Emerging aspects of molecular biomarkers for diagnosis, prognosis and treatment response in rheumatoid arthritis

References

• McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365:2205–2219.
   PubMed Web of Science ®Google Scholar
• Bosello S, Fedele AL, Peluso G, et al. Very early rheumatoid arthritis is the major predictor of major outcomes: clinical ACR remission and radiographic non-progression. Ann Rheum Dis. 2011;70:1292–1295.
   PubMed Web of Science ®Google Scholar
• Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569–2581.
   PubMed Web of Science ®Google Scholar
• Ungethuem U, Haeupl T, Witt H, et al. Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis. Physiol Genomics. 2010;42A:267–282.
   PubMed Web of Science ®Google Scholar
• Yoshida S, Arakawa F, Higuchi F, et al. Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarray combined with laser microdissection: up-regulation of inflammation-associated STAT1, IRF1, CXCL9, CXCL10, and CCL5. Scand J Rheumatol. 2012;41:170–179.
   PubMed Web of Science ®Google Scholar
• Lubbers J, Brink M, van de Stadt LA, et al. The type I IFN signature as a biomarker of preclinical rheumatoid arthritis. Ann Rheum Dis. 2013;72:776–780.
   PubMed Web of Science ®Google Scholar
• Lubbers J, Vosslamber S, van de Stadt LA, et al. B cell signature contributes to the prediction of RA development in patients with arthralgia. Ann Rheum Dis. 2015;74:1786–1788.
   PubMed Web of Science ®Google Scholar
• van Baarsen LG, Bos WH, Rustenburg F, et al. Gene expression profiling in autoantibody-positive patients with arthralgia predicts development of arthritis. Arthritis Rheum. 2010;62:694–704.
   PubMed Web of Science ®Google Scholar
• Pratt AG, Swan DC, Richardson S, et al. A CD4 T cell gene signature for early rheumatoid arthritis implicates interleukin 6-mediated STAT3 signalling, particularly in anti-citrullinated peptide antibody-negative disease. Ann Rheum Dis. 2012;71:1374–1381.
   PubMed Web of Science ®Google Scholar
• Anderson AE, Pratt AG, Sedhom MA, et al. IL-6-driven STAT signalling in circulating CD4+ lymphocytes is a marker for early anticitrullinated peptide antibody-negative rheumatoid arthritis. Ann Rheum Dis. 2016;75:466–473.
   PubMed Web of Science ®Google Scholar
• Long L, Li R, Li Y, et al. Pattern-based diagnosis and screening of differentially expressed serum proteins for rheumatoid arthritis by proteomic fingerprinting. Rheumatol Int. 2011;31:1069–1074.
   PubMed Web of Science ®Google Scholar
• Li XJ, Xu M, Zhao XQ, et al. Proteomic analysis of synovial fibroblast-like synoviocytes from rheumatoid arthritis. Clin Exp Rheumatol. 2013;31:552–558.
   PubMed Web of Science ®Google Scholar
• Zhang H, Fan LY, Zong M, et al. Proteins related to the functions of fibroblast-like synoviocytes identified by proteomic analysis. Clin Exp Rheumatol. 2012;30:213–221.
   PubMed Web of Science ®Google Scholar
• Baillet A, Trocme C, Berthier S, et al. Synovial fluid proteomic fingerprint: S100A8, S100A9 and S100A12 proteins discriminate rheumatoid arthritis from other inflammatory joint diseases. Rheumatology (Oxford). 2010;49:671–682.
   PubMed Web of Science ®Google Scholar
• Grazio S, Razdorov G, Erjavec I, et al. Differential expression of proteins with heparin affinity in patients with rheumatoid and psoriatic arthritis: a preliminary study. Clin Exp Rheumatol. 2013;31:665–671.
   PubMed Web of Science ®Google Scholar
• McArdle A, Butt AQ, Szentpetery A, et al. Developing clinically relevant biomarkers in inflammatory arthritis: a multi-platform approach for serum candidate protein discovery. Proteomics Clin Appl. Forthcoming 2016. in press.
   Google Scholar
• Kang MJ, Park YJ, You S, et al. Urinary proteome profile predictive of disease activity in rheumatoid arthritis. J Proteome Res. 2014;13:5206–5217.
   PubMed Web of Science ®Google Scholar
• Young SP, Kapoor SR, Viant MR, et al. The impact of inflammation on metabolomic profiles in patients with arthritis. Arthritis Rheum. 2013;65:2015–2023.
   PubMed Web of Science ®Google Scholar
• Madsen RK, Lundstedt T, Gabrielsson J, et al. Diagnostic properties of metabolic perturbations in rheumatoid arthritis. Arthritis Res Ther. 2011;13:R19.
   PubMed Web of Science ®Google Scholar
• Zabek A, Swierkot J, Malak A, et al. Application of (1)H NMR-based serum metabolomic studies for monitoring female patients with rheumatoid arthritis. J Pharm Biomed Anal. 2016;117:544–550.
   PubMed Web of Science ®Google Scholar
• Yang XY, Zheng KD, Lin K, et al. Energy metabolism disorder as a contributing factor of rheumatoid arthritis: a comparative proteomic and metabolomic study. Plos One. 2015;10:e0132695.
   PubMed Web of Science ®Google Scholar
• Kang KY, Lee SH, Jung SM, et al. Downregulation of tryptophan-related metabolomic profile in rheumatoid arthritis synovial fluid. J Rheumatol. 2015;42:2003–2011.
   PubMed Web of Science ®Google Scholar
• Karlson EW, Chibnik LB, Kraft P, et al. Cumulative association of 22 genetic variants with seropositive rheumatoid arthritis risk. Ann Rheum Dis. 2010;69:1077–1085.
   PubMed Web of Science ®Google Scholar
• Kurreeman F, Liao K, Chibnik L, et al. Genetic basis of autoantibody positive and negative rheumatoid arthritis risk in a multi-ethnic cohort derived from electronic health records. Am J Hum Genet. 2011;88:57–69.
   PubMed Web of Science ®Google Scholar
• Maehlen MT, Olsen IC, Andreassen BK, et al. Genetic risk scores and number of autoantibodies in patients with rheumatoid arthritis. Ann Rheum Dis. 2015;74:762–768.
   PubMed Web of Science ®Google Scholar
• Prahalad S, Conneely KN, Jiang Y, et al. Susceptibility to childhood-onset rheumatoid arthritis: investigation of a weighted genetic risk score that integrates cumulative effects of variants at five genetic loci. Arthritis Rheum. 2013;65:1663–1667.
   PubMed Web of Science ®Google Scholar
• Yarwood A, Han B, Raychaudhuri S, et al. A weighted genetic risk score using all known susceptibility variants to estimate rheumatoid arthritis risk. Ann Rheum Dis. 2015;74:170–176.
   PubMed Web of Science ®Google Scholar
• Nakano K, Whitaker JW, Boyle DL, et al. DNA methylome signature in rheumatoid arthritis. Ann Rheum Dis. 2013;72:110–117.
   PubMed Web of Science ®Google Scholar
• Liu Y, Aryee MJ, Padyukov L, et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat Biotechnol. 2013;31:142–147.
   PubMed Web of Science ®Google Scholar
• Huber R, Hummert C, Gausmann U, et al. Identification of intra-group, inter-individual, and gene-specific variances in mRNA expression profiles in the rheumatoid arthritis synovial membrane. Arthritis Res Ther. 2008;10:R98.
   PubMed Web of Science ®Google Scholar
• Lorenz P, Ruschpler P, Koczan D, et al. From transcriptome to proteome: differentially expressed proteins identified in synovial tissue of patients suffering from rheumatoid arthritis and osteoarthritis by an initial screen with a panel of 791 antibodies. Proteomics. 2003;3:991–1002.
   PubMed Web of Science ®Google Scholar
• Sha N, Vannucci M, Brown PJ, et al. Gene selection in arthritis classification with large-scale microarray expression profiles. Comp Funct Genomics. 2003;4:171–181.
   PubMedGoogle Scholar
• van der Pouw Kraan TC, van Gaalen FA, Kasperkovitz PV, et al. Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues. Arthritis Rheum. 2003;48:2132–2145.
   PubMed Web of Science ®Google Scholar
• Nzeusseu Toukap A, Galant C, Theate I, et al. Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus. Arthritis Rheum. 2007;56:1579–1588.
   PubMed Web of Science ®Google Scholar
• Batliwalla FM, Li W, Ritchlin CT, et al. Microarray analyses of peripheral blood cells identifies unique gene expression signature in psoriatic arthritis. Mol Med. 2005;11:21–29.
   PubMed Web of Science ®Google Scholar
• Batliwalla FM, Baechler EC, Xiao X, et al. Peripheral blood gene expression profiling in rheumatoid arthritis. Genes Immun. 2005;6:388–397.
   PubMed Web of Science ®Google Scholar
• van der Pouw Kraan TC, Wijbrandts CA, van Baarsen LG, et al. Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients. Ann Rheum Dis. 2007;66:1008–1014.
   PubMed Web of Science ®Google Scholar
• Liu Z, Sokka T, Maas K, et al. Prediction of disease severity in patients with early rheumatoid arthritis by gene expression profiling. Hum Genomics Proteomics. 2009;2009:484351.
   PubMedGoogle Scholar
• Reynolds RJ, Cui X, Vaughan LK, et al. Gene expression patterns in peripheral blood cells associated with radiographic severity in African Americans with early rheumatoid arthritis. Rheumatol Int. 2013;33:129–137.
   PubMed Web of Science ®Google Scholar
• Lauridsen MB, Bliddal H, Christensen R, et al. 1H NMR spectroscopy-based interventional metabolic phenotyping: a cohort study of rheumatoid arthritis patients. J Proteome Res. 2010;9:4545–4553.
   PubMed Web of Science ®Google Scholar
• Knevel R, Klein K, Somers K, et al. Identification of a genetic variant for joint damage progression in autoantibody-positive rheumatoid arthritis. Ann Rheum Dis. 2014;73:2038–2046.
   PubMed Web of Science ®Google Scholar
• de Rooy DP, Tsonaka R, Andersson ML, et al. Genetic factors for the severity of ACPA-negative rheumatoid arthritis in 2 cohorts of early disease: a genome-wide study. J Rheumatol. 2015;42:1383–1391.
   PubMed Web of Science ®Google Scholar
• Viatte S, Plant D, Han B, et al. Association of HLA-DRB1 haplotypes with rheumatoid arthritis severity, mortality, and treatment response. JAMA. 2015;313:1645–1656.
   PubMed Web of Science ®Google Scholar
• van Baarsen LG, Wijbrandts CA, Gerlag DM, et al. Pharmacogenomics of infliximab treatment using peripheral blood cells of patients with rheumatoid arthritis. Genes Immun. 2010;11:622–629.
   PubMed Web of Science ®Google Scholar
• van Baarsen LG, Wijbrandts CA, Rustenburg F, et al. Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment. Arthritis Res Ther. 2010;12:R11.
   PubMed Web of Science ®Google Scholar
• Wright HL, Thomas HB, Moots RJ, et al. Interferon gene expression signature in rheumatoid arthritis neutrophils correlates with a good response to TNFi therapy. Rheumatology (Oxford). 2015;54:188–193.
   PubMed Web of Science ®Google Scholar
• Toonen EJ, Gilissen C, Franke B, et al. Validation study of existing gene expression signatures for anti-TNF treatment in patients with rheumatoid arthritis. Plos One. 2012;7:e33199.
   PubMed Web of Science ®Google Scholar
• Thomson TM, Lescarbeau RM, Drubin DA, et al. Blood-based identification of non-responders to anti-TNF therapy in rheumatoid arthritis. BMC Med Genomics. 2015;8:26.
   PubMed Web of Science ®Google Scholar
• Raterman HG, Vosslamber S, de Ridder S, et al. The interferon type I signature towards prediction of non-response to rituximab in rheumatoid arthritis patients. Arthritis Res Ther. 2012;14:R95.
   PubMed Web of Science ®Google Scholar
• Sellam J, Marion-Thore S, Dumont F, et al. Use of whole-blood transcriptomic profiling to highlight several pathophysiologic pathways associated with response to rituximab in patients with rheumatoid arthritis: data from a randomized, controlled, open-label trial. Arthritis Rheumatol. 2014;66:2015–2025.
   PubMed Web of Science ®Google Scholar
• Thurlings RM, Boumans M, Tekstra J, et al. Relationship between the type I interferon signature and the response to rituximab in rheumatoid arthritis patients. Arthritis Rheum. 2010;62:3607–3614.
   PubMed Web of Science ®Google Scholar
• Vosslamber S, Raterman HG, van der Pouw Kraan TC, et al. Pharmacological induction of interferon type I activity following treatment with rituximab determines clinical response in rheumatoid arthritis. Ann Rheum Dis. 2011;70:1153–1159.
   PubMed Web of Science ®Google Scholar
• Gutierrez-Roelens I, Galant C, Theate I, et al. Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium. Arthritis Rheum. 2011;63:1246–1254.
   PubMed Web of Science ®Google Scholar
• Hogan VE, Holweg CT, Choy DF, et al. Pretreatment synovial transcriptional profile is associated with early and late clinical response in rheumatoid arthritis patients treated with rituximab. Ann Rheum Dis. 2012;71:1888–1894.
   PubMed Web of Science ®Google Scholar
• Mesko B, Poliska S, Szamosi S, et al. Peripheral blood gene expression and IgG glycosylation profiles as markers of tocilizumab treatment in rheumatoid arthritis. J Rheumatol. 2012;39:916–928.
   PubMed Web of Science ®Google Scholar
• Bansard C, Lequerre T, Derambure C, et al. Gene profiling predicts rheumatoid arthritis responsiveness to IL-1Ra (anakinra). Rheumatology (Oxford). 2011;50:283–292.
   PubMed Web of Science ®Google Scholar
• Ortea I, Roschitzki B, Ovalles JG, et al. Discovery of serum proteomic biomarkers for prediction of response to infliximab (a monoclonal anti-TNF antibody) treatment in rheumatoid arthritis: an exploratory analysis. J Proteomics. 2012;77:372–382.
   PubMed Web of Science ®Google Scholar
• Obry A, Hardouin J, Lequerre T, et al. Identification of 7 proteins in sera of RA patients with potential to predict ETA/MTX treatment response. Theranostics. 2015;5:1214–1224.
   PubMed Web of Science ®Google Scholar
• Kapoor SR, Filer A, Fitzpatrick MA, et al. Metabolic profiling predicts response to anti-tumor necrosis factor α therapy in patients with rheumatoid arthritis. Arthritis Rheum. 2013;65:1448–1456.
   PubMed Web of Science ®Google Scholar
• Priori R, Casadei L, Valerio M, et al. 1H-NMR-based metabolomic study for identifying serum profiles associated with the response to etanercept in patients with rheumatoid arthritis. Plos One. 2015;10:e0138537.
   Google Scholar
• Cui J, Stahl EA, Saevarsdottir S, et al. Genome-wide association study and gene expression analysis identifies CD84 as a predictor of response to etanercept therapy in rheumatoid arthritis. PLoS Genet. 2013;9:e1003394.
   PubMed Web of Science ®Google Scholar
• Julia A, Fernandez-Nebro A, Blanco F, et al. A genome-wide association study identifies a new locus associated with the response to anti-TNF therapy in rheumatoid arthritis. Pharmacogenomics J. 2016;16:147–150.
   PubMed Web of Science ®Google Scholar
• Cui J, Saevarsdottir S, Thomson B, et al. Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy. Arthritis Rheum. 2010;62:1849–1861.
   PubMed Web of Science ®Google Scholar
• Plant D, Prajapati R, Hyrich KL, et al. Replication of association of the PTPRC gene with response to anti-tumor necrosis factor therapy in a large UK cohort. Arthritis Rheum. 2012;64:665–670.
   PubMed Web of Science ®Google Scholar
• Liu C, Batliwalla F, Li W, et al. Genome-wide association scan identifies candidate polymorphisms associated with differential response to anti-TNF treatment in rheumatoid arthritis. Mol Med. 2008;14:575–581.
   PubMed Web of Science ®Google Scholar
• Krintel SB, Palermo G, Johansen JS, et al. Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNFα inhibitors in patients with rheumatoid arthritis. Pharmacogenet Genomics. 2012;22:577–589.
   PubMed Web of Science ®Google Scholar
• Acosta-Colman I, Palau N, Tornero J, et al. GWAS replication study confirms the association of PDE3A-SLCO1C1 with anti-TNF therapy response in rheumatoid arthritis. Pharmacogenomics. 2013;14:727–734.
   PubMed Web of Science ®Google Scholar
• Castro-Villegas C, Perez-Sanchez C, Escudero A, et al. Circulating miRNAs as potential biomarkers of therapy effectiveness in rheumatoid arthritis patients treated with anti-TNFalpha. Arthritis Res Ther. 2015;17:49.
   PubMed Web of Science ®Google Scholar
• Lequerre T, Gauthier-Jauneau AC, Bansard C, et al. Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis. Arthritis Res Ther. 2006;8:R105.
   PubMed Web of Science ®Google Scholar
• Drynda S, Ringel B, Kekow M, et al. Proteome analysis reveals disease-associated marker proteins to differentiate RA patients from other inflammatory joint diseases with the potential to monitor anti-TNFalpha therapy. Pathol Res Pract. 2004;200:165–171.
   PubMed Web of Science ®Google Scholar
• Sinz A, Bantscheff M, Mikkat S, et al. Mass spectrometric proteome analyses of synovial fluids and plasmas from patients suffering from rheumatoid arthritis and comparison to reactive arthritis or osteoarthritis. Electrophoresis. 2002;23:3445–3456.
   PubMed Web of Science ®Google Scholar
• Uchida T, Fukawa A, Uchida M, et al. Application of a novel protein biochip technology for detection and identification of rheumatoid arthritis biomarkers in synovial fluid. J Proteome Res. 2002;1:495–499.
   PubMed Web of Science ®Google Scholar
• Zheng X, Wu SL, Hincapie M, et al. Study of the human plasma proteome of rheumatoid arthritis. J Chromatogr A. 2009;1216:3538–3545.
   PubMed Web of Science ®Google Scholar
• de Seny D, Fillet M, Ribbens C, et al. Monomeric calgranulins measured by SELDI-TOF mass spectrometry and calprotectin measured by ELISA as biomarkers in arthritis. Clin Chem. 2008;54:1066–1075.
   PubMed Web of Science ®Google Scholar
• Liao H, Wu J, Kuhn E, et al. Use of mass spectrometry to identify protein biomarkers of disease severity in the synovial fluid and serum of patients with rheumatoid arthritis. Arthritis Rheum. 2004;50:3792–3803.
   PubMed Web of Science ®Google Scholar
• Obry A, Lequerre T, Hardouin J, et al. Identification of S100A9 as biomarker of responsiveness to the methotrexate/etanercept combination in rheumatoid arthritis using a proteomic approach. Plos One. 2014;9:e115800.
   PubMed Web of Science ®Google Scholar
• Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447:661–678.
   PubMed Web of Science ®Google Scholar
• Huizinga TW. Personalized medicine in rheumatoid arthritis: is the glass half full or half empty? J Intern Med. 2015;277:178–187.
   PubMed Web of Science ®Google Scholar
• Okada Y. From the era of genome analysis to the era of genomic drug discovery: a pioneering example of rheumatoid arthritis. Clin Genet. 2014;86:432–440.
   PubMed Web of Science ®Google Scholar
• Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987;30:1205–1213.
   PubMed Web of Science ®Google Scholar
• Holoshitz J. The rheumatoid arthritis HLA-DRB1 shared epitope. Curr Opin Rheumatol. 2010;22:293–298.
   PubMed Web of Science ®Google Scholar
• de Bakker PI, Raychaudhuri S. Interrogating the major histocompatibility complex with high-throughput genomics. Hum Mol Genet. 2012;21:R29–R36.
   PubMed Web of Science ®Google Scholar
• Jia X, Han B, Onengut-Gumuscu S, et al. Imputing amino acid polymorphisms in human leukocyte antigens. Plos One. 2013;8:e64683.
   PubMed Web of Science ®Google Scholar
• Raychaudhuri S, Sandor C, Stahl EA, et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet. 2012;44:291–296.
   PubMed Web of Science ®Google Scholar
• Okada Y, Wu D, Trynka G, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014;506:376–381.
   PubMed Web of Science ®Google Scholar
• Viatte S, Plant D, Raychaudhuri S. Genetics and epigenetics of rheumatoid arthritis. Nat Rev Rheumatol. 2013;9:141–153.
   PubMed Web of Science ®Google Scholar
• Carmona FD, Mackie SL, Martin JE, et al. A large-scale genetic analysis reveals a strong contribution of the HLA class II region to giant cell arteritis susceptibility. Am J Hum Genet. 2015;96:565–580.
   PubMed Web of Science ®Google Scholar
• van der Helm-van Mil AH, Toes RE, Huizinga TW. Genetic variants in the prediction of rheumatoid arthritis. Ann Rheum Dis. 2010;69:1694–1696.
   PubMed Web of Science ®Google Scholar
• Knevel R, Grondal G, Huizinga TW, et al. Genetic predisposition of the severity of joint destruction in rheumatoid arthritis: a population-based study. Ann Rheum Dis. 2012;71:707–709.
   PubMed Web of Science ®Google Scholar
• Wang J, Bansal AT, Martin M, et al. Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis. Pharmacogenomics J. 2013;13:235–241.
   PubMed Web of Science ®Google Scholar
• Plant D, Bowes J, Potter C, et al. 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. 2011;63:645–653.
   PubMed Web of Science ®Google Scholar
• Umicevic Mirkov M, Cui J, Vermeulen SH, et al. Genome-wide association analysis of anti-TNF drug response in patients with rheumatoid arthritis. Ann Rheum Dis. 2013;72:1375–1381.
   PubMed Web of Science ®Google Scholar
• Marquez A, Ferreiro-Iglesias A, Davila-Fajardo CL, et al. Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis. Arthritis Res Ther. 2014;16:R66.
   PubMed Web of Science ®Google Scholar
• Ferreiro-Iglesias A, Montes A, Perez-Pampin E, et al. Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis. Pharmacogenomics J. 2016;16:137–140.
   PubMed Web of Science ®Google Scholar
• Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010;376:1094–1108.
   PubMed Web of Science ®Google Scholar
• Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005;102:10604–10609.
   PubMed Web of Science ®Google Scholar
• Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28:1057–1068.
   PubMed Web of Science ®Google Scholar
• Klein K, Gay S. Epigenetics in rheumatoid arthritis. Curr Opin Rheumatol. 2015;27:76–82.
   PubMed Web of Science ®Google Scholar
• Karouzakis E, Gay RE, Michel BA, et al. DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum. 2009;60:3613–3622.
   PubMed Web of Science ®Google Scholar
• Karouzakis E, Gay RE, Gay S, et al. Increased recycling of polyamines is associated with global DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum. 2012;64:1809–1817.
   PubMed Web of Science ®Google Scholar
• Neidhart M, Karouzakis E, Jungel A, et al. Inhibition of spermidine/spermine N1-acetyltransferase activity: a new therapeutic concept in rheumatoid arthritis. Arthritis Rheumatol. 2014;66:1723–1733.
   PubMed Web of Science ®Google Scholar
• Whitaker JW, Shoemaker R, Boyle DL, et al. An imprinted rheumatoid arthritis methylome signature reflects pathogenic phenotype. Genome Med. 2013;5:40.
   PubMed Web of Science ®Google Scholar
• Ai R, Whitaker JW, Boyle DL, et al. DNA methylome signature in synoviocytes from patients with early rheumatoid arthritis compared to synoviocytes from patients with longstanding rheumatoid arthritis. Arthritis Rheumatol. 2015;67:1978–1980.
   PubMed Web of Science ®Google Scholar
• Cribbs AP, Kennedy A, Penn H, et al. Treg cell function in rheumatoid arthritis is compromised by ctla-4 promoter methylation resulting in a failure to activate the indoleamine 2,3-dioxygenase pathway. Arthritis Rheumatol. 2014;66:2344–2354.
   PubMed Web of Science ®Google Scholar
• Cribbs AP, Kennedy A, Penn H, et al. Methotrexate restores regulatory T cell function through demethylation of the FoxP3 upstream enhancer in patients with rheumatoid arthritis. Arthritis Rheumatol. 2015;67:1182–1192.
   PubMed Web of Science ®Google Scholar
• Trynka G, Sandor C, Han B, et al. Chromatin marks identify critical cell types for fine mapping complex trait variants. Nat Genet. 2013;45:124–130.
   PubMed Web of Science ®Google Scholar
• Engler A, Niederer F, Klein K, et al. SIRT6 regulates the cigarette smoke-induced signalling in rheumatoid arthritis synovial fibroblasts. J Mol Med (Berl). 2014;92:757–767.
   PubMed Web of Science ®Google Scholar
• Toussirot E, Wendling D, Herbein G. Biological treatments given in patients with rheumatoid arthritis or ankylosing spondylitis modify HAT/HDAC (histone acetyltransferase/histone deacetylase) balance. Joint Bone Spine. 2014;81:544–545.
   PubMed Web of Science ®Google Scholar
• Chen XM, Huang QC, Yang SL, et al. Role of micro RNAs in the pathogenesis of rheumatoid arthritis: novel perspectives based on review of the literature. Medicine. 2015;94:e1326.
   PubMed Web of Science ®Google Scholar
• Churov AV, Oleinik EK, Knip M. MicroRNAs in rheumatoid arthritis: altered expression and diagnostic potential. Autoimmun Rev. 2015;14:1029–1037.
   PubMed Web of Science ®Google Scholar
• Filkova M, Aradi B, Senolt L, et al. Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis. Ann Rheum Dis. 2014;73:1898–1904.
   PubMed Web of Science ®Google Scholar
• Lindstrom TM, Robinson WH. Biomarkers for rheumatoid arthritis: making it personal. Scand J Clin Lab Invest Suppl. 2010;242:79–84.
   PubMedGoogle Scholar