{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T01:24:52Z","timestamp":1794014692647,"version":"4.8.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the NIHR Birmingham Biomedical Research Centre"},{"name":"Vidi-grant from the Dutch Research Council"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by the presence of autoantibodies against modified proteins, known as anti-modified protein autoantibodies (AMPAs). While the relationship between different AMPA isotypes and various risk factors remains poorly understood, investigating this association is important for a deeper understanding of RA pathophysiology. Smoking, has its primary effects in the lungs, and it remains unclear whether smoking is preferentially linked to specific AMPA isotypes, such as IgA, which could suggest a mucosal origin. Therefore, we set out to investigate the association between smoking, genetic risk factors for RA, and the presence of specific AMPA isotypes, particular IgA.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In 618 RA patients, anti-citrullinated protein antibodies (ACPA-) and anti-acetylated protein antibodies (AAPA-) IgA, -IgG and -IgM and RF-IgA and -IgM were measured by ELISA. Associations with genetic risk factors, smoking and autoantibodies were assessed with logistic regression analysis. For replication, a comprehensive meta-analysis incorporating 3309 RA patients was performed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Smoking was primarily associated with IgA AMPA, with associations that prevailed after correcting for the concurrent presence of AMPA IgG (ACPA-IgA OR 1.89 [1.14\u20133.12], AAPA-IgA 2.30 [1.35\u20133.94]). To further substantiate these results, we performed a meta-analysis of 3309 RA patients and observed that smoking was again predominantly associated with the combined presence of ACPA-IgA in addition to ACPA-IgG (OR 2.05 [1.69\u20132.49], <jats:italic>p<\/jats:italic>\u2009&lt; 0.001) versus the single presence of ACPA-IgG (OR 1.18 [0.97\u20131.44], <jats:italic>p<\/jats:italic>\u2009= 0.11). A gene-environment interaction between the most important genetic risk factor for RA (the HLA shared epitope alleles) and smoking was only seen in patients that were both ACPA-IgG and ACPA-IgA positive, but not in patients who were only positive for ACPA-IgG.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>These data provide a pivotal refinement of existing knowledge regarding risk factor associations for RA and lend novel support to the hypothesis that smoking may exert its effect on RA by the induction of local (auto)immune responses at mucosal sites.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13075-025-03543-6","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T06:21:11Z","timestamp":1746685271000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Smoking as a risk factor for rheumatoid arthritis: predominant association with IgA autoantibodies \u2013 comprehensive analysis of anti-modified protein antibodies with smoking and genetic risk factors in rheumatoid arthritis"],"prefix":"10.1186","volume":"27","author":[{"given":"Tineke J.","family":"van Wesemael","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fraser R.","family":"Morton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith W.","family":"Heutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc P.","family":"Maurits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie L.","family":"Dorj\u00e9e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom W. J.","family":"Huizinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Raza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene E. M.","family":"Toes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Knevel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal H. P.","family":"de Jong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sv\u00e4rd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"van der Woude","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"3543_CR1","doi-asserted-by":"crossref","unstructured":"Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010;376(9746):1094\u2013108.","DOI":"10.1016\/S0140-6736(10)60826-4"},{"key":"3543_CR2","doi-asserted-by":"crossref","unstructured":"Derksen V, Huizinga TWJ, van der Woude D. The role of autoantibodies in the pathophysiology of rheumatoid arthritis. Semin Immunopathol. 2017;39(4):437\u201346.","DOI":"10.1007\/s00281-017-0627-z"},{"key":"3543_CR3","doi-asserted-by":"crossref","unstructured":"Huizinga TW, Amos CI, van der Helm-van Mil AH, Chen W, van Gaalen FA, Jawaheer D, et al. Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins.\u00a0Arthritis\u00a0Rheum. 2005;52(11):3433\u20138.","DOI":"10.1002\/art.21385"},{"key":"3543_CR4","doi-asserted-by":"crossref","unstructured":"Kallberg H, Padyukov L, Plenge RM, Ronnelid J, Gregersen PK, van der Helm-van Mil AH, et al. Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am J Hum Genet. 2007;80(5):867\u201375.","DOI":"10.1086\/516736"},{"key":"3543_CR5","doi-asserted-by":"crossref","unstructured":"Reynisdottir G, Karimi R, Joshua V, Olsen H, Hensvold AH, Harju A, et al. Structural changes and antibody enrichment in the lungs are early features of anti-citrullinated protein antibody-positive rheumatoid arthritis. Arthritis Rheumatol. 2014;66(1):31\u20139.","DOI":"10.1002\/art.38201"},{"key":"3543_CR6","doi-asserted-by":"crossref","unstructured":"van Wesemael TJ, Ajeganova S, Humphreys J, Terao C, Muhammad A, Symmons DP, et al. Smoking is associated with the concurrent presence of multiple autoantibodies in rheumatoid arthritis rather than with anti-citrullinated protein antibodies per se: a multicenter cohort study. Arthritis Res Ther. 2016;18(1):285.","DOI":"10.1186\/s13075-016-1177-9"},{"key":"3543_CR7","doi-asserted-by":"crossref","unstructured":"Hedstr\u00f6m AK, R\u00f6nnelid J, Klareskog L, Alfredsson L. Complex Relationships of Smoking, HLA-DRB1 Genes, and Serologic Profiles in Patients With Early Rheumatoid Arthritis: Update From a Swedish Population-Based Case\u00a0Control Study.\u00a0Arthritis Rheumatol\u00a0(Hoboken, NJ). 2019;71(9):1504\u201311.","DOI":"10.1002\/art.40852"},{"key":"3543_CR8","doi-asserted-by":"crossref","unstructured":"Makrygiannakis D, Hermansson M, Ulfgren AK, Nicholas AP, Zendman AJ, Eklund A, et al. Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells. Ann Rheum Dis. 2008;67(10):1488\u201392.","DOI":"10.1136\/ard.2007.075192"},{"key":"3543_CR9","doi-asserted-by":"crossref","unstructured":"Willis VC, Demoruelle MK, Derber LA, Chartier-Logan CJ, Parish MC, Pedraza IF, et al. Sputum autoantibodies in patients with established rheumatoid arthritis and subjects at risk of future clinically apparent disease. Arthritis Rheum. 2013;65(10):2545\u201354.","DOI":"10.1002\/art.38066"},{"key":"3543_CR10","doi-asserted-by":"crossref","unstructured":"Joshua V, Loberg Haarhaus M, Hensvold A, W\u00e4h\u00e4maa H, Gerstner C, Hansson M, et al. Rheumatoid Arthritis- Specific Autoimmunity in the Lung Before and at the Onset of Disease. Arthritis Rheumatol. 2023;75(11):1910\u201322.","DOI":"10.1002\/art.42549"},{"key":"3543_CR11","doi-asserted-by":"crossref","unstructured":"Simon GM, Cheng J, Gordon JI. Quantitative assessment of the impact of the gut microbiota on lysine epsilon-acetylation of host proteins using gnotobiotic mice. Proc Natl Acad Sci U S A. 2012;109(28):11133\u20138.","DOI":"10.1073\/pnas.1208669109"},{"key":"3543_CR12","doi-asserted-by":"crossref","unstructured":"Shi J, Knevel R, Suwannalai P, van der Linden MP, Janssen GM, van Veelen PA, 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\u20137.","DOI":"10.1073\/pnas.1114465108"},{"key":"3543_CR13","doi-asserted-by":"crossref","unstructured":"Kissel T, Reijm S, Slot LM, Cavallari M, Wortel CM, Vergroesen RD, et al. Antibodies and B cells recognising citrullinated proteins display a broad cross-reactivity towards other post-translational modifications. Ann Rheum Dis. 2020;79(4):472\u201380.","DOI":"10.1136\/annrheumdis-2019-216499"},{"key":"3543_CR14","doi-asserted-by":"crossref","unstructured":"Sahlstr\u00f6m P, Hansson M, Steen J, Amara K, Titcombe PJ, Forsstr\u00f6m B, et al. Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Arthritis. Arthritis Rheumatol. 2020;72(10):1643\u201357.","DOI":"10.1002\/art.41385"},{"key":"3543_CR15","doi-asserted-by":"crossref","unstructured":"Reijm S, Kissel T, Stoeken-Rijsbergen G, Slot LM, Wortel CM, van Dooren HJ, et al. Cross-reactivity of IgM anti-modified protein antibodies in rheumatoid arthritis despite limited mutational load. Arthritis Res Ther. 2021;23(1):230.","DOI":"10.1186\/s13075-021-02609-5"},{"key":"3543_CR16","unstructured":"van Aken J, van Bilsen JH, Allaart CF, Huizinga TW, Breedveld FC. The Leiden Early Arthritis Clinic. Clin Exp Rheumatol. 2003;21(5 Suppl 31):S100\u20135."},{"key":"3543_CR17","doi-asserted-by":"crossref","unstructured":"de Jong PH, Hazes JM, Barendregt PJ, Huisman M, van Zeben D, van der Lubbe PA, et al. Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial. Ann Rheum Dis. 2013;72(1):72\u20138.","DOI":"10.1136\/annrheumdis-2011-201162"},{"key":"3543_CR18","doi-asserted-by":"crossref","unstructured":"Claessen SJ, Hazes JM, Huisman MA, van Zeben D, Luime JJ, Weel AE. Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial. BMC Musculoskelet Disord. 2009;10:71.","DOI":"10.1186\/1471-2474-10-71"},{"key":"3543_CR19","doi-asserted-by":"crossref","unstructured":"Dale J, Paterson C, Tierney A, Ralston SH, Reid DM, Basu N, et al. The Scottish Early Rheumatoid Arthritis (SERA) Study: an inception cohort and biobank. BMC Musculoskelet Disord. 2016;17(1):461.","DOI":"10.1186\/s12891-016-1318-y"},{"key":"3543_CR20","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/1471-2350-7-74","volume":"7","author":"BH Smith","year":"2006","unstructured":"Smith BH, Campbell H, Blackwood D, Connell J, Connor M, Deary IJ, et al. Generation Scotland: the Scottish Family Health Study; a new resource for researching genes and heritability. BMC Med Genet. 2006;7:74.","journal-title":"BMC Med Genet"},{"key":"3543_CR21","doi-asserted-by":"crossref","unstructured":"Verpoort KN, Jol-van der Zijde CM, Papendrecht-van der Voort EA, Ioan-Facsinay A, Drijfhout JW, van Tol MJ, et al. Isotype distribution of anti-cyclic citrullinated peptide antibodies in undifferentiated arthritis and rheumatoid arthritis reflects an ongoing immune response.\u00a0Arthritis Rheum. 2006;54(12):3799\u2013808.","DOI":"10.1002\/art.22279"},{"key":"3543_CR22","doi-asserted-by":"crossref","unstructured":"Nijjar JS, Morton FR, Bang H, Buckley CD, van der Heijde D, Gilmour A, et al. The impact of autoantibodies against citrullinated, carbamylated, and acetylated peptides on radiographic progression in patients with new-onset rheumatoid arthritis: an observational cohort study. Lancet Rheumatol. 2021;3(4):e284\u2013e93.","DOI":"10.1016\/S2665-9913(20)30381-7"},{"key":"3543_CR23","doi-asserted-by":"crossref","unstructured":"van der Horst-Bruinsma IE, Visser H, Hazes JM, Breedveld FC, Verduyn W, Schreuder GM, et al. HLA-DQ-associated predisposition to and dominant HLA-DR-associated protection against rheumatoid arthritis. Hum Immunol. 1999;60(2):152\u20138.","DOI":"10.1016\/S0198-8859(98)00101-3"},{"key":"3543_CR24","doi-asserted-by":"crossref","unstructured":"Cook S, Choi W, Lim H, Luo Y, Kim K, Jia X, et al. Accurate imputation of human leukocyte antigens with CookHLA. Nat Commun. 2021;12(1):1264.","DOI":"10.1038\/s41467-021-21541-5"},{"key":"3543_CR25","doi-asserted-by":"crossref","unstructured":"Feitsma AL, Toes RE, Begovich AB, Chokkalingam AP, de Vries RR, Huizinga TW, et al. Risk of progression from undifferentiated arthritis to rheumatoid arthritis: the effect of the PTPN22 1858T-allele in anti-citrullinated peptide antibody positive patients. Rheumatology (Oxford, England). 2007;46(7):1092\u20135.","DOI":"10.1093\/rheumatology\/kem006"},{"key":"3543_CR26","doi-asserted-by":"crossref","unstructured":"Maurits MP, Wouters F, Niemantsverdriet E, Huizinga TWJ, van den Akker EB, Le Cessie S, et al. The Role of Genetics in Clinically Suspect Arthralgia and Rheumatoid Arthritis Development: A Large Cross-Sectional Study. Arthritis Rheumatol. 2023;75(2):178\u201386.","DOI":"10.1002\/art.42323"},{"key":"3543_CR27","unstructured":"Rothman K. In: Press OOU, editor. Epidemiology An Introduction. 2002. p. 173\u20136."},{"key":"3543_CR28","doi-asserted-by":"crossref","unstructured":"Andersson T, Alfredsson L, K\u00e4llberg H, Zdravkovic S, Ahlbom A. Calculating measures of biological interaction. Eur J Epidemiol. 2005;20(7):575\u20139.","DOI":"10.1007\/s10654-005-7835-x"},{"key":"3543_CR29","doi-asserted-by":"crossref","unstructured":"Sv\u00e4rd A, Skogh T, Alfredsson L, Ilar A, Klareskog L, Bengtsson C, et al. Associations with smoking and shared epitope differ between IgA- and IgG-class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis.\u00a0Arthritis Rheumatol\u00a0(Hoboken, NJ). 2015;67(8):2032\u20137.","DOI":"10.1002\/art.39170"},{"key":"3543_CR30","doi-asserted-by":"crossref","unstructured":"Gr\u00f6nwall C, Liljefors L, Bang H, Hensvold AH, Hansson M, Mathsson-Alm L, et al. A Comprehensive Evaluation of the Relationship Between Different IgG and IgA Anti-Modified Protein Autoantibodies in Rheumatoid Arthritis. Front Immunol. 2021;12:627986.","DOI":"10.3389\/fimmu.2021.627986"},{"key":"3543_CR31","doi-asserted-by":"crossref","unstructured":"de Moel EC, Trouw LA, Terao C, Govind N, Tikly M, El-Gabalawy H, et al. Geo-epidemiology of autoantibodies in rheumatoid arthritis: comparison between four ethnically diverse populations. Arthritis Res Ther. 2023;25(1):37.","DOI":"10.1186\/s13075-023-03009-7"},{"key":"3543_CR32","doi-asserted-by":"crossref","unstructured":"Sv\u00e4rd A, Kastbom A, S\u00f6derlin MK, Reckner-Olsson \u00c5, Skogh T. A comparison between IgG- and IgA-class antibodies to cyclic citrullinated peptides and to modified citrullinated vimentin in early rheumatoid arthritis and very early arthritis. J Rheumatol. 2011;38(7):1265\u201372.","DOI":"10.3899\/jrheum.101086"},{"key":"3543_CR33","doi-asserted-by":"crossref","unstructured":"Regueiro C, Rodriguez-Rodriguez L, Lopez-Mejias R, Nu\u00f1o L, Triguero-Martinez A, Perez-Pampin E, et al. A predominant involvement of the triple seropositive patients and others with rheumatoid factor in the association of\u00a0smoking with rheumatoid arthritis. Sci Rep. 2020;10(1):3355.","DOI":"10.1038\/s41598-020-75520-9"},{"key":"3543_CR34","doi-asserted-by":"crossref","unstructured":"Saint-Andr\u00e9 V, Charbit B, Biton A, Rouilly V, Poss\u00e9m\u00e9 C, Bertrand A, et al. Smoking changes adaptive immunity with persistent effects. Nature. 2024;626(8000):827\u201335.","DOI":"10.1038\/s41586-023-06968-8"},{"key":"3543_CR35","doi-asserted-by":"crossref","unstructured":"Tang B, Liu Q, Ilar A, Wiebert P, H\u00e4gg S, Padyukov L, et al. Occupational inhalable agents constitute major risk factors for rheumatoid arthritis, particularly in the context of genetic predisposition and smoking. Ann Rheum Dis. 2023;82(3):316\u201323.","DOI":"10.1136\/ard-2022-223134"},{"key":"3543_CR36","doi-asserted-by":"crossref","unstructured":"Sv\u00e4rd A, Kastbom A, Sommarin Y, Skogh T. Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis. Immunobiology. 2013;218(2):232\u20137.","DOI":"10.1016\/j.imbio.2012.04.011"},{"key":"3543_CR37","doi-asserted-by":"crossref","unstructured":"Li Y, Guo R, Oduro PK, Sun T, Chen H, Yi Y, et al. The Relationship Between Porphyromonas Gingivalis and Rheumatoid Arthritis: A Meta-Analysis. Front Cell Infect Microbiol. 2022;12:956417.","DOI":"10.3389\/fcimb.2022.956417"},{"key":"3543_CR38","doi-asserted-by":"crossref","unstructured":"Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21(8):895\u2013905.","DOI":"10.1038\/nm.3914"},{"key":"3543_CR39","doi-asserted-by":"crossref","unstructured":"Jiang X, Trouw LA, van Wesemael TJ, Shi J, Bengtsson C, K\u00e4llberg H, et al. Anti-CarP antibodies in two large cohorts of patients with rheumatoid arthritis and their relationship to genetic risk factors, cigarette smoking and other autoantibodies.\u00a0Ann Rheum Dis. 2014;73(10):1761\u20138.","DOI":"10.1136\/annrheumdis-2013-205109"},{"key":"3543_CR40","doi-asserted-by":"crossref","unstructured":"Regueiro C, Casares-Marfil D, Lundberg K, Knevel R, Acosta-Herrera M, Rodriguez-Rodriguez L, et al. HLAB*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive\/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis. Arthritis Rheumatol. 2021;73(6):963\u20139.","DOI":"10.1002\/art.41630"},{"key":"3543_CR41","doi-asserted-by":"crossref","unstructured":"Stork EM, van Rijswijck DMH, van Schie KA, Hoek M, Kissel T, Scherer HU, et al. Antigen-specific Fab profiling achieves molecular-resolution analysis of human autoantibody repertoires in rheumatoid arthritis. Nat Commun. 2024;15(1):3114.","DOI":"10.1038\/s41467-024-47337-x"},{"key":"3543_CR42","doi-asserted-by":"crossref","unstructured":"Meyer PW, Hodkinson B, Ally M, Musenge E, Wadee AA, Fickl H, et al. HLA-DRB1 shared epitope genotyping using the revised classification and its association with circulating autoantibodies, acute phase reactants, cytokines and clinical indices of disease activity in a cohort of South African rheumatoid arthritis patients. Arthritis Res Ther. 2011;13(5):R160.","DOI":"10.1186\/ar3479"},{"key":"3543_CR43","doi-asserted-by":"crossref","unstructured":"Liu WX, Jiang Y, Hu QX, You XB. HLA-DRB1 shared epitope allele polymorphisms and rheumatoid arthritis: a systemic review and meta-analysis. Clin Invest Med. 2016;39(6):E182\u2013e203.","DOI":"10.25011\/cim.v39i6.27487"},{"key":"3543_CR44","doi-asserted-by":"crossref","unstructured":"El-Gabalawy HS, Robinson DB, Hart D, Elias B, Markland J, Peschken CA, et al. Immunogenetic risks of anticyclical citrullinated peptide antibodies in a North American Native population with rheumatoid arthritis and their first-degree relatives. J Rheumatol. 2009;36(6):1130\u20135.","DOI":"10.3899\/jrheum.080855"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-025-03543-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13075-025-03543-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-025-03543-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T06:21:26Z","timestamp":1746685286000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-025-03543-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,8]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3543"],"URL":"https:\/\/doi.org\/10.1186\/s13075-025-03543-6","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,8]]},"assertion":[{"value":"12 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2025","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 protocol of each cohort was approved by the relevant local ethics committee and all participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"101"}}