Objective and noninvasive biochemical markers in rheumatoid arthritis: where are we and where are we going?

References

• Pradeepkiran JA. Insights of rheumatoid arthritis risk factors and associations. J Transl Autoimmun. 2019;20:100012.
   Google Scholar
• Gavrilă BI, Ciofu C, Stoica V. Biomarkers in Rheumatoid Arthritis, what is new? J. Med Life. 2016;9:144–148.
   PubMedGoogle Scholar
• Sirotti S, Generali E, Ceribelli A, et al. Personalized medicine in rheumatology: the paradigm of serum autoantibodies. Autoimmun Highlights. 2017;8:1–13.
   PubMed Web of Science ®Google Scholar
• Mewar D, Wilson AG. Autoantibodies in rheumatoid arthritis: a review. Biomed Pharmacother. 2006;60(10):648–655.
   PubMed Web of Science ®Google Scholar
• Mam VD, Huizinga TWJ. An overview of autoantibodies in rheumatoid arthritis. J Autoimmun. 2020;110:102392.
   PubMed Web of Science ®Google Scholar
• Conigliaro P, Chimenti MS, Triggianese P, et al. Autoantibodies in inflammatory arthritis. Autoimmun Rev. 2016;15(7):673–683..
   Web of Science ®Google Scholar
• Rose HM, Ragan C, Pearce E, et al. No Title. Proc Soc Exp Biol Med [Internet]. 2020 Nov 9;68:1–6. cited];:. Available from…
   Google Scholar
• Waaler E. On the occurrence of afactor in human serum activating the specific agglutination of sheep blood corpuscles. Acta Pathol Microbiol Scand. 1940;17(2):172–188.
   Google Scholar
• Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Annals of Internal Medicine. 2007;146(11):797–808..
   PubMed Web of Science ®Google Scholar
• Nell VPK, Machold KP, Stamm TA, et al. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis. 2005;64(12):1731–1736..
   PubMed Web of Science ®Google Scholar
• Ingegnoli F, Castelli R, Gualtierotti R. Rheumatoid Factors: clinical Applications. Dis Markers [Internet]. 2021 Feb 19;35:727–734. cited] Available from. .
   Google Scholar
• Carubbi F, Alunno A, Gerli R, et al. Post-Translational Modifications of Proteins: novel Insights in the Autoimmune Response in Rheumatoid Arthritis. Cells. 2019;8(7):1–13..
   Web of Science ®Google Scholar
• Sun J, Zhang Y, Liu L, et al. Diagnostic accuracy of combined tests of anti cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis: a meta-analysis. Clin Exp Rheumatol. 2014;32(1):11–21.
   PubMed Web of Science ®Google Scholar
• Saeki Y, Kudo-Tanaka E, Ohshima S, et al. Baseline anti-citrullinated peptide antibody (ACPA) titers and serum interleukin-6 (IL-6) levels possibly predict progression of bone destruction in early stages of rheumatoid arthritis (ERA). Rheumatol Int. 2013;33(2):451–456..
   PubMed Web of Science ®Google Scholar
• Harrold LR, Litman HJ, Connolly SE, et al. Effect of anticitrullinated protein antibody status on response to abatacept or antitumor necrosis factor-α therapy in patients with rheumatoid arthritis: a us national observational study. J Rheumatol. 2018;45(1):32–39..
   PubMed Web of Science ®Google Scholar
• Reyes-Castillo Z, Palafox-Sánchez CA, Parra-Rojas I, et al. Comparative analysis of autoantibodies targeting peptidylarginine deiminase type 4, mutated citrullinated vimentin and cyclic citrullinated peptides in rheumatoid arthritis: associations with cytokine profiles, clinical and genetic features. Clin Exp Immunol. 2015;182(2):119–131..
   PubMed Web of Science ®Google Scholar
• Harre U, Georgess D, Bang H, et al. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest. 2012;122(5):1721–1802..
   Web of Science ®Google Scholar
• Aletaha D, Alasti F, Smolen JS. Rheumatoid factor determines structural progression of rheumatoid arthritis dependent and independent of disease activity. Ann Rheum Dis. 2013;72(6):875–880.
   PubMed Web of Science ®Google Scholar
• Aletaha D, Alasti F, Smolen JS. Rheumatoid factor, not antibodies against citrullinated proteins, is associated with baseline disease activity in rheumatoid arthritis clinical trials. Arthritis Res Ther. 2015;17(1):229.
   PubMedGoogle Scholar
• Tan YK, Li HH, Allen JC, et al. Anti-cyclic citrullinated peptide but not rheumatoid factor is associated with ultrasound-detected bone erosion among rheumatoid arthritis patients with at least moderate disease activity. Int J Rheum Dis. 2020;23(10):1337–1343..
   PubMed Web of Science ®Google Scholar
• Gudmann NS, Hansen NUB, Jensen ACB, et al. Biological relevance of citrullinations: diagnostic, prognostic and therapeutic options. Autoimmunity. 2015;48(2):73–79..
   PubMed Web of Science ®Google Scholar
• Spinelli FR, Pecani A, Conti F, et al. Post-translational modifications in rheumatoid arthritis and atherosclerosis: focus on citrullination and carbamylation. J Int Med Res. 2016;45(1_suppl):81–85..
   Google Scholar
• Trouw LA, Rispens T, Toes REM. Beyond citrullination: other post-translational protein modifications in rheumatoid arthritis. Nat Rev Rheumatol. 2017;13(6):331–339.
   PubMed Web of Science ®Google Scholar
• Ursum J, Bos WH, Van De Stadt RJ, et al. Different properties of ACPA and IgM-RF derived from a large dataset: further evidence of two distinct autoantibody systems. Arthritis Res Ther. 2009;11(3):R75..
   PubMed Web of Science ®Google Scholar
• Iwaszkiewicz C, Puszczewicz M, Bialkowska-Puszczewicz G. Diagnostic value of the anti-Sa antibody compared with the anti-cyclic citrullinated peptide antibody in rheumatoid arthritis. Int J Rheum Dis. 2015;18(1):46–51.
   PubMed Web of Science ®Google Scholar
• Wang X, Chen P, Cui J, et al. Keratin 8 is a novel autoantigen of rheumatoid arthritis. Biochem Biophys Res Commun. 2015;465(4):665–669..
   PubMed Web of Science ®Google Scholar
• Zhu T, Feng L. Comparison of anti-mutated citrullinated vimentin, anti-cyclic citrullinated peptides, anti-glucose-6-phosphate isomerase and anti-keratin antibodies and rheumatoid factor in the diagnosis of rheumatoid arthritis in Chinese patients. Int J Rheum Dis. 2013;16(2):157–161.
   PubMed Web of Science ®Google Scholar
• Snir O, Widhe M, Hermansson M, et al. Antibodies to several citrullinated antigens are enriched in the joints of rheumatoid arthritis patients. Arthritis Rheum. 2010;62(1):44–52..
   PubMedGoogle Scholar
• Dai ZW, Wang ZH, Dong YY, et al. Diagnostic value of anti-citrullinated fibrinogen antibody in rheumatoid arthritis: a meta-analysis. Int J Rheum Dis. 2019;22(4):599–607..
   PubMed Web of Science ®Google Scholar
• Koivula MK, Heliövaara M, Ramberg J, et al. Autoantibodies binding to citrullinated telopeptide of type II collagen and to cyclic citrullinated peptides predict synergistically the development of seropositive rheumatoid arthritis. Ann Rheum Dis. 2007;66(11):1450–1455..
   PubMed Web of Science ®Google Scholar
• Turunen S, Hannonen P, Koivula MK, et al. Separate and overlapping specificities in rheumatoid arthritis antibodies binding to citrulline- and homocitrulline-containing peptides related to type I and II collagen telopeptides. Arthritis Res Ther. 2015;17(1):2..
   PubMedGoogle Scholar
• Brink M, Verheul MK, Rönnelid J, et al. Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage. Arthritis Res Ther. 2015;17(1):25..
   PubMedGoogle Scholar
• Verheul MK, Böhringer S, Mam VD, et al. Triple Positivity for Anti–Citrullinated Protein Autoantibodies, Rheumatoid Factor, and Anti–Carbamylated Protein Antibodies Conferring High Specificity for Rheumatoid Arthritis: implications for Very Early Identification of At-Risk Individuals. Arthritis Rheumatol. 2018;70(11):1721–1731..
   PubMed Web of Science ®Google Scholar
• Challener GJ, Jones JD, Pelzek AJ, et al. Anti-carbamylated protein antibody levels correlate with anti-sa (citrullinated vimentin) antibody levels in rheumatoid arthritis. J Rheumatol. 2016;43(2):273–281..
   PubMed Web of Science ®Google Scholar
• Shi J, Knevel R, Suwannalai P, et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc Natl Acad Sci U S A. 2011;108(42):17372–17377..
   PubMed Web of Science ®Google Scholar
• Yee A, Webb T, Seaman A, et al. Anti-CarP antibodies as promising marker to measure joint damage and disease activity in patients with rheumatoid arthritis. Immunol Res. 2015;61(1–2):24–30..
   PubMed Web of Science ®Google Scholar
• Ajeganova S, Van Steenbergen HW, Verheul MK, et al. The association between anti-carbamylated protein (anti-CarP) antibodies and radiographic progression in early rheumatoid arthritis: a study exploring replication and the added value to ACPA and rheumatoid factor. Ann Rheum Dis. 2017;76(1).
   Web of Science ®Google Scholar
• Juarez M, Bang H, Hammar F, et al. Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis. Ann Rheum Dis. 2016;75(6):1099–1107..
   PubMed Web of Science ®Google Scholar
• Thurlings RM, Vos K, Wijbrandts CA, et al. Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response. Ann Rheum Dis. 2008;67(7):917–925..
   PubMed Web of Science ®Google Scholar
• Maneiro RJ, Salgado E, Carmona L, et al. Rheumatoid factor as predictor of response to abatacept, rituximab and tocilizumab in rheumatoid arthritis: systematic review and meta-analysis. Semin Arthritis Rheum. 2013;43(1):9–17..
   PubMed Web of Science ®Google Scholar
• El Fassi D, Banga JP, Gilbert JA, et al. Treatment of Graves’ disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies. Clin Immunol. 2009. DOI:10.1016/j.clim.2008.09.007.
   PubMed Web of Science ®Google Scholar
• Manz RA, Thiel A, Radbruch A. Lifetime of plasma cells in the bone marrow. Nature. 1997;388:133–134.
   PubMed Web of Science ®Google Scholar
• Mulhearn B, Barton A, Viatte S. Using the immunophenotype to predict response to biologic drugs in rheumatoid arthritis. J Pers Med. 2019;9:1–15.
   Web of Science ®Google Scholar
• Takeuchi T, Miyasaka N, Inui T, et al. High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: a post hoc analysis of the RISIN. Arthritis Res Ther. 2017;19:194.
   PubMed Web of Science ®Google Scholar
• Braun-Moscovici Y, Markovits D, Zinder O, et al. Anti-cyclic citrullinated protein antibodies as a predictor of response to anti-tumor necrosis factor-α therapy in patients with rheumatoid arthritis. J Rheumatol. 2006;33:497–500.
   PubMed Web of Science ®Google Scholar
• Klaasen R, Cantaert T, Wijbrandts CA, et al. The value of rheumatoid factor and anti-citrullinated protein antibodies as predictors of response to infliximab in rheumatoid arthritis: an exploratory study. Rheumatology (Oxford). 2011;50:1487–1493.
   PubMed Web of Science ®Google Scholar
• Lv Q, Yin Y, Li X, et al. The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNFα agent treatment in patients with rheumatoid arthritis: a meta-analysis. PLoS One. 2014;9:e89442.
   PubMed Web of Science ®Google Scholar
• Bos WH, Bartelds GM, Wolbink GJ, et al. Differential response of the rheumatoid factor and anticitrullinated protein antibodies during adalimumab treatment in patients with rheumatoid arthritis. J Rheumatol. 2008;35:1972–1977.
   PubMed Web of Science ®Google Scholar
• Takeuchi T, Matsubara T, Urata Y, et al. Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs. Mod Rheumatol. 2014;24:744–753.
   PubMed Web of Science ®Google Scholar
• Kawashiri SY, Kawakami A, Iwamoto N, et al. In rheumatoid arthritis patients treated with tocilizumab, the rate of clinical disease activity index (CDAI) remission at 24 weeks is superior in those with higher titers of IgM-rheumatoid factor at baseline. Mod Rheumatol. 2011;21:370–374.
   PubMed Web of Science ®Google Scholar
• Sokolove J, Pisetsky D. Bone loss, pain and inflammation: three faces of ACPA in RA pathogenesis. Ann Rheum Dis. 2016;75:637–639.
   PubMed Web of Science ®Google Scholar
• Leeming DJ, Bay-Jensen AC, Vassiliadis E, et al. Post-translational modifications of the extracellular matrix are key events in cancer progression: opportunities for biochemical marker development. Biomarkers. 2011;16:193–205.
   PubMed Web of Science ®Google Scholar
• Karsdal MAMA, Henriksen K, Leeming DJDJDJ, et al. Novel combinations of Post-Translational Modification (PTM) neo-epitopes provide tissue-specific biochemical markers-are they the cause or the consequence of the disease? Clin. Biochem. 2010;43:793–804.
   Web of Science ®Google Scholar
• Schellekens GA, Baw DJ, Fhj VDH, et al. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest. 1998;101:273–281.
   PubMed Web of Science ®Google Scholar
• Shi J, Van De Stadt LA, Levarht EWN, et al. Anti-carbamylated protein (anti-CarP) antibodies precede the onset of rheumatoid arthritis. Ann Rheum Dis. 2014;73:780–783.
   PubMed Web of Science ®Google Scholar
• Alavi A, Pool AJ, Axford JS. New insights into rheumatoid arthritis associated glycosylation changes. Adv Exp Med Biol. 2005;564:129–138.
   PubMed Web of Science ®Google Scholar
• Li Y, Zhou M, Lv X, et al. Reduced activity of HDAC3 and increased acetylation of histones H3 in peripheral blood mononuclear cells of patients with rheumatoid arthritis. J Immunol Res. 2018;2018:7313515.
   PubMed Web of Science ®Google Scholar
• Hitchon CA, El-Gabalawy HS. Oxidation in rheumatoid arthritis. Arthritis Res Ther. 2004;6:265–278.
   PubMed Web of Science ®Google Scholar
• Vossenaar ER, Radstake TRD, Van Der Heijden A, et al. Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Ann Rheum Dis. 2004;63:373–381.
   PubMed Web of Science ®Google Scholar
• Makrygiannakis D, Af Klint E, Lundberg IE, et al. Citrullination is an inflammation-dependent process. Ann Rheum Dis. 2006;65:1219–1222.
   PubMed Web of Science ®Google Scholar
• Spengler J, Lugonja B, Jimmy Ytterberg A, et al. Release of active peptidyl arginine deiminases by neutrophils can explain production of extracellular citrullinated autoantigens in rheumatoid arthritis synovial fluid. Arthritis Rheumatol. 2015;67:3135–3145.
   PubMed Web of Science ®Google Scholar
• Damgaard D, Bjørn ME, Steffensen MA, et al. Reduced glutathione as a physiological co-activator in the activation of peptidylarginine deiminase. Arthritis Res Ther. 2016;18:102.
   PubMed Web of Science ®Google Scholar
• Mortensen JH, Godskesen LE, Jensen MD, et al. Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn’s Disease from Ulcerative Colitis. J. Crohns. Colitis. 2015;9:863–872.
   Google Scholar
• Bay-Jensen AC, Wichuk S, Byrjalsen I, et al. Circulating Protein Fragments of Cartilage and Connective Tissue Degradation Are Diagnostic and Prognostic Markers of Rheumatoid Arthritis and Ankylosing Spondylitis. PLoS One. 2013;8:1–7.
   Web of Science ®Google Scholar
• Curran AM, Naik P, Giles JT, et al. PAD enzymes in rheumatoid effectors and autoimmune targets. Nat Rev Rheumatol. 2020;16:301-315.
   PubMed Web of Science ®Google Scholar
• Pruijn GJM. Citrullination and carbamylation in the pathophysiology of rheumatoid arthritis. Front Immunol. 2015;6:192.
   PubMed Web of Science ®Google Scholar
• Verheul MK, Van Veelen PA, Mam VD, et al. Pitfalls in the detection of citrullination and carbamylation. Autoimmun Rev. 2018;17:136–141.
   PubMed Web of Science ®Google Scholar
• Axford JS. Glycosylation and rheumatic disease. Biochim Biophys Acta - Mol Basis Dis. 1999;1455:219–229.
   PubMed Web of Science ®Google Scholar
• Scherer HU, Wang J, Toes REM, et al. Immunoglobulin 1 (IgG1) Fc-glycosylation profiling of anti-citrullinated peptide antibodies from human serum. Proteomics - Clin Appl. 2009;3:106–115.
   PubMed Web of Science ®Google Scholar
• Rombouts Y, Willemze A, Jjbc VB, et al. Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis. Ann Rheum Dis;75:578–585.https://ard.bmj.com/content/75/3/578
   PubMed Web of Science ®Google Scholar
• Phull AR, Nasir B. Haq I ul, et al. Oxidative Stress, Consequences and ROS Mediated Cellular Signaling in Rheumatoid Arthritis Chem Biol Interact. 2018;281:121–136.
   Google Scholar
• Foulquier C, Sebbag M, Clavel C, et al. Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis Rheum. 2007;56:3541–3553.
   PubMed Web of Science ®Google Scholar
• Damgaard D, Senolt L, Nielsen CH. Increased levels of peptidylarginine deiminase 2 in synovial fluid from anti-CCP-positive rheumatoid arthritis patients: association with disease activity and inflammatory markers. Rheumatol (United Kingdom). 2016;55:918–927.
   PubMed Web of Science ®Google Scholar
• Jjbc VB, Schwarte CM, Stammen-Vogelzangs J, et al. The rheumatoid arthritis synovial fluid citrullinome reveals novel citrullinated epitopes in apolipoprotein E, myeloid nuclear differentiation antigen, and β-actin. Arthritis Rheum. 2013;65:69–80.
   PubMedGoogle Scholar
• Kinloch A, Lundberg K, Wait R, et al. Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis. Arthritis Rheum. 2008;58:2287–2295.
   PubMed Web of Science ®Google Scholar
• Wang F, Chen FF, Gao WB, et al. Identification of citrullinated peptides in the synovial fluid of patients with rheumatoid arthritis using LC-MALDI-TOF/TOF. Clin Rheumatol. 2016;35:2185–2194.
   PubMed Web of Science ®Google Scholar
• Chapuy-Regaud S, Sebbag M, Baeten D, et al. Fibrin Deimination in Synovial Tissue Is Not Specific for Rheumatoid Arthritis but Commonly Occurs during Synovitides. J Immunol. 2005;174:5057–5064.
   PubMed Web of Science ®Google Scholar
• Tilvawala R, Nguyen SH, Maurais AJ, et al. The Rheumatoid Arthritis-Associated Citrullinome. Cell Chem Biol. 2018;25:691–704.
   PubMed Web of Science ®Google Scholar
• Bay-Jensen AC, Karsdal MA, Vassiliadis E, et al. Circulating citrullinated vimentin fragments reflect disease burden in ankylosing spondylitis and have prognostic capacity for radiographic progression. Arthritis Rheum. 2013;65:972–980.
   PubMed Web of Science ®Google Scholar
• Mortensen JH, Manon-Jensen T, Jensen MD, et al. Ulcerative colitis, Crohn’s disease, and irritable bowel syndrome have different profiles of extracellular matrix turnover, which also reflects disease activity in Crohn’s disease.PLoS One. 2017;12:e0185855.
   Google Scholar
• Acac B-J, Platt A, Byrjalsen I, et al. Effect of tocilizumab combined with methotrexate on circulating biomarkers of synovium, cartilage, and bone in the LITHE study. Semin Arthritis Rheum. 2014;43:470–478.
   PubMed Web of Science ®Google Scholar
• Blair JPMPM, Bager C, Platt A, et al. Identification of pathological RA endotypes using blood-based biomarkers reflecting tissue metabolism. A Retrospective and Explorative Analysis of Two Phase III RA Studies.PLoS One.2020;14:e0219980.
   Google Scholar
• Mortensen JHJH, Guo X, De Los Reyes M, et al. The VICM biomarker is released from activated macrophages and inhibited by anti-GM-CSFRα-mAb treatment in rheumatoid arthritis patients. Clin Exp Rheumatol. 2019;37:73–80.
   PubMed Web of Science ®Google Scholar
• Parekh RB, Isenberg DA, Ansell BM, et al. Galactosylation of IgG associated oligosaccharides: reduction in patients with adult and juvenile onset rheumatoid arthritis and relation to disease activity. Lancet. 1988;1:966–969.
   PubMed Web of Science ®Google Scholar
• Ercan A, Cui J, Chatterton DEW, et al. Aberrant IgG galactosylation precedes disease onset, correlates with disease activity, and is prevalent in autoantibodies in rheumatoid arthritis. Arthritis Rheum. 2010;62:2239–2248.
   PubMed Web of Science ®Google Scholar
• Takeshita M, Kuno A, Suzuki K, et al. Alteration of matrix metalloproteinase-3 O-glycan structure as a biomarker for disease activity of rheumatoid arthritis. Arthritis Res Ther. 2016;18:112.
   PubMed Web of Science ®Google Scholar
• Datta S, Kundu S, Ghosh P, et al. Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid arthritis. Clin Rheumatol. 2014;33:1557–1564.
   PubMed Web of Science ®Google Scholar
• Leeming DJ, Sand JM, Nnielsen MJ, et al. Serological investigation of the collagen degradation profile of patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis. Biomark Insights. 2012;7:119–126.
   PubMedGoogle Scholar
• Leeming DJ, Byrjalsen I, Jiménez W, et al. Protein fingerprinting of the extracellular matrix remodelling in a rat model of liver fibrosis-a serological evaluation. Liver Int. 2013;33:439–447.
   PubMed Web of Science ®Google Scholar
• Karsdal MA, Genovese F, Madsen EA, et al. Collagen and tissue turnover as a function of age: implications for fibrosis. J Hepatol. 2016;64:103–109.
   PubMed Web of Science ®Google Scholar
• Karsdal MAMA, Manon-Jensen T, Genovese F, et al. Novel insights into the function and dynamics of extracellular matrix in liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 2015;308:G807–G830.
   PubMed Web of Science ®Google Scholar
• Karsdal MA, Delvin E, Christiansen C. Protein fingerprints - relying on and understanding the information of serological protein measurements. Clin Biochem. 2011;44:1278–1279.
   PubMed Web of Science ®Google Scholar
• The Collagen R-BS. Family. Cold Spring Harb Perspect Biol. 2011;3:1–19.
   Web of Science ®Google Scholar
• Manon-Jensen T, Kjeld NG, Karsdal MA. Collagen-mediated hemostasis. J Thromb Haemost. 2016;14:438–448.
   PubMed Web of Science ®Google Scholar
• Heinegård D, Saxne T. The role of the cartilage matrix in osteoarthritis. Nat Rev Rheumatol. 2011;7:50–56.
   PubMed Web of Science ®Google Scholar
• Tseng S, Reddi AH, Di Cesare PE. Cartilage oligomeric matrix protein (COMP): a biomarker of arthritis. Biomark Insights. 2009;2009:33–44.
   Google Scholar
• Gudmann NSNS, Siebuhr ASAS, Christensen AFAF, et al. Type I and III collagen turnover is increased in axial spondyloarthritis and psoriatic arthritis. Associations with Disease Activity and Diagnostic Capacity Clin Exp Rheumatol. 2017;35:653–659.
   Google Scholar
• Gudmann NSNS, Munk HLHL, Christensen AFAF, et al. Chondrocyte activity is increased in psoriatic arthritis and axial spondyloarthritis. Arthritis Res Ther. 2016;18:141.
   PubMed Web of Science ®Google Scholar
• Maijer KIKI, Gudmann NSNS, Karsdal MAMA, et al. Neo-Epitopes–Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis. Pietropaolo M, Editor PLoS One. 2016;11:e0149329.
   PubMedGoogle Scholar
• Bay-Jensen AC, Platt A, Siebuhr AS, et al. Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study. Arthritis Res Ther. 2016;18:13.
   PubMed Web of Science ®Google Scholar
• Siebuhr AS, Petersen KK, Arendt-Nielsen L, et al. Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover. Osteoarthr Cartil. 2014;22:44–50.
   PubMed Web of Science ®Google Scholar
• Siebuhr AS, Bay-Jensen AC, Leeming DJ, et al. Serological identification of fast progressors of structural damage with rheumatoid arthritis. Arthritis Res Ther. 2013;15:R86.
   PubMed Web of Science ®Google Scholar
• Bay-Jensen AC, Leeming DJ, Kleyer A, et al. Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study. Rheumatol Int. 2012;32:3565–3572.
   PubMed Web of Science ®Google Scholar
• Østergaard M, Boesen M. Imaging in rheumatoid arthritis: the role of magnetic resonance imaging and computed tomography. Radiol Medica. 2019;124:1128–1141.
   PubMed Web of Science ®Google Scholar
• Van Der Kooij SM, Ypm G-R, De Vries-Bouwstra JK, et al. Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis. 2009;68:914–921.
   PubMed Web of Science ®Google Scholar
• Molenaar ETH, Voskuyl AE, Dinant HJ, et al. Progression of Radiologic Damage in Patients with Rheumatoid Arthritis in Clinical Remission. Arthritis Rheum. 2004;50:36–42.
   PubMed Web of Science ®Google Scholar
• Bruyn GAW, Pineda C, Hernandez-Diaz C, et al. Validity of ultrasonography and measures of adult shoulder function and reliability of ultrasonography in detecting shoulder synovitis in patients with rheumatoid arthritis using magnetic resonance imaging as a gold standard. Arthritis Care Res. 2010;62:1079–1086.
   PubMed Web of Science ®Google Scholar
• Saghafi M, Khodashahi M, Saadati N, et al. Relationship between cartilage oligomeric matrix protein (COMP) and rheumatoid arthritis severity. Electron Physician. 2017;9:5940–5947.
   PubMedGoogle Scholar
• Happonen KE, Saxne T, Aspberg A, et al. Regulation of complement by cartilage oligomeric matrix protein allows for a novel molecular diagnostic principle in rheumatoid arthritis. Arthritis Care Res. 2010;62:3574–3583.
   Google Scholar
• El Defrawy AO, Gheita TA, Raslan HM, et al. Oligomeres Knorpelmatrixprotein in Serum und Synovialflüssigkeit– konzentrationen bei früher und etablierter rheumatoider Arthritis. Z Rheumatol. 2016;75:917–923.
   PubMedGoogle Scholar
• Fujikawa K, Kawakami A, Tamai M, et al. High serum cartilage oligomeric matrix protein determines the subset of patients with early-stage rheumatoid arthritis with high serum C-reactive protein, matrix metalloproteinase-3, and MRI-proven bone erosion. J Rheumatol. 2009;36:1126–1129.
   PubMed Web of Science ®Google Scholar
• Andersson MLE, Svensson B, Petersson IF, et al. Early increase in serum-COMP is associated with joint damage progression over the first five years in patients with rheumatoid arthritis. BMC Musculoskelet Disord. 2013;14:229.
   PubMed Web of Science ®Google Scholar
• Young-Min S, Cawston T, Marshall N, et al. Biomarkers predict radiographic progression in early rheumatoid arthritis and perform well compared with traditional markers. Arthritis Rheum. 2007;56:3236–3247.
   PubMed Web of Science ®Google Scholar
• Charni N, Juillet F, Garnero P. Urinary type II collagen helical peptide (HELIX-II) as a new biochemical marker of cartilage degradation in patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum. 2005;52:1081–1090.
   PubMed Web of Science ®Google Scholar
• Rbm L, Geusens P, Dmfm VDH, et al. Arthritis instantaneously causes collagen type I and type II degradation in patients with early rheumatoid arthritis: a longitudinal analysis. Ann Rheum Dis. 2006;65:40–44.
   PubMed Web of Science ®Google Scholar
• Ben Achour W, Bouaziz M, Mechri M, et al. A cross sectional study of bone and cartilage biomarkers: correlation with structural damage in rheumatoid arthritis. Libyan J Med. 2018;13:1512330.
   PubMed Web of Science ®Google Scholar
• Hashimoto J, Garnero P, Van Der Heijde D, et al. A combination of biochemical markers of cartilage and bone turnover, radiographic damage and body mass index to predict the progression of joint destruction in patients with rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs. Mod Rheumatol. 2009;19:273–282.
   PubMed Web of Science ®Google Scholar
• Garnero P, Thompson E, Woodworth T, et al. Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of th. Arthritis Rheum. 2010;62:33–43.
   PubMed Web of Science ®Google Scholar
• Niki Y, Takeuchi T, Nakayama M, et al. Clinical significance of cartilage biomarkers for monitoring structural joint damage in rheumatoid arthritis patients treated with anti-TNF therapy. PLoS One. 2012;7:e37447.
   PubMed Web of Science ®Google Scholar
• Verstappen SMM, Poole AR, Ionescu M, et al. Radiographic joint damage in rheumatoid arthritis is associated with differences in cartilage turnover and can be predicted by serum biomarkers: an evaluation from 1 to 4 years after diagnosis. Arthritis Res Ther. 2006;8:R31.
   PubMed Web of Science ®Google Scholar
• Connolly M, Mullan RH, McCormick J, et al. Acute-phase serum amyloid A regulates tumor necrosis factor α and matrix turnover and predicts disease progression in patients with inflammatory arthritis before and after biologic therapy. Arthritis Rheum. 2012;64:1035–1045.
   PubMed Web of Science ®Google Scholar
• Lindqvist E, Eberhardt K, Bendtzen K, et al. Prognostic laboratory markers of joint damage in rheumatoid arthritis. Ann Rheum Dis. 2005;64:196–201.
   PubMed Web of Science ®Google Scholar
• Szeremeta A, Jura-Półtorak A, Koźma EM, et al. Effects of a 15-month anti-TNF-α treatment on plasma levels of glycosaminoglycans in women with rheumatoid arthritis 11 Medical and Health Sciences 1103 Clinical Sciences. Arthritis Res Ther. 2018;20:211.
   PubMedGoogle Scholar
• Syversen SW, Goll GL, Van Der Heijde D, et al. Cartilage and bone biomarkers in rheumatoid arthritis: prediction of 10-year radiographic progression. J Rheumatol. 2009;36:266–272.
   PubMed Web of Science ®Google Scholar
• Syversen SW, Goll GL, Van Der Heijde D, et al. 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. 2010;69:345–351.
   PubMed Web of Science ®Google Scholar
• Gudmann NS, Hirata S, Karsdal MA, et al. Increased remodelling of interstitial collagens and basement membrane is suppressed by treatment in patients with rheumatoid arthritis: serological evaluation of a one-year prospective study of 149 Japanese patients. Clin Exp Rheumatol. 2018;36:462–470.
   PubMed Web of Science ®Google Scholar
• Bay-Jensen AC, Platt A, Jenkins MA, et al. Tissue metabolite of type I collagen, C1M, and CRP predicts structural progression of rheumatoid arthritis. BMC Rheumatol. 2019;3:3.
   PubMedGoogle Scholar
• Gudmann NS, Junker P, Juhl P, et al. Type IV collagen metabolism is associated with disease activity, radiographic progression and response to tocilizumab in rheumatoid arthritis. Clin Exp Rheumatol. 2018;36:829–835.
   PubMed Web of Science ®Google Scholar
• Juhl P, Thudium CS, Gudmann NS, et al. IL-6 receptor inhibition modulates type III collagen and C-reactive protein degradation in rheumatoid arthritis patients with an inadequate response to anti-tumour necrosis factor therapy: analysis of connective tissue turnover in the tocilizumab RADIATE. Clin Exp Rheumatol. 2018;36:568–574.
   PubMed Web of Science ®Google Scholar
• Kjelgaard-Petersen CF, Platt A, Braddock M, et al. Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis. Arthritis Rheumatol. 2018;70:1419–1428.
   PubMed Web of Science ®Google Scholar
• Gabay C, Msihid J, Zilberstein M, et al. Identification of sarilumab pharmacodynamic and predictive markers in patients with inadequate response to TNF inhibition: a biomarker substudy of the phase 3 TARGET study. RMD Open. 2018;4:e000607.
   PubMed Web of Science ®Google Scholar
• Chopin F, Garnero P, Le Henanff A, et al. Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67:353-357.
   PubMedGoogle Scholar
• Karsdal MA, Schett G, Emery P, et al. IL-6 Receptor Inhibition Positively Modulates Bone Balance in Rheumatoid Arthritis Patients with an Inadequate Response to Anti-Tumor Necrosis Factor Therapy: biochemical Marker Analysis of Bone Metabolism in the Tocilizumab RADIATE Study (NCT00106522). Semin Arthritis Rheum. 2012;42:131–139.
   PubMed Web of Science ®Google Scholar
• Thudium CS, Bay-Jensen AC, Cahya S, et al. The Janus kinase 1/2 inhibitor baricitinib reduces biomarkers of joint destruction in moderate to severe rheumatoid arthritis. Arthritis Res Ther. 2020;22:235.
   PubMed Web of Science ®Google Scholar
• Abu Al Fadl EM, Fattouh M, Allam AA. High IL-. 23 level is a marker of disease activity in rheumatoid arthritis. Egypt J Immunol. 2013;20:85–92.
   PubMedGoogle Scholar
• Park MC, Jung SJ, Park YB, et al. Relationship of serum TWEAK level to cytokine level, disease activity, and response to anti-TNF treatment in patients with rheumatoid arthritis. Scand J Rheumatol. 2008;37:173–178.
   PubMed Web of Science ®Google Scholar
• Song L, Wang Y, Sui Y, et al. High interleukin-37 (IL-37) expression and increased mucin-domain containing-3 (TIM-3) on peripheral T cells in patients with rheumatoid arthritis. Med Sci Monit. 2018;24:5660–5667.
   PubMed Web of Science ®Google Scholar
• Petrovic-Rackov L. Cytokines in rheumatoid arthritis and osteoarthrosis. Med Pregl. 2005;58:245–251.
   PubMedGoogle Scholar
• Koca SS, Isik A, Ustundag B, et al. Serum pro-hepcidin levels in rheumatoid arthritis and systemic lupus erythematosus. Inflammation. 2008;31:146–153.
   PubMed Web of Science ®Google Scholar
• Kobayashi T, Yokoyama T, Ishida K, et al. Serum Cytokine and Periodontal Profiles in Relation to Disease Activity of Rheumatoid Arthritis in Japanese Adults. J Periodontol. 2010;81:650–657.
   PubMed Web of Science ®Google Scholar
• Uno K, Yoshizaki K, Iwahashi M, et al. Pretreatment prediction of individual rheumatoid arthritis patients’ response to anti-cytokine therapy using serum cytokine/chemokine/soluble receptor biomarkers. PLoS One. 2015;10:1–15.
   Web of Science ®Google Scholar
• Ramírez J, Inciarte-Mundo J, Cuervo A, et al. Differing local and systemic inflammatory burden in polyarticular psoriatic arthritis and rheumatoid arthritis patients on anti-TNF treatment in clinical remission. Clin Exp Rheumatol. 2017;35:74–79.
   PubMed Web of Science ®Google Scholar
• Guo Q, Wang Y, Xu D, et al. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018;6:15.
   Web of Science ®Google Scholar
• Blaess J, Walther J, Petitdemange A, et al. Immunosuppressive agents for rheumatoid arthritis: a systematic review of clinical trials and their current development stage. Ther Adv Musculoskelet Dis. 2020;12:1–12.
   Web of Science ®Google Scholar
• Srirangan S, Choy EH. The role of Interleukin 6 in the pathophysiology of rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2010;2:247–256.
   PubMedGoogle Scholar
• Chung SJ, Kwon YJ, Park MC, et al. The correlation between increased serum concentrations of interleukin-6 family cytokines and disease activity in rheumatoid arthritis patients. Yonsei Med J. 2011;52:113–120.
   PubMed Web of Science ®Google Scholar
• Tekeoğlu İ, Harman H, Sağ S, et al. Levels of serum pentraxin 3, IL-6, fetuin A and insulin in patients with rheumatoid arthritis. Cytokine. 2016;83:171–175.
   PubMed Web of Science ®Google Scholar
• Gabay C. Interleukin- 6 and chronic inflammation. Arthritis Res Ther. 2006;8:S3.
   PubMed Web of Science ®Google Scholar
• Chen DY, Hsieh TY, Chen YM, et al. Proinflammatory cytokine profiles of patients with elderly-onset rheumatoid arthritis: a comparison with younger-onset disease. Gerontology. 2009;55:250–258.
   PubMed Web of Science ®Google Scholar
• Hueber W, Tomooka BH, Zhao X, et al. Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti-citrulline autoreactivity is associated with up regulation of proinflammatory cytokines. Ann Rheum Dis. 2007;66:712–719.
   PubMed Web of Science ®Google Scholar
• Cad DL, Rushansky E, Adelino JE, et al. Are key cytokines genetic and serum levels variations related to rheumatoid arthritis clinical severity? Gene. 2020;722:144098.
   PubMed Web of Science ®Google Scholar
• Gonzalez-Orozco M, Barbosa-Cobos RE, Santana-Sanchez P, et al. Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis. Allergy Asthma Clin Immunol. 2019;15:1–11.
   PubMed Web of Science ®Google Scholar
• Šenolt L, Prajzlerová K, Hulejová H, et al. Interleukin-20 is triggered by TLR ligands and associates with disease activity in patients with rheumatoid arthritis. Cytokine. 2017;97:187–192.
   PubMed Web of Science ®Google Scholar
• Liu R, Wu Q, Su D, et al. A regulatory effect of IL-21 on T follicular helper-like cell and B cell in rheumatoid arthritis. Arthritis Res Ther. 2012;14:R255.
   PubMed Web of Science ®Google Scholar
• Wang F, Xu L, Feng X, et al. Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis. Arthritis Res Ther. 2012;14:R228.
   PubMed Web of Science ®Google Scholar
• Chang QJ, Lv C, Zhao F, et al. Elevated serum levels of interleukin-29 are associated with disease activity in rheumatoid arthritis patients with anti-cyclic citrullinated peptide antibodies. Tohoku J Exp Med. 2017;241:89–95.
   PubMed Web of Science ®Google Scholar
• Chang SH, Choi BY, Choi J, et al. Baseline serum interleukin-34 levels independently predict radiographic progression in patients with rheumatoid arthritis. Rheumatol Int. 2015;35:71–79.
   PubMed Web of Science ®Google Scholar
• Tian Y, Shen H, Xia L, et al. Elevated serum and synovial fluid levels of interleukin-34 in rheumatoid arthritis: possible association with disease progression via interleukin-17 production. J Interf Cytokine Res. 2013;33:398–401.
   PubMed Web of Science ®Google Scholar
• Zhang XIA, Zhang X, Zhuang L, et al. Decreased regulatory t-cell frequency and interleukin-3levels in patients with rheumatoid arthritis. Exp Ther Med. 2018;16:5366–5372.
   PubMed Web of Science ®Google Scholar
• Li Y, Yao L, Liu S, et al. Elevated serum IL-35 levels in rheumatoid arthritis are associated with disease activity. J Investig Med. 2019;67:707–710.
   PubMed Web of Science ®Google Scholar
• Ragab D, Mobasher S, Shabaan E. Elevated levels of IL-37 correlate with T cell activation status in rheumatoid arthritis patients. Cytokine. 2019;113:305–310.
   PubMed Web of Science ®Google Scholar
• Shindo E, Nanki T, Kusunoki N, et al. The growth factor midkine may play a pathophysiological role in rheumatoid arthritis. Mod Rheumatol. 2017;27:54–59.
   PubMed Web of Science ®Google Scholar
• Llamas-Covarrubias MA, Valle Y, Navarro-Hernández RE, et al. Serum levels of macrophage migration inhibitory factor are associated with rheumatoid arthritis course. Rheumatol Int. 2012;32:2307–2311.
   PubMed Web of Science ®Google Scholar
• Wijbrandts CA, Van Leuven SI, Boom HD, et al. Sustained changes in lipid profile and macrophage migration inhibitory factor levels after anti-tumour necrosis factor therapy in rheumatoid arthritis. Ann Rheum Dis. 2009;68:1316–1321.
   PubMed Web of Science ®Google Scholar
• Sims JE, Smith DE, The IL. 1 family: regulators of immunity. Nat Rev Immunol. 2010;10:89–102.
   PubMed Web of Science ®Google Scholar
• Danis VA, Franic GM, Rathjen DA, et al. Circulating cytokine levels in patients with rheumatoid arthritis: results of a double blind trial with sulphasalazine. Ann Rheum Dis. 1992;51:946–950.
   PubMed Web of Science ®Google Scholar
• Saǧ S, Saǧ MS, Tekeoǧlu I, et al. Relationship of hematologic markers with IL-17 and IL-1 beta in patients with rheumatoid arthritis. J Back Musculoskelet Rehabil. 2018;31:703–707.
   PubMed Web of Science ®Google Scholar
• Bresnihan B, Alvaro-Gracia JM, Cobby M, et al. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum. 1998;41:2196–2204.
   PubMed Web of Science ®Google Scholar
• Thaler K, Chandiramani HR. Efficacy and safety of anakinra for the treatment of rheumatoid arthritis: an update of the Oregon Drug  Effectiveness Review Project. Biol Targets Ther. 2009;3:485.
   PubMedGoogle Scholar
• Sellam J, Rivière E, Courties A, et al. Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis. Arthritis Res Ther. 2016;18:294.
   PubMed Web of Science ®Google Scholar
• Talabot-Ayer D, McKee T, Gindre P, et al. Distinct serum and synovial fluid interleukin (IL)-33 levels in rheumatoid arthritis, psoriatic arthritis and osteoarthritis. Jt Bone Spine. 2012;79:32–37.
   PubMed Web of Science ®Google Scholar
• Tang S, Huang H, Hu F, et al. Increased IL-33 in synovial fluid and paired serum is associated with disease activity and autoantibodies in rheumatoid arthritis. Clin Dev Immunol. 2013;2013:985301.
   PubMedGoogle Scholar
• Xiangyang Z, Lutian Y, Lin Z, et al. Increased levels of interleukin-33 associated with bone erosion and interstitial lung diseases in patients with rheumatoid arthritis. Cytokine. 2012;58:6–9.
   PubMed Web of Science ®Google Scholar
• Le Goff B, Bouvard B, Lequerre T, et al. Implication of IL-17 in Bone Loss and Structural Damage in Inflammatory Rheumatic Diseases. Mediators Inflamm. 2019;2019:8659302.
   PubMed Web of Science ®Google Scholar
• Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol. 2009;9:556–567.
   PubMed Web of Science ®Google Scholar
• Dubin PJ, Kolls JK. Interleukin-17A and Interleukin-17F: a Tale of Two Cytokines. Immunity. 2009;30:9–11.
   PubMed Web of Science ®Google Scholar
• Akimzhanov AM, Yang XO, Dong C. Chromatin remodeling of interleukin-17 (IL-17)-IL-17F cytokine gene locus during inflammatory helper T cell differentiation. J Biol Chem. 2007;282:5969–5972.
   PubMed Web of Science ®Google Scholar
• Dhaouadi T, Chahbi M, Haouami Y, et al. IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis. Zhou X, Editor PLoS One. 2018;13:e0194883.
   PubMed Web of Science ®Google Scholar
• Park JS, Park MK, Lee SY, et al. TWEAK promotes the production of Interleukin-17 in rheumatoid arthritis. Cytokine. 2012;60:143–149.
   PubMed Web of Science ®Google Scholar
• Al-Saadany HM, Hussein MS, Gaber RA, et al. Th-17 cells and serum IL-17 in rheumatoid arthritis patients: correlation with disease activity and severity. Egypt Rheumatol. 2016;38:1–7.
   Web of Science ®Google Scholar
• Dougados M. Treat to target in axial spondyloarthritis: from its concept to its implementation. J Autoimmun. 2020;110:102398.
   PubMed Web of Science ®Google Scholar
• Brennan FM, McInnes IB. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest. 2008;118:3537–45.
   PubMed Web of Science ®Google Scholar
• Zaky DSE, El-Nahrery EMA. Role of interleukin-23 as a biomarker in rheumatoid arthritis patients and its correlation with disease activity. Int Immunopharmacol. 2016;31:105–108.
   PubMed Web of Science ®Google Scholar
• Guo YY, Wang NZ, Zhao S, et al. Increased interleukin-23 is associated with increased disease activity in patients with rheumatoid arthritis. Chin Med J (Engl). 2013;126:850–854.
   PubMed Web of Science ®Google Scholar
• Zivojinovic SM, Pejnovic NN, Sefik-Bukilica MN, et al. Tumor necrosis factor blockade differentially affects innate inflammatory and Th17 cytokines in rheumatoid arthritis. J Rheumatol. 2012;39:18–21.
   PubMed Web of Science ®Google Scholar
• Kim J, Kang S, Kim J, et al. Elevated levels of T helper 17 cells are associated with disease activity in patients with rheumatoid arthritis. Ann Lab Med. 2013;33:52–59.
   PubMed Web of Science ®Google Scholar
• Smolen JS, Agarwal SK, Ilivanova E, et al. A randomised phase II study evaluating the efficacy and safety of subcutaneously administered ustekinumab and guselkumab in patients with active rheumatoid arthritis despite treatment with methotrexate. Ann Rheum Dis. 2017;76:831–839.
   PubMed Web of Science ®Google Scholar
• Centola M, Cavet G, Shen Y, et al. Development of a Multi-Biomarker Disease Activity Test for Rheumatoid Arthritis. PLoS One. 2013;118:3537–45.
   PubMed Web of Science ®Google Scholar
• Eastman PS, Manning WC, Qureshi F, et al. Characterization of a multiplex, 12-biomarker test for rheumatoid arthritis. J Pharm Biomed Anal. 2012;70:415–24.
   PubMed Web of Science ®Google Scholar
• Johnson TM, Register KA, Schmidt CM, et al. Correlation of the Multi-Biomarker Disease Activity Score With Rheumatoid Arthritis Disease Activity Measures: a Systematic Review and Meta-Analysis. Arthritis Care Res. 2019;71:1459–1472.
   PubMed Web of Science ®Google Scholar
• Lourido L, Blanco FJ, Ruiz-Romero C. Defining the proteomic landscape of rheumatoid arthritis: progress and prospective clinical applications. Expert Rev Proteomics. 2017;14:431–444.
   PubMed Web of Science ®Google Scholar
• Márquez A, Martín J, Carmona FD. Emerging aspects of molecular biomarkers for diagnosis, prognosis and treatment response in rheumatoid arthritis. Expert Rev Mol Diagn. 2016;16:663–673.
   PubMed Web of Science ®Google Scholar
• Ourradi K, Sharif M. Opportunities and challenges for the discovery and validation of proteomic biomarkers for common arthritic diseases. Biomark Med. 2017;11:877–892.
   PubMed Web of Science ®Google Scholar
• Song X, Lin Q. Genomics, transcriptomics and proteomics to elucidate the pathogenesis of rheumatoid arthritis. Rheumatol Int. 2017;37:1257–1265.
   PubMed Web of Science ®Google Scholar
• FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools). Updat. Sept. 25. Food and Drug Administration (US); 2017.
   Google Scholar
• Ospelt C, Bang H, Feist E, et al. Carbamylation of vimentin is inducible by smoking and represents an independent autoantigen in rheumatoid arthritis. Ann Rheum Dis. 2017;76:1176–1183.
   PubMed Web of Science ®Google Scholar
• Ishikawa Y, Ikari K, Hashimoto M, et al. Shared epitope defines distinct associations of cigarette smoking with levels of anticitrullinated protein antibody and rheumatoid factor. Ann Rheum Dis. 2019;78:1480–1487.
   PubMed Web of Science ®Google Scholar
• Dennis G, Holweg CTJ, Kummerfeld SK, et al. Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics. Arthritis Res Ther. 2014;16:R90.
   PubMed Web of Science ®Google Scholar
• Humby F, Lewis M, Ramamoorthi N, et al. Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients. Ann Rheum Dis. 2019;78:761–772.
   PubMed Web of Science ®Google Scholar
• Seegobin SD, Ma MHY, Dahanayake C, et al. ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and corticosteroids: secondary analysis of a randomized controlled trial. Arthritis Res Ther. 2014;16:R13.
   PubMed Web of Science ®Google Scholar