Chapter 96 : Future Perspectives for Rheumatoid Arthritis and Other Autoimmune Diseases

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Immunologic biomarkers are intrinsic to the field of rheumatology both for making a clinical diagnosis and in potentially detecting early signs of disease in at-risk individuals when symptoms are absent. In this brief chapter, we discuss developing and future directions in the use of biomarkers in rheumatology with an emphasis on rheumatoid arthritis. We discuss the role of the “mechanistic” biomarker, a subtype of the biomarker that measures a process directly linked to disease pathogenesis, thus increasing both diagnostic reliability and potentially identifying phenotype-targeted therapies. As such mechanistic biomarkers have begun a revolution in the approach to cancer, we attempt to provide parallels as to how such markers can be applied to diagnosis and targeted treatment in the rheumatic diseases.

Citation: Sokolove J. 2016. Future Perspectives for Rheumatoid Arthritis and Other Autoimmune Diseases, p 922-926. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch96
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1. Atkinson AJ Biomarkers Definitions Working Group . 2001. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69 : 89 95.[CrossRef]
2. Logothetis NK . 2008. What we can do and what we cannot do with fMRI. Nature 453 : 869 878.[CrossRef].[PubMed]
3. van Leeuwen MA, van Rijswijk MH, van der Heijde DM, Te Meerman GJ, van Riel PL, Houtman PM, van De Putte LB, Limburg PC . 1993. The acute-phase response in relation to radiographic progression in early rheumatoid arthritis: a prospective study during the first three years of the disease. Br J Rheumatol 32( Suppl 3) : 9 13.[PubMed]
4. Higgins MJ, Baselga J . 2011. Targeted therapies for breast cancer. J Clin Invest 121 : 3797 3803.[CrossRef].[PubMed]
5. Vossenaar ER, van Venrooij WJ . 2004. Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. Arthritis Res Ther 6 : 107 111.[CrossRef].[PubMed]
6. Ernst T, La Rosée P, Müller MC, Hochhaus A . 2011. BCR-ABL mutations in chronic myeloid leukemia. Hematol Oncol Clin North Am 25 : 997 1008, v vi.[CrossRef].[PubMed]
7. Sachdev JC, Jahanzeb M . 2012. Blockade of the HER family of receptors in the treatment of HER2-positive metastatic breast cancer. Clin Breast Cancer 12 : 19 29.[CrossRef].[PubMed]
8. Sequist LV, Martins RG, Spigel D, Grunberg SM, Spira A, Jänne PA, Joshi VA, McCollum D, Evans TL, Muzikansky A, Kuhlmann GL, Han M, Goldberg JS, Settleman J, Iafrate AJ, Engelman JA, Haber DA, Johnson BE, Lynch TJ . 2008. First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J Clin Oncol 26 : 2442 2449.[CrossRef].[PubMed]
9. Shaw AT, Engelman JA . 2014. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 370 : 2537 2539.[CrossRef].[PubMed]
10. Gainor JF, Shaw AT . 2013. Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist 18 : 865 875.[CrossRef].[PubMed]
11. Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis MC REFLEX Trial Group . 2006. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 54 : 2793 2806.[CrossRef].[PubMed]
12. Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh A, Racewicz AJ, van Vollenhoven RF, Li NF, Agarwal S, Hessey EW, Shaw TM DANCER Study Group . 2006. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 54 : 1390 1400.[CrossRef].[PubMed]
13. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J . 2004. NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20 : 319 325.[PubMed].[CrossRef]
14. Gattorno M, Piccini A, Lasigliè D, Tassi S, Brisca G, Carta S, Delfino L, Ferlito F, Pelagatti MA, Caroli F, Buoncompagni A, Viola S, Loy A, Sironi M, Vecchi A, Ravelli A, Martini A, Rubartelli A . 2008. The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 58 : 1505 1515.[CrossRef].[PubMed]
15. Allantaz F, Chaussabel D, Stichweh D, Bennett L, Allman W, Mejias A, Ardura M, Chung W, Smith E, Wise C, Palucka K, Ramilo O, Punaro M, Banchereau J, Pascual V . 2007. Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade. J Exp Med 204 : 2131 2144.[CrossRef].[PubMed]
16. Niewold TB, Hua J, Lehman TJ, Harley JB, Crow MK . 2007. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun 8 : 492 502.[CrossRef].[PubMed]
17. Boulé MW, Broughton C, Mackay F, Akira S, Marshak-Rothstein A, Rifkin IR . 2004. Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes. J Exp Med 199 : 1631 1640.[CrossRef].[PubMed]
18. Means TK, Latz E, Hayashi F, Murali MR, Golenbock DT, Luster AD . 2005. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest 115 : 407 417.[CrossRef].[PubMed]
19. Kelly KM, Zhuang H, Nacionales DC, Scumpia PO, Lyons R, Akaogi J, Lee P, Williams B, Yamamoto M, Akira S, Satoh M, Reeves WH . 2006. “Endogenous adjuvant” activity of the RNA components of lupus autoantigens Sm/RNP and Ro 60. Arthritis Rheum 54 : 1557 1567.[CrossRef].[PubMed]
20. Savarese E, Chae OW, Trowitzsch S, Weber G, Kastner B, Akira S, Wagner H, Schmid RM, Bauer S, Krug A . 2006. U1 small nuclear ribonucleoprotein immune complexes induce type I interferon in plasmacytoid dendritic cells through TLR7. Blood 107 : 3229 3234.[CrossRef].[PubMed]
21. Lövgren T, Eloranta ML, Kastner B, Wahren-Herlenius M, Alm GV, Rönnblom L . 2006. Induction of interferon-alpha by immune complexes or liposomes containing systemic lupus erythematosus autoantigen- and Sjögren's syndrome autoantigen-associated RNA. Arthritis Rheum 54 : 1917 1927.[CrossRef].[PubMed]
22. Niewold TB . 2011. Interferon alpha as a primary pathogenic factor in human lupus. J Interferon Cytokine Res 31 : 887 892.[CrossRef].[PubMed]
23. Hua J, Kirou K, Lee C, Crow MK . 2006. Functional assay of type I interferon in systemic lupus erythematosus plasma and association with anti-RNA binding protein autoantibodies. Arthritis Rheum 54 : 1906 1916.[CrossRef].[PubMed]
24. Yao Y, Richman L, Higgs BW, Morehouse CA, de los Reyes M, Brohawn P, Zhang J, White B, Coyle AJ, Kiener PA, Jallal B . 2009. Neutralization of interferon-alpha/beta-inducible genes and downstream effect in a phase I trial of an anti-interferon-alpha monoclonal antibody in systemic lupus erythematosus. Arthritis Rheum 60 : 1785 1796.[CrossRef].[PubMed]
25. Sokolove J, Zhao X, Chandra PE, Robinson WH . 2011. Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcγ receptor. Arthritis Rheum 63 : 53 62.[CrossRef].[PubMed]
26. Harre U, Georgess D, Bang H, Bozec A, Axmann R, Ossipova E, Jakobsson PJ, Baum W, Nimmerjahn F, Szarka E, Sarmay G, Krumbholz G, Neumann E, Toes R, Scherer HU, Catrina AI, Klareskog L, Jurdic P, Schett G . 2012. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 122 : 1791 1802.[CrossRef].[PubMed]
27. van Dongen H, van Aken J, Lard LR, Visser K, Ronday HK, Hulsmans HM, Speyer I, Westedt ML, Peeters AJ, Allaart CF, Toes RE, Breedveld FC, Huizinga TW . 2007. Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 56 : 1424 1432.[CrossRef].[PubMed]
28. Deane KD, O'Donnell CI, Hueber W, Majka DS, Lazar AA, Derber LA, Gilliland WR, Edison JD, Norris JM, Robinson WH, Holers VM . 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 3172.[CrossRef].[PubMed]
29. Kokkonen H, Söderström I, Rocklöv J, Hallmans G, Lejon K, Rantapää Dahlqvist S . 2010. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum 62 : 383 391.[CrossRef].[PubMed]
30. Sokolove J, Bromberg R, Deane KD, Lahey LJ, Derber LA, Chandra PE, Edison JD, Gilliland WR, Tibshirani RJ, Norris JM, Holers VM, Robinson WH . 2012. Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS One 7 : e35296.[CrossRef].[PubMed]
31. Stohl W, Hilbert DM . 2012. The discovery and development of belimumab: the anti-BLyS-lupus connection. Nat Biotechnol 30 : 69 77.[CrossRef].[PubMed]
32. Sokolove J, Johnson DS, Lahey LJ, Wagner CA, Cheng D, Thiele GM, Michaud K, Sayles H, Reimold AM, Caplan L, Cannon GW, Kerr G, Mikuls TR, Robinson WH . 2014. Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis. Arthritis Rheumatol 66 : 813 821.[CrossRef].[PubMed]
33. Kay J, Morgacheva O, Messing SP, Kremer JM, Greenberg JD, Reed GW, Gravallese EM, Furst DE . 2014. Clinical disease activity and acute phase reactant levels are discordant among patients with active rheumatoid arthritis: acute phase reactant levels contribute separately to predicting outcome at one year. Arthritis Res Ther 16 : R40.[CrossRef].[PubMed]
34. Sokolove J, Brennan MJ, Sharpe O, Lahey LJ, Kao AH, Krishnan E, Edmundowicz D, Lepus CM, Wasko MC, Robinson WH . 2013. Brief report: citrullination within the atherosclerotic plaque: a potential target for the anti-citrullinated protein antibody response in rheumatoid arthritis. Arthritis Rheum 65 : 1719 1724.[CrossRef].[PubMed]
35. El-Barbary AM, Kassem EM, El-Sergany MA, Essa SA, Eltomey MA . 2011. Association of anti-modified citrullinated vimentin with subclinical atherosclerosis in early rheumatoid arthritis compared with anti-cyclic citrullinated peptide. J Rheumatol 38 : 828 834.[CrossRef].[PubMed]
36. Syversen SW, Goll GL, van der Heijde D, Landewé R, Lie BA, Odegård S, Uhlig T, Gaarder PI, Kvien TK . 2010. Prediction of radiographic progression in rheumatoid arthritis and the role of antibodies against mutated citrullinated vimentin: results from a 10-year prospective study. Ann Rheum Dis 69 : 345 351.[CrossRef].[PubMed]
37. Thiele GM, Duryee MJ, Anderson DR, Klassen LW, Mohring SM, Young KA, Benissan-Messan D, Sayles H, Dusad A, Hunter CD, Sokolove J, Robinson WH, O'Dell JR, Nicholas AP, Tuma DJ, Mikuls TR . 2015. Malondialdehyde-acetaldehyde adducts and anti-malondialdehyde-acetaldehyde antibodies in rheumatoid arthritis. Arthritis Rheumatol 67 : 645 655.[CrossRef].[PubMed]
38. Charpin C, Martin M, Balandraud N, Roudier J, Auger I . 2010. Autoantibodies to BRAF, a new family of autoantibodies associated with rheumatoid arthritis. Arthritis Res Ther 12 : R194.[CrossRef].[PubMed]
39. Shi J, Knevel R, Suwannalai P, van der Linden MP, Janssen GM, van Veelen PA, Levarht NE, van der Helm-van Mil AH, Cerami A, Huizinga TW, Toes RE, Trouw LA . 2011. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc Natl Acad Sci USA 108 : 17372 17377.[CrossRef].[PubMed]
40. Curtis JR, van der Helm-van Mil AH, Knevel R, Huizinga TW, Haney DJ, Shen Y, Ramanujan S, Cavet G, Centola M, Hesterberg LK, Chernoff D, Ford K, Shadick NA, Hamburger M, Fleischmann R, Keystone E, Weinblatt ME . 2012. Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity. Arthritis Care Res (Hoboken) 64 : 1794 1803.[CrossRef]
41. Hughes-Austin JM, Deane KD, Derber LA, Kolfenbach JR, Zerbe GO, Sokolove J, Lahey LJ, Weisman MH, Buckner JH, Mikuls TR, O'Dell JR, Keating RM, Gregersen PK, Robinson WH, Holers VM, Norris JM . 2013. Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA). Ann Rheum Dis 72 : 901 907.[CrossRef].[PubMed]
42. Plant D, Bowes J, Potter C, Hyrich KL, Morgan AW, Wilson AG, Isaacs JD, Barton A Wellcome Trust Case Control Consortium, British Society for Rheumatology Biologics Register . 2011. Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci. Arthritis Rheum 63 : 645 653.[CrossRef].[PubMed]
43. Plant D, Thomson W, Lunt M, Flynn E, Martin P, Eyre S, Farragher T, Bunn D, Worthington J, Symmons D, Barton A . 2011. The role of rheumatoid arthritis genetic susceptibility markers in the prediction of erosive disease in patients with early inflammatory polyarthritis: results from the Norfolk Arthritis Register. Rheumatology (Oxford) 50 : 78 84.[CrossRef].[PubMed]
44. Oliver J, Plant D, Webster AP, Barton A . 2015. Genetic and genomic markers of anti-TNF treatment response in rheumatoid arthritis. Biomarkers Med 9 : 499 512.[CrossRef]
45. Plant D, Wilson AG, Barton A . 2014. Genetic and epigenetic predictors of responsiveness to treatment in RA. Nat Rev Rheumatol 10 : 329 337.[CrossRef].[PubMed]
46. Galligan CL, Siebert JC, Siminovitch KA, Keystone EC, Bykerk V, Perez OD, Fish EN . 2009. Multiparameter phospho-flow analysis of lymphocytes in early rheumatoid arthritis: implications for diagnosis and monitoring drug therapy. PLoS One 4 : e6703.[CrossRef].[PubMed]


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Current and future biomarkers for rheumatoid arthritis: diagnosis and prediction

Citation: Sokolove J. 2016. Future Perspectives for Rheumatoid Arthritis and Other Autoimmune Diseases, p 922-926. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch96

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