis. Arthritis Rheum 62 441
288. Q Yao, S Wang, JC Glorioso, et al. (2001) Gene transfer of p53 to arthritic joints stimulates synovial apoptosis and inhibits inflammation. Mol Ther 3 901
289. Y Yamanishi, DL Boyle, MJ Pinkoski, et al. (2002) Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis. Am J Pathol 160 123
290. E Simelyte, S Rosengren, DL Boyle, et al. (2005) Regulation of arthritis by p53: critical role of adaptive immunity. Arthritis Rheum 52(6), 1876-1884
291. GS Firestein, K Nguyen, K Aupperle, et al. (1996) Apoptosis in rheumatoid arthritis: p53 overexpression in rheumatoid arthritis synovium. Am J Pathol 149 2143
292. GS Firestein, F Echeverri, M Yeo, et al. (1997) Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. Proc Natl Acad Sci U S A 94 10895
293. SH Lee, DK Chang, A Goel, et al. (2003) Microsatellite instability and suppressed DNA repair enzyme expression in rheumatoid arthritis. J Immunol 170 2214
294. E Izquierdo, JD Cañete, R Celis, et al. (2009) Immature blood vessels in rheumatoid synovium are selectively depleted in response to anti-TNF therapy. PLoS One 4 e8131
295. CR Stevens, DR Blake, P Merry, et al. (1991) A comparative study by morphometry of the microvasculature in normal and rheumatoid synovium. Arthritis Rheum 34 1508
296. T Cramer, Y Yamanishi, BE Clausen, et al. (2003) HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell 112 645
297. AE Koch, MM Halloran, CJ Haskell, et al. (1995) Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature 376 517
298. DJ Peacock, ML Banquerigo and E Brahn (1992) Angiogenesis inhibition suppresses collagen arthritis. J Exp Med 175 1135
299. J Shankar, PB Thippegowda and SA Kanum (2009) Inhibition of HIF-1alpha activity by BP-1 ameliorates adjuvant induced arthritis in rats. Biochem Biophys Res Commun 387 223
300. CM Storgard, DG Stupack, A Jonczyk, et al. (1998) Decreased angiogenesis and arthritis in rabbits treated with an αvβ3 antagonist. J Clin Invest 103 47
301. DM Gerlag, E Borges, PP Tak, et al. (2001) Suppression of murine collagen-induced arthritis by targeted apoptosis of synovial neovasculature. Arthritis Res 3 357
302. LP Hale, ME Martin, DE McCollum, et al. (1989) Immunohistologic analysis of the distribution of cell adhesion molecules within the inflammatory synovial microenvironment. Arthritis Rheum 32 22
303. TB Issekutz and AC Issekutz (1991) T lymphocyte migration to arthritic joints and dermal inflammation in the rat: differing migration patterns and the involvement of VLA-4. Clin Immunol Immunopathol 61 436
304. MJ Elices, V Tsai and D Strahl (1994) et al: Expression and functional significance of alternatively spliced CS1 fibronectin in rheumatoid arthritis microvasculature. J Clin Invest 93 405-416
305. C Jorgensen, A Travaglio-Encinoza and C Bologna (1994) Human mucosal lymphocyte marker expression in synovial fluid lymphocytes of patients with rheumatoid arthritis. J Rheumatol 21 1602
306. C Jorgensen, I Couret, F Canovas, et al. (1996) Mononuclear cell retention in rheumatoid synovial tissue engrafted in severe combined immunodeficient (SCID) mice is up-regulated by tumour necrosis factor-alpha (TNF-alpha) and mediated through intercellular adhesion molecule-1 (ICAM-1). Clin Exp Immunol 106 20
307. JH Ruth, MA Amin, JM Woods, et al. (2005) Accelerated development of arthritis in mice lacking endothelial selectins. Arthritis Res Ther 7 R959
308. DM Lee, HP Kiener, SK Agarwal, et al. (2007) Cadherin-11 in synovial lining formation and pathology in arthritis. Science 315 1006
309. GC Wolfe, KL MacNaul, FF Buechel, et al. (1993) Differential in vivo expression of collagenase messenger RNA in synovium and cartilage: quantitative comparison with stromelysin messenger RNA levels in human rheumatoid arthritis and osteoarthritis patients and in two animal models of acute inflammatory arthritis. Arthritis Rheum 36 1540
310. GS Firestein, MM Paine and BH Littman (1991) Gene expression (collagenase, tissue inhibitor of metalloproteinases, complement, and HLA-DR) in rheumatoid arthritis and osteoarthritis synovium: quantitative analysis and effect of intraarticular corticosteroids. Arthritis Rheum 34 1094
311. JS Mudgett, NI Hutchinson, NA Chartrain, et al. (1998) Susceptibility of stromelysin 1–deficient mice to collagen-induced arthritis and cartilage destruction. Arthritis Rheum 41 110
312. R Lemaire, G Huet, F Zerimech, et al. (1997) Selective induction of the secretion of cathepsins B and L by cytokines in synovial fibroblast-like cells. Br J Rheumatol 36 735
313. WS Hou, W Li, G Keyszer, et al. (2002) Comparison of cathepsins K and S expression within the rheumatoid and osteoarthritic synovium. Arthritis Rheum 46 663
314. L Svelander, H Erlandsson-Harris, L Astner, et al. (2009) Inhibition of cathepsin K reduces bone erosion, cartilage degradation and inflammation evoked by collagen-induced arthritis in mice. Eur J Pharmacol 613 155
315. MW Lark, EK Bayne, J Flanagan, et al. (1997) Aggrecan degradation in human cartilage: evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints. J Clin Invest 100 93
316. Y Yamanishi, DL Boyle, M Clark, et al. (2002) Expression and regulation of aggrecanase in arthritis: the role of TGF-beta. J Immunol 168 1405
317. H Stanton, FM Rogerson, CJ East, et al. (2005) ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature 434 648
318. GS Firestein, MM Paine and DL Boyle (1994) Mechanisms of methotrexate action in rheumatoid arthritis: selective decrease in synovial collagenase gene expression. Arthritis Rheum 37 193
319. YY Kong, U Feige, I Sarosi, et al. (1999) Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402 304-309
320. S Kotake, N Udagawa, M Hakoda, et al. (2001) Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients. Arthritis Rheum 44 1003
321. A Deodhar, RK Dore, D Mandel, et al. (2010) Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients. Arthritis Care Res 62 569
322. D Diarra, M Stolina, K Polzer, et al. (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13 156
323. M Sen, M Chamorro, J Reifert, et al. (2001) Blockade of Wnt-5A/frizzled 5 signaling inhibits rheumatoid synoviocyte activation. Arthritis Rheum 44 772
324. RJ Lories and FP Luyten (2005) Bone morphogenetic protein signaling in joint homeostasis and disease. Cytokine Growth Factor Rev 16 287