{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T22:26:16Z","timestamp":1783117576567,"version":"3.54.6"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Med"],"published-print":{"date-parts":[[2022,2]]},"DOI":"10.1007\/s10238-021-00725-9","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T17:10:49Z","timestamp":1622135449000},"page":"37-45","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["TGFB1 (rs1800470 and rs1800469) variants are independently associated with disease activity and autoantibodies in rheumatoid arthritis patients"],"prefix":"10.1007","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0801-3098","authenticated-orcid":false,"given":"Tatiana Mayumi Veiga","family":"Iriyoda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamires","family":"Flauzino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neide Tomimura","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcell Alysson Batisti","family":"Lozovoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna Maria Vissoci","family":"Reiche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9a Name Colado","family":"Sim\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"725_CR1","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.cca.2016.02.010","volume":"455","author":"S Mateen","year":"2016","unstructured":"Mateen S, Zafar A, Moin S, Khan AQ, Zubair S. Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis. Clin Chim Acta. 2016;455:161\u201371.","journal-title":"Clin Chim Acta"},{"issue":"1","key":"725_CR2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41413-018-0016-9","volume":"6","author":"Q Guo","year":"2018","unstructured":"Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018;6(1):15.","journal-title":"Bone Res"},{"issue":"1","key":"725_CR3","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/nri.2016.124","volume":"17","author":"V Malmstr\u00f6m","year":"2017","unstructured":"Malmstr\u00f6m V, Catrina AI, Klareskog L. The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting. Nat Rev Immunol. 2017;17(1):60\u201375.","journal-title":"Nat Rev Immunol"},{"issue":"6","key":"725_CR4","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1155\/2013\/726598","volume":"35","author":"F Ingegnoli","year":"2013","unstructured":"Ingegnoli F, Castelli R, Gualtierotti R. Rheumatoid factors: clinical applications. Dis Markers. 2013;35(6):727\u201334.","journal-title":"Dis Markers"},{"issue":"10","key":"725_CR5","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.1002\/art.11223","volume":"48","author":"S Rantap\u00e4\u00e4-Dahlqvist","year":"2003","unstructured":"Rantap\u00e4\u00e4-Dahlqvist S, de Jong BAW, Berglin E, et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003;48(10):2741\u20139.","journal-title":"Arthritis Rheum"},{"issue":"1","key":"725_CR6","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1002\/art.30081","volume":"63","author":"J Sokolove","year":"2011","unstructured":"Sokolove J, Zhao X, Chandra PE, Robinson WH. Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fc\u03b3 receptor. Arthritis Rheum. 2011;63(1):53\u201362.","journal-title":"Arthritis Rheum"},{"issue":"9","key":"725_CR7","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1007\/s00296-011-1984-x","volume":"32","author":"Q Niu","year":"2012","unstructured":"Niu Q, Cai B, Huang Z, Shi Y, Wang L. Disturbed Th17\/Treg balance in patients with rheumatoid arthritis. Rheumatol Int. 2012;32(9):2731\u20136.","journal-title":"Rheumatol Int"},{"issue":"1","key":"725_CR8","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s10238-018-0530-5","volume":"19","author":"X Wang","year":"2019","unstructured":"Wang X, Yang C, Xu F, Qi L, Wang J, Yang P. Imbalance of circulating Tfr\/Tfh ratio in patients with rheumatoid arthritis. Clin Exp Med. 2019;19(1):55\u201364.","journal-title":"Clin Exp Med"},{"issue":"4","key":"725_CR9","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/ni1178","volume":"6","author":"S Sakaguchi","year":"2005","unstructured":"Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol. 2005;6(4):345\u201352.","journal-title":"Nat Immunol"},{"issue":"4","key":"725_CR10","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.4049\/jimmunol.178.4.2018","volume":"178","author":"SG Zheng","year":"2007","unstructured":"Zheng SG, Wang J, Wang P, Gray JD, Horwitz DA. IL-2 Is essential for TGF-\u03b2 to convert naive CD4 + CD25 \u2212 Cells to CD25 + Foxp3 + regulatory T CELLS AND FOR EXPANSION OF THESE CELLS. J Immunol. 2007;178(4):2018\u201327.","journal-title":"J Immunol"},{"issue":"1","key":"725_CR11","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev.immunol.24.021605.090737","volume":"24","author":"MO Li","year":"2006","unstructured":"Li MO, Wan YY, Sanjabi S, Robertson A-KL, Flavell RA. Transforming growth factor-\u03b2 regulation of immune responses. Annu Rev Immunol. 2006;24(1):99\u2013146.","journal-title":"Annu Rev Immunol"},{"issue":"4","key":"725_CR12","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1111\/j.1744-313X.2010.00913.x","volume":"37","author":"A Paradowska-Gorycka","year":"2010","unstructured":"Paradowska-Gorycka A, Trefler J, Maciejewska-Stelmach J, \u0141\u0105cki JK. Interleukin-10 gene promoter polymorphism in Polish rheumatoid arthritis patients. Int J Immunogenet. 2010;37(4):225\u201331.","journal-title":"Int J Immunogenet"},{"issue":"3","key":"725_CR13","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s10238-019-00556-9","volume":"19","author":"FA de Medeiros","year":"2019","unstructured":"de Medeiros FA, Alfieri DF, Iriyoda TMV, et al. TNF-\u03b2 +252 A>G (rs909253) polymorphism is independently associated with presence of autoantibodies in rheumatoid arthritis patients. Clin Exp Med. 2019;19(3):347\u201356.","journal-title":"Clin Exp Med"},{"issue":"6","key":"725_CR14","doi-asserted-by":"publisher","first-page":"469","DOI":"10.3109\/10799893.2014.919594","volume":"34","author":"T-B Zhou","year":"2014","unstructured":"Zhou T-B, Zhao H-L, Fang S-L, Drummen GPC. Association of transforming growth factor-\u03b21 T869C, G915C, and C509T gene polymorphisms with rheumatoid arthritis risk. J Recept Signal Transduct. 2014;34(6):469\u201375.","journal-title":"J Recept Signal Transduct"},{"issue":"1","key":"725_CR15","doi-asserted-by":"publisher","first-page":"53","DOI":"10.14715\/cmb\/2017.63.1.11","volume":"63","author":"YH Lee","year":"2017","unstructured":"Lee YH, Bae S-C. Association between circulating transforming growth factor-\u03b21 level and polymorphisms in systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis. Cell Mol Biol (Noisy-le-grand). 2017;63(1):53\u20139.","journal-title":"Cell Mol Biol (Noisy-le-grand)"},{"issue":"2","key":"725_CR16","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1002\/1529-0131(200002)43:2<452::AID-ANR28>3.0.CO;2-C","volume":"43","author":"Y Yamada","year":"2000","unstructured":"Yamada Y, Okuizumi H, Miyauchi A, Takagi Y, Ikeda K, Harada A. Association of transforming growth factor \u03b21 genotype with spinal osteophytosis in Japanese women. Arthritis Rheum. 2000;43(2):452.","journal-title":"Arthritis Rheum"},{"issue":"2","key":"725_CR17","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.gene.2013.11.042","volume":"536","author":"YM Hussein","year":"2014","unstructured":"Hussein YM, Mohamed RH, El-Shahawy EE, Alzahrani SS. Interaction between TGF-\u03b21 (869C\/T) polymorphism and biochemical risk factor for prediction of disease progression in rheumatoid arthritis. Gene. 2014;536(2):393\u20137.","journal-title":"Gene"},{"issue":"1\u20132","key":"725_CR18","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s00439-005-0112-y","volume":"119","author":"R Shah","year":"2006","unstructured":"Shah R, Rahaman B, Hurley CK, Posch PE. Allelic diversity in the TGFB1 regulatory region: characterization of novel functional single nucleotide polymorphisms. Hum Genet. 2006;119(1\u20132):61\u201374.","journal-title":"Hum Genet"},{"key":"725_CR19","doi-asserted-by":"crossref","unstructured":"Cao H, Zhou Q, Lan R, et al. A Functional Polymorphism C-509T in TGF\u03b2-1 Promoter Contributes to Susceptibility and Prognosis of Lone Atrial Fibrillation in Chinese Population. Jeyaseelan K, ed. PLoS One. 2014; 9(11):e112912.","DOI":"10.1371\/journal.pone.0112912"},{"issue":"3","key":"725_CR20","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1111\/j.1744-313X.2010.00991.x","volume":"38","author":"W Guo","year":"2011","unstructured":"Guo W, Dong Z, Guo Y, et al. Polymorphisms of transforming growth factor-\u03b21 associated with increased risk of gastric cardia adenocarcinoma in north China. Int J Immunogenet. 2011;38(3):215\u201324.","journal-title":"Int J Immunogenet"},{"issue":"9","key":"725_CR21","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1002\/art.27584","volume":"62","author":"D Aletaha","year":"2010","unstructured":"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(9):2569\u201381.","journal-title":"Arthritis Rheum"},{"issue":"5","key":"725_CR22","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1002\/acr.21649","volume":"64","author":"J Anderson","year":"2012","unstructured":"Anderson J, Caplan L, Yazdany J, et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken). 2012;64(5):640\u20137.","journal-title":"Arthritis Care Res (Hoboken)"},{"issue":"15","key":"725_CR23","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.1093\/bioinformatics\/btl268","volume":"22","author":"X Sole","year":"2006","unstructured":"Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22(15):1928\u20139.","journal-title":"Bioinformatics"},{"issue":"12","key":"725_CR24","doi-asserted-by":"publisher","first-page":"2502","DOI":"10.3899\/jrheum.100324","volume":"37","author":"B de Paz","year":"2010","unstructured":"de Paz B, Alperi-L\u00f3pez M, Ballina-Garc\u00eda FJ, Prado C, Guti\u00e9rrez C, Su\u00e1rez A. Cytokines and regulatory T cells in rheumatoid arthritis and their relationship with response to corticosteroids. J Rheumatol. 2010;37(12):2502\u201310.","journal-title":"J Rheumatol"},{"key":"725_CR25","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.imlet.2018.10.001","volume":"204","author":"V Hashemi","year":"2018","unstructured":"Hashemi V, Farrokhi AS, Tanomand A, et al. Polymorphism of Foxp3 gene affects the frequency of regulatory T cells and disease activity in patients with rheumatoid arthritis in Iranian population. Immunol Lett. 2018;204:16\u201322.","journal-title":"Immunol Lett"},{"issue":"6","key":"725_CR26","doi-asserted-by":"publisher","first-page":"a022236","DOI":"10.1101\/cshperspect.a022236","volume":"9","author":"S Sanjabi","year":"2017","unstructured":"Sanjabi S, Oh SA, Li MO. Regulation of the immune response by TGF-\u03b2: from conception to autoimmunity and infection. Cold Spring Harb Perspect Biol. 2017;9(6):a022236.","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"5","key":"725_CR27","doi-asserted-by":"publisher","first-page":"370","DOI":"10.3109\/03008200903461462","volume":"51","author":"D-Y Chen","year":"2010","unstructured":"Chen D-Y, Chen Y-M, Chen H-H, Hsieh C-W, Lin C, Lan J-L. The associations of circulating CD4 + CD25 high regulatory T cells and TGF-\u03b2 with disease activity and clinical course in patients with adult-onset Still\u2019s disease. Connect Tissue Res. 2010;51(5):370\u20137.","journal-title":"Connect Tissue Res"},{"issue":"3","key":"725_CR28","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1177\/0961203311425528","volume":"21","author":"T Jin","year":"2012","unstructured":"Jin T, Almehed K, Carlsten H, Forsblad-d\u2019Elia H. Decreased serum levels of TGF-\u03b21 are associated with renal damage in female patients with systemic lupus erythematosus. Lupus. 2012;21(3):310\u20138.","journal-title":"Lupus"},{"issue":"8","key":"725_CR29","doi-asserted-by":"publisher","first-page":"4811","DOI":"10.1007\/s11033-013-2577-4","volume":"40","author":"L Zhang","year":"2013","unstructured":"Zhang L, Yan J, Wang Y-X, et al. Association of TGF-\u03b21 +869C\/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis. Mol Biol Rep. 2013;40(8):4811\u20137.","journal-title":"Mol Biol Rep"},{"issue":"5","key":"725_CR30","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1902\/jop.2009.080573","volume":"80","author":"T Kobayashi","year":"2009","unstructured":"Kobayashi T, Murasawa A, Ito S, et al. Cytokine gene polymorphisms associated with rheumatoid arthritis and periodontitis in Japanese adults. J Periodontol. 2009;80(5):792\u20139.","journal-title":"J Periodontol"},{"issue":"1","key":"725_CR31","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.jbspin.2008.02.012","volume":"76","author":"G Alayli","year":"2009","unstructured":"Alayli G, Kara N, Tander B, Canturk F, Gunes S, Bagci H. Association of transforming growth factor \u03b21 gene polymorphism with rheumatoid arthritis in a Turkish population. Jt Bone Spine. 2009;76(1):20\u20133.","journal-title":"Jt Bone Spine"},{"issue":"2","key":"725_CR32","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1093\/rheumatology\/ken443","volume":"48","author":"VF Panoulas","year":"2008","unstructured":"Panoulas VF, Douglas KMJ, Smith JP, et al. Transforming growth factor- 1 869T\/C, but not interleukin-6 -174G\/C, polymorphism associates with hypertension in rheumatoid arthritis. Rheumatology. 2008;48(2):113\u20138.","journal-title":"Rheumatology"},{"issue":"9","key":"725_CR33","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1136\/ard.62.9.907","volume":"62","author":"V Pokorny","year":"2003","unstructured":"Pokorny V. Transforming growth factor 1 gene (HSTGFB1) nucleotide T869C (codon 10) polymorphism is not associated with prevalence or severity of rheumatoid arthritis in a Caucasian population. Ann Rheum Dis. 2003;62(9):907\u20138.","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"725_CR34","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1080\/03009740410010344","volume":"33","author":"S Kim","year":"2004","unstructured":"Kim S, Han S, Kim G, Lee J, Kang Y. TGF-\u00df1 polymorphism determines the progression of joint damage in rheumatoid arthritis. Scand J Rheumatol. 2004;33(6):389\u201394.","journal-title":"Scand J Rheumatol"},{"issue":"10","key":"725_CR35","doi-asserted-by":"publisher","first-page":"2881","DOI":"10.1007\/s10067-020-05064-w","volume":"39","author":"SL Patel","year":"2020","unstructured":"Patel SL, Prakash J, Gupta V. TGF-\u03b21 +869C\/T polymorphism increases susceptibility to rheumatoid arthritis in North Indian population. Clin Rheumatol. 2020;39(10):2881\u20138.","journal-title":"Clin Rheumatol"},{"issue":"9","key":"725_CR36","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1136\/ard.61.9.826","volume":"61","author":"Y Sugiura","year":"2002","unstructured":"Sugiura Y. Transforming growth factor beta1 gene polymorphism in rheumatoid arthritis. Ann Rheum Dis. 2002;61(9):826\u20138.","journal-title":"Ann Rheum Dis"},{"key":"725_CR37","doi-asserted-by":"crossref","unstructured":"Saad MN, Mabrouk MS, Eldeib AM, Shaker OG. Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis. Garcia de Frutos P, ed. PLoS One. 2015; 10(7):e0131960.","DOI":"10.1371\/journal.pone.0131960"},{"issue":"1","key":"725_CR38","first-page":"127","volume":"19","author":"W Sun","year":"2019","unstructured":"Sun W, Yi M, Bai Y, et al. Correlations between the polymorphism of +869T\/C in TGF-\u03b21 and rheumatoid arthritis. J Musculoskelet Neuronal Interact. 2019;19(1):127\u201332.","journal-title":"J Musculoskelet Neuronal Interact"},{"issue":"6","key":"725_CR39","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nrrheum.2015.7","volume":"11","author":"K Yamamoto","year":"2015","unstructured":"Yamamoto K, Okada Y, Suzuki A, Kochi Y. Genetics of rheumatoid arthritis in Asia\u2013present and future. Nat Rev Rheumatol. 2015;11(6):375\u20139.","journal-title":"Nat Rev Rheumatol"},{"issue":"4","key":"725_CR40","doi-asserted-by":"publisher","first-page":"R111","DOI":"10.1186\/ar3396","volume":"13","author":"F Ceccarelli","year":"2011","unstructured":"Ceccarelli F, Perricone C, Fabris M, et al. Transforming growth factor \u03b2 869C\/T and interleukin 6\u2013174G\/C polymorphisms relate to the severity and progression of bone-erosive damage detected by ultrasound in rheumatoid arthritis. Arthritis Res Ther. 2011;13(4):R111.","journal-title":"Arthritis Res Ther"},{"issue":"5","key":"725_CR41","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.jbspin.2019.01.005","volume":"86","author":"F Coutant","year":"2019","unstructured":"Coutant F. Pathogenic effects of anti-citrullinated protein antibodies in rheumatoid arthritis \u2013 role for glycosylation. Jt Bone Spine. 2019;86(5):562\u20137.","journal-title":"Jt Bone Spine"},{"issue":"6","key":"725_CR42","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1002\/art.27414","volume":"62","author":"HU Scherer","year":"2010","unstructured":"Scherer HU, van der Woude D, Ioan-Facsinay A, et al. Glycan profiling of anti-citrullinated protein antibodies isolated from human serum and synovial fluid. Arthritis Rheum. 2010;62(6):1620\u20139.","journal-title":"Arthritis Rheum"},{"issue":"1","key":"725_CR43","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1002\/1529-0131(200101)44:1<41::AID-ANR6>3.0.CO;2-0","volume":"44","author":"CC Reparon-Schuijt","year":"2001","unstructured":"Reparon-Schuijt CC, van Esch WJE, van Kooten C, et al. Secretion of anti-citrulline-containing peptide antibody by B lymphocytes in rheumatoid arthritis. Arthritis Rheum. 2001;44(1):41\u20137.","journal-title":"Arthritis Rheum"},{"issue":"6","key":"725_CR44","first-page":"1002","volume":"35","author":"L Innala","year":"2008","unstructured":"Innala L, Kokkonen H, Eriksson C, Jidell E, Berglin E, Dahlqvst SR. Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides. J Rheumatol. 2008;35(6):1002\u20138.","journal-title":"J Rheumatol"},{"issue":"2","key":"725_CR45","doi-asserted-by":"publisher","first-page":"R81","DOI":"10.1186\/ar3804","volume":"14","author":"Y Chen","year":"2012","unstructured":"Chen Y, Dawes PT, Packham JC, Mattey DL. Interaction between smoking and functional polymorphism in the TGFB1 gene is associated with ischaemic heart disease and myocardial infarction in patients with rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther. 2012;14(2):R81.","journal-title":"Arthritis Res Ther"},{"issue":"7","key":"725_CR46","doi-asserted-by":"publisher","first-page":"2082","DOI":"10.1002\/art.20350","volume":"50","author":"PMJ Welsing","year":"2004","unstructured":"Welsing PMJ, Landew\u00e9 RBM, Van Riel PLCM, et al. The relationship between disease activity and radiologic progression in patients with rheumatoid arthritis: a longitudinal analysis. Arthritis Rheum. 2004;50(7):2082\u201393.","journal-title":"Arthritis Rheum"},{"issue":"1","key":"725_CR47","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1136\/annrheumdis-2011-201247","volume":"72","author":"A Kavanaugh","year":"2013","unstructured":"Kavanaugh A, Fleischmann RM, Emery P, et al. Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study. Ann Rheum Dis. 2013;72(1):64\u201371.","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"725_CR48","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1002\/art.21678","volume":"54","author":"JS Smolen","year":"2006","unstructured":"Smolen JS, Van Der Heijde DMFM, St.Clair EW, , et al. Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial. Arthritis Rheum. 2006;54(3):702\u201310.","journal-title":"Arthritis Rheum"},{"issue":"3","key":"725_CR49","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1136\/annrheumdis-2013-204573","volume":"73","author":"JS Smolen","year":"2014","unstructured":"Smolen JS, Landew\u00e9 R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492\u2013509.","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"725_CR50","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/annrheumdis-2015-207524","volume":"75","author":"JS Smolen","year":"2016","unstructured":"Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75(1):3\u201315.","journal-title":"Ann Rheum Dis"},{"issue":"24","key":"725_CR51","doi-asserted-by":"publisher","first-page":"18138","DOI":"10.1074\/jbc.M000379200","volume":"275","author":"CF Terry","year":"2000","unstructured":"Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem. 2000;275(24):18138\u201344.","journal-title":"J Biol Chem"},{"issue":"4","key":"725_CR52","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1684\/ecn.2016.0382","volume":"27","author":"GC Martelossi Cebinelli","year":"2016","unstructured":"Martelossi Cebinelli GC, Paiva Trugilo K, Badar\u00f3 Garcia S, Braj\u00e3o de Oliveira K. TGF-\u03b21 functional polymorphisms: a review. Eur Cytokine Netw. 2016;27(4):81\u20139.","journal-title":"Eur Cytokine Netw"}],"container-title":["Clinical and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-021-00725-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10238-021-00725-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-021-00725-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T04:11:20Z","timestamp":1667016680000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10238-021-00725-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,27]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["725"],"URL":"https:\/\/doi.org\/10.1007\/s10238-021-00725-9","relation":{},"ISSN":["1591-8890","1591-9528"],"issn-type":[{"value":"1591-8890","type":"print"},{"value":"1591-9528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,27]]},"assertion":[{"value":"16 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"This study was conducted after approval by the Institutional Research Ethics Committees of University of Londrina, Paran\u00e1, Brazil (CAAE: 06405812.1.0000.5231). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}