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Synovial cellular and molecular markers in rheumatoid arthritis

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Abstract

The profound alterations in the structure, cellular composition, and function of synovial tissue in rheumatoid arthritis (RA) are the basis for the persistent inflammation and cumulative joint destruction that are hallmarks of this disease. In RA, the synovium develops characteristics of a tertiary lymphoid organ, with extensive infiltration of lymphocytes and myeloid cells. Concurrently, the fibroblast-like synoviocytes undergo massive hyperplasia and acquire a tissue-invasive phenotype. In this review, we summarize key components of these processes, focusing on recently-described roles of selected molecular markers of these cellular components of RA synovitis.

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References

  1. Pap T et al (2000) Fibroblast biology. Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis. Arthritis Res 2:361–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Put S et al (2014) Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques. Arthritis Res Ther 16:208

    Article  PubMed  PubMed Central  Google Scholar 

  3. Valencia X et al (2004) Cadherin-11 provides specific cellular adhesion between fibroblast-like synoviocytes. J Exp Med 200:1673–1679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Noss EH et al (2015) Evidence for cadherin-11 cleavage in the synovium and partial characterization of its mechanism. Arthritis Res Ther 17:126

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Pap T et al (2001) Invasiveness of synovial fibroblasts is regulated by p53 in the SCID mouse in vivo model of cartilage invasion. Arthritis Rheum 44:676–681

    Article  CAS  PubMed  Google Scholar 

  6. Lefevre S et al (2009) Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med 15:1414–1420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mor A et al (2005) The fibroblast-like synovial cell in rheumatoid arthritis: a key player in inflammation and joint destruction. Clin Immunol 115:118–128

    Article  CAS  PubMed  Google Scholar 

  8. Crofford LJ et al (1994) Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues. Effects of interleukin-1 beta, phorbol ester, and corticosteroids. J Clin Invest 93:1095–1101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yamada R et al (2000) Selective inhibition of cyclooxygenase-2 with antisense oligodeoxynucleotide restricts induction of rat adjuvant-induced arthritis. Biochem Biophys Res Commun 269:415–421

    Article  CAS  PubMed  Google Scholar 

  10. Pap T, et al. 2000. Fibroblast biology. Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis. In: Arthritis Res, p 361–367

  11. Yamanishi Y, Firestein GS (2001) Pathogenesis of rheumatoid arthritis: the role of synoviocytes. [review] [119 refs]. Rheum Dis Clin N Am 27:355–371

    Article  CAS  Google Scholar 

  12. Tolboom TC et al (2002) Invasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10. Ann Rheum Dis 61:975–980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sabeh F et al (2010) Membrane-type I matrix metalloproteinase-dependent regulation of rheumatoid arthritis synoviocyte function. J Immunol 184:6396–6406

    Article  CAS  PubMed  Google Scholar 

  14. Qin S et al (2015) Immunolocalization of membrane-type 1 MMP in human rheumatoid synovium tissues. Int J Clin Exp Pathol 8:9286–9292

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Koch AE et al (1991) Synovial tissue macrophage as a source of the chemotactic cytokine Il-8. J Immunol 147:2187–2195

    CAS  PubMed  Google Scholar 

  16. Koch AE et al (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258:1798–1801

    Article  CAS  PubMed  Google Scholar 

  17. Koch AE et al (1994) Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis. J Clin Invest 94:1012–1018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Koch AE et al (1992) Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis. J Clin Invest 90:772–779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Koch AE et al (1994) Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for macrophages in rheumatoid arthritis J Clin Invest 93:921–928

    CAS  PubMed  Google Scholar 

  20. Ruth JH et al (2001) Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis. Arthritis Rheum 44:1568–1581

    Article  CAS  PubMed  Google Scholar 

  21. Ruth JH et al (2003) Role of macrophage inflammatory protein-3alpha and its ligand CCR6 in rheumatoid arthritis. Lab Investig 83:579–588

    Article  CAS  PubMed  Google Scholar 

  22. Ruth JH et al (2006) CXCL16-mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway. Arthritis Rheum 54:765–778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Shahrara S et al (2005) Amelioration of rat adjuvant-induced arthritis by Met-RANTES. Arthritis Rheum 52:1907–1919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Shahrara S et al (2006) RANTES modulates TLR4-induced cytokine secretion in human peripheral blood monocytes. J Immunol 177:5077–5087

    Article  CAS  PubMed  Google Scholar 

  25. Kokkonen H et al (2010) Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum 62:383–391

    CAS  PubMed  Google Scholar 

  26. Ogura N et al (2005) Tumor necrosis factor-alpha increases chemokine gene expression and production in synovial fibroblasts from human temporomandibular joint. J Oral Pathol Med 34:357–363

    Article  CAS  PubMed  Google Scholar 

  27. Morgan R et al (2015) Expression and function of aminopeptidase N/CD13 produced by fibroblast-like synoviocytes in rheumatoid arthritis: role of CD13 in chemotaxis of cytokine-activated T cells independent of enzymatic activity. Arthritis Rheumatol 67:74–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Morgan RL et al (2016) Localization, shedding, regulation and function of aminopeptidase N/CD13 on fibroblast like Synoviocytes. PLoS One 11:e0162008

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Strieter RM et al (1995) The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem 270:27348–27357

    Article  CAS  PubMed  Google Scholar 

  30. Girbal-Neuhauser E et al (1999) The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro) filaggrin by deimination of arginine residues. J Immunol 162:585–594

    CAS  PubMed  Google Scholar 

  31. Schellekens GA et al (1998) Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 101:273–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mastronardi FG et al (2006) Increased citrullination of histone H3 in multiple sclerosis brain and animal models of demyelination: a role for tumor necrosis factor-induced peptidylarginine deiminase 4 translocation. J Neurosci 26:11387–11396

    Article  CAS  PubMed  Google Scholar 

  33. Yoshida K et al (2014) Citrullination of epithelial neutrophil-activating peptide 78/CXCL5 results in conversion from a non-monocyte-recruiting chemokine to a monocyte-recruiting chemokine. Arthritis Rheumatol 66:2716–2727

    Article  CAS  PubMed  Google Scholar 

  34. Ling S et al (2013) Citrullinated calreticulin potentiates rheumatoid arthritis shared epitope signaling. Arthritis Rheum 65:618–626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Isozaki T et al (2014) Inhibitor of DNA binding 1 as a secreted angiogenic transcription factor in rheumatoid arthritis. Arthritis Res Ther 16:R68

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Edhayan G et al (2016) Inflammatory properties of inhibitor of DNA binding 1 secreted by synovial fibroblasts in rheumatoid arthritis. Arthritis Res Ther 18:87

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Bourdonnay E et al (2015) Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial cells blunts inflammatory signaling. J Exp Med 212:729–742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lefevre S et al (2015) Role of synovial fibroblasts in rheumatoid arthritis. Curr Pharm Des 21:130–141

    Article  CAS  PubMed  Google Scholar 

  39. Muller-Ladner U et al (2007) Cells of the synovium in rheumatoid arthritis. Synovial fibroblasts Arthritis Res Ther 9:223

    Article  PubMed  CAS  Google Scholar 

  40. Bartok B, Firestein GS (2010) Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev 233:233–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mulherin D et al (1996) Synovial tissue macrophage populations and articular damage in rheumatoid arthritis. Arthritis Rheum 39:115–124

    Article  CAS  PubMed  Google Scholar 

  42. Davignon JL et al (2013) Targeting monocytes/macrophages in the treatment of rheumatoid arthritis. Rheumatology (Oxford) 52:590–598

    Article  CAS  Google Scholar 

  43. McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429–442

    Article  CAS  PubMed  Google Scholar 

  44. Athanasou NA (1995) Synovial macrophages. Ann Rheum Dis 54:392–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Epelman S et al (2014) Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40:91–104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Merad M et al (2002) Langerhans cells renew in the skin throughout life under steady-state conditions. Nat Immunol 3:1135–1141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bain CC et al (2014) Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat Immunol 15:929–937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tamoutounour S et al (2013) Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39:925–938

    Article  CAS  PubMed  Google Scholar 

  49. Ingersoll MA et al (2011) Monocyte trafficking in acute and chronic inflammation. Trends Immunol 32:470–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Geissmann F et al (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82

    Article  CAS  PubMed  Google Scholar 

  51. Si Y et al (2010) CCR2 mediates hematopoietic stem and progenitor cell trafficking to sites of inflammation in mice. J Clin Invest 120:1192–1203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Boring L et al (1997) Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. J Clin Invest 100:2552–2561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Serbina NV, Pamer EG (2006) Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7:311–317

    Article  CAS  PubMed  Google Scholar 

  54. Hamilton JA (2008) Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 8:533–544

    Article  CAS  PubMed  Google Scholar 

  55. Croxford AL et al (2015) The cytokine GM-CSF drives the inflammatory signature of CCR2+ monocytes and licenses autoimmunity. Immunity 43:502–514

    Article  CAS  PubMed  Google Scholar 

  56. Serbina NV et al (2008) Monocyte-mediated defense against microbial pathogens. Annu Rev Immunol 26:421–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Barbalat R et al (2009) Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands. Nat Immunol 10:1200–1207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Audoy-Remus J et al (2008) Rod-shaped monocytes patrol the brain vasculature and give rise to perivascular macrophages under the influence of proinflammatory cytokines and angiopoietin-2. J Neurosci 28:10187–10199

    Article  CAS  PubMed  Google Scholar 

  59. Ziegler-Heitbrock L et al (2010) Nomenclature of monocytes and dendritic cells in blood. Blood 116:e74–e80

    Article  CAS  PubMed  Google Scholar 

  60. Cros J et al (2010) Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 33:375–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wong KL et al (2011) Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood 118:e16–e31

    Article  CAS  PubMed  Google Scholar 

  62. Rossol M et al (2012) The CD14(bright) CD16+ monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population. Arthritis Rheum 64:671–677

    Article  CAS  PubMed  Google Scholar 

  63. Yoon BR et al (2014) Functional phenotype of synovial monocytes modulating inflammatory T-cell responses in rheumatoid arthritis (RA). PLoS One 9:e109775

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Coulthard LR et al (2012) Differential effects of infliximab on absolute circulating blood leucocyte counts of innate immune cells in early and late rheumatoid arthritis patients. Clin Exp Immunol 170:36–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Cauli A et al (1997) Interleukin-1, interleukin-1 receptor antagonist and macrophage populations in rheumatoid arthritis synovial membrane. Br J Rheumatol 36:935–940

    Article  CAS  PubMed  Google Scholar 

  66. Koller M et al (1999) Expression of adhesion molecules on synovial fluid and peripheral blood monocytes in patients with inflammatory joint disease and osteoarthritis. Ann Rheum Dis 58:709–712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kinne RW et al (2000) Macrophages in rheumatoid arthritis. Arthritis Res 2:189–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. van Amelsfort JM et al (2007) Proinflammatory mediator-induced reversal of CD4+,CD25+ regulatory T cell-mediated suppression in rheumatoid arthritis. Arthritis Rheum 56:732–742

    Article  PubMed  CAS  Google Scholar 

  69. Evans HG et al (2009) In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses. Proc Natl Acad Sci U S A 106:6232–6237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Yeadon C, Karsh J (1983) Lymphapheresis in rheumatoid arthritis. The clinical and laboratory effects of a limited course of cell depletion. Clin Exp Rheumatol 1:119–124

    CAS  PubMed  Google Scholar 

  71. Hahn G et al (1993) Modulation of monocyte activation in patients with rheumatoid arthritis by leukapheresis therapy. J Clin Invest 91:862–870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ramprasad MP et al (1996) Cell surface expression of mouse macrosialin and human CD68 and their role as macrophage receptors for oxidized low density lipoprotein. Proc Natl Acad Sci U S A 93:14833–14838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Tak PP et al (1997) Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity. Arthritis Rheum 40:217–225

    Article  CAS  PubMed  Google Scholar 

  74. Bresnihan B et al (2007) Synovial macrophages as a biomarker of response to therapeutic intervention in rheumatoid arthritis: standardization and consistency across centers. J Rheumatol 34:620–622

    PubMed  Google Scholar 

  75. Strobl H et al (1995) Flow cytometric analysis of intracellular CD68 molecule expression in normal and malignant haemopoiesis. Br J Haematol 90:774–782

    Article  CAS  PubMed  Google Scholar 

  76. Haringman JJ et al (2005) Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis 64:834–838

    Article  CAS  PubMed  Google Scholar 

  77. Van Gorp H et al (2010) Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell-directed therapy. Mol Immunol 47:1650–1660

    Article  CAS  PubMed  Google Scholar 

  78. Fonseca JE et al (2002) Macrophage subpopulations in rheumatoid synovium: reduced CD163 expression in CD4+ T lymphocyte-rich microenvironments. Arthritis Rheum 46:1210–1216

    Article  CAS  PubMed  Google Scholar 

  79. Bleesing J et al (2007) The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis. Arthritis Rheum 56:965–971

    Article  CAS  PubMed  Google Scholar 

  80. Mantovani A et al (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25:677–686

    Article  CAS  PubMed  Google Scholar 

  81. Lawrence T, Natoli G (2011) Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol 11:750–761

    Article  CAS  PubMed  Google Scholar 

  82. Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Gordon S, Martinez FO (2010) Alternative activation of macrophages: mechanism and functions. Immunity 32:593–604

    Article  CAS  PubMed  Google Scholar 

  84. Mantovani A et al (2005) Macrophage polarization comes of age. Immunity 23:344–346

    Article  CAS  PubMed  Google Scholar 

  85. Murray PJ et al (2014) Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41:14–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Xue J et al (2014) Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 40:274–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Campbell IK et al (2000) The colony-stimulating factors and collagen-induced arthritis: exacerbation of disease by M-CSF and G-CSF and requirement for endogenous M-CSF. J Leukoc Biol 68:144–150

    CAS  PubMed  Google Scholar 

  88. Cook AD et al (2001) Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease. Arthritis Res 3:293–298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Cornish AL et al (2009) G-CSF and GM-CSF as therapeutic targets in rheumatoid arthritis. Nat Rev Rheumatol 5:554–559

    Article  CAS  PubMed  Google Scholar 

  90. Duby AD et al (1989) Clonal heterogeneity of synovial fluid T lymphocytes from patients with rheumatoid arthritis. Proc Natl Acad Sci U S A 86:6206–6210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Brennan FM et al (2008) Resting CD4+ effector memory T cells are precursors of bystander-activated effectors: a surrogate model of rheumatoid arthritis synovial T-cell function. Arthritis Res Ther 10:R36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Brennan FM 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 46:31–41

    Article  CAS  PubMed  Google Scholar 

  93. Tran CN et al (2007) Molecular interactions between T cells and fibroblast-like synoviocytes: role of membrane tumor necrosis factor-alpha on cytokine-activated T cells. Am J Pathol 171:1588–1598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Tran CN et al (2008) Interactions of T cells with fibroblast-like synoviocytes: role of the B7 family costimulatory ligand B7-H3. J Immunol 180:2989–2998

    Article  CAS  PubMed  Google Scholar 

  95. Tsai C et al (1996) Responsiveness of human T lymphocytes to bacterial superantigens presented by cultured rheumatoid arthritis synoviocytes. Arthritis Rheum 39:125–136

    Article  CAS  PubMed  Google Scholar 

  96. Tran CN et al (2007) Presentation of arthritogenic peptide to antigen-specific T cells by fibroblast-like synoviocytes. Arthritis Rheum 56:1497–1506

    Article  CAS  PubMed  Google Scholar 

  97. Roberts CA et al (2015) The interplay between monocytes/macrophages and CD4(+) T cell subsets in rheumatoid arthritis. Front Immunol 6:571

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Rao DA et al (2017) Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature 542:110–114

    Article  CAS  PubMed  Google Scholar 

  99. Lebre MC, et al. 2016. Synovial IL-21/TNF-producing CD4+ T cells induce joint destruction in rheumatoid arthritis by inducing matrix metalloproteinase production by fibroblast-like synoviocytes. J Leukoc Biol

  100. Xing R et al (2016) Interleukin-21 induces migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis. Clin Exp Immunol 184:147–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Cooles FA et al (2013) Treg cells in rheumatoid arthritis: an update. Curr Rheumatol Rep 15:352

    Article  PubMed  CAS  Google Scholar 

  102. Weyand CM, Goronzy JJ (2003) Ectopic germinal center formation in rheumatoid synovitis. Ann N Y Acad Sci 987:140–149

    Article  CAS  PubMed  Google Scholar 

  103. Dennis G Jr et al (2014) Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics. Arthritis Res Ther 16:R90

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Hu F et al (2016) Hypoxia-inducible factor-1alpha perpetuates synovial fibroblast interactions with T cells and B cells in rheumatoid arthritis. Eur J Immunol 46:742–751

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Rheumatology and the Clinical Autoimmunity Center of Excellence, University of Michigan, Ann Arbor, MI, USA

    M. Asif Amin, David A. Fox & Jeffrey H. Ruth

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  1. M. Asif Amin
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  2. David A. Fox
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  3. Jeffrey H. Ruth
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Correspondence to David A. Fox.

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This article is a contribution to the special issue on Immunopathology of Rheumatoid Arthritis - Guest Editors: Cem Gabay and Paul Hasler

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Asif Amin, M., Fox, D.A. & Ruth, J.H. Synovial cellular and molecular markers in rheumatoid arthritis. Semin Immunopathol 39, 385–393 (2017). https://doi.org/10.1007/s00281-017-0631-3

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