{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:03:53Z","timestamp":1788984233154,"version":"build-2803163510"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,19]],"date-time":"2021-09-19T00:00:00Z","timestamp":1632009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,19]],"date-time":"2021-09-19T00:00:00Z","timestamp":1632009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100020621","name":"Seoul St. Mary\u2019s Hospital","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100020621","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Sjogren\u2019s syndrome (SS) is a heterogenous disease with various phenotypes. We aimed to provide a relevant subclassification based on symptom-based clustering for patients with primary (p) SS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Data from patients in a prospective pSS cohort in Korea were analysed. Latent class analysis (LCA) was performed using patient reported outcomes, including pain, fatigue, dryness, and anxiety\/depression. Clinical and laboratory differences between the classes were analysed. Latent transition analysis (LTA) was applied to the longitudinal data (annually for up to 5\u00a0years) to assess temporal stability of the classifications.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>LCA identified three classes among 341 patients with pSS (i.e., \u2018high symptom burden\u2019, \u2018dryness dominant\u2019, \u2018low symptom burden\u2019). Each group had distinct laboratory and clinical phenotypes. LTA revealed that class membership remained stable over time. Baseline class predicted future salivary gland function and damage accrual represented by a Sjogren\u2019s syndrome disease damage index.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Symptom-based clustering of heterogenous patients with primary Sjogren\u2019s syndrome provided a relevant classification supported by temporal stability over time and distinct phenotypes between the classes. This clustering strategy may provide more homogenous groups of pSS patients for novel treatment development and predict future phenotypic evolvement.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-021-03051-6","type":"journal-article","created":{"date-parts":[[2021,9,19]],"date-time":"2021-09-19T15:02:17Z","timestamp":1632063737000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Longitudinal analysis of symptom-based clustering in patients with primary Sjogren\u2019s syndrome: a prospective cohort study with a 5-year follow-up period"],"prefix":"10.1186","volume":"19","author":[{"given":"Jennifer Jooha","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Jae","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Woo","family":"Yim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Hwan","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Ki","family":"Kwok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,19]]},"reference":[{"issue":"9482","key":"3051_CR1","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/S0140-6736(05)66990-5","volume":"366","author":"RI Fox","year":"2005","unstructured":"Fox RI. Sj\u00f6gren\u2019s syndrome. Lancet. 2005;366(9482):321\u201331.","journal-title":"Lancet"},{"issue":"5","key":"3051_CR2","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1093\/rheumatology\/ket427","volume":"53","author":"C Baldini","year":"2014","unstructured":"Baldini C, Pepe P, Quartuccio L, Priori R, Bartoloni E, Alunno A, et al. Primary Sj\u00f6gren\u2019s syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology. 2014;53(5):839\u201344.","journal-title":"Rheumatology"},{"issue":"1","key":"3051_CR3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/annrheumdis-2019-216114","volume":"79","author":"M Ramos-Casals","year":"2020","unstructured":"Ramos-Casals M, Brito-Zer\u00f3n P, Bombardieri S, Bootsma H, De Vita S, D\u00f6rner T, et al. EULAR recommendations for the management of Sj\u00f6gren\u2019s syndrome with topical and systemic therapies. Ann Rheum Dis. 2020;79(1):3\u201318.","journal-title":"Ann Rheum Dis"},{"issue":"Suppl 118(3)","key":"3051_CR4","first-page":"167","volume":"37","author":"S Fasano","year":"2019","unstructured":"Fasano S, Isenberg DA. Present and novel biologic drugs in primary Sj\u00f6gren\u2019s syndrome. Clin Exp Rheumatol. 2019;37(Suppl 118(3)):167\u201374.","journal-title":"Clin Exp Rheumatol"},{"issue":"3","key":"3051_CR5","doi-asserted-by":"publisher","first-page":"e153","DOI":"10.1016\/S2665-9913(19)30160-2","volume":"2","author":"JF van Nimwegen","year":"2020","unstructured":"van Nimwegen JF, Mossel E, van Zuiden GS, Wijnsma RF, Delli K, Stel AJ, et al. Abatacept treatment for patients with early active primary Sj\u00f6gren\u2019s syndrome: a single-centre, randomised, double-blind, placebo-controlled, phase 3 trial (ASAP-III study). Lancet Rheumatol. 2020;2(3):e153\u201363.","journal-title":"Lancet Rheumatol"},{"issue":"2","key":"3051_CR6","doi-asserted-by":"publisher","first-page":"e85","DOI":"10.1016\/S2665-9913(19)30042-6","volume":"1","author":"JR Tarn","year":"2019","unstructured":"Tarn JR, Howard-Tripp N, Lendrem DW, Mariette X, Saraux A, Devauchelle-Pensec V, et al. Symptom-based stratification of patients with primary Sj\u00f6gren\u2019s syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials. Lancet Rheumatol. 2019;1(2):e85\u201394.","journal-title":"Lancet Rheumatol"},{"issue":"3","key":"3051_CR7","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1001\/jama.2014.7682","volume":"312","author":"JE Gottenberg","year":"2014","unstructured":"Gottenberg JE, Ravaud P, Pu\u00e9chal X, Le Guern V, Sibilia J, Goeb V, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sj\u00f6gren syndrome: the JOQUER randomized clinical trial. JAMA. 2014;312(3):249\u201358.","journal-title":"JAMA"},{"issue":"7","key":"3051_CR8","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1002\/art.40093","volume":"69","author":"SJ Bowman","year":"2017","unstructured":"Bowman SJ, Everett CC, O\u2019Dwyer JL, Emery P, Pitzalis C, Ng WF, et al. Randomized controlled trial of rituximab and cost-effectiveness analysis in treating fatigue and oral dryness in primary Sj\u00f6gren\u2019s syndrome. Arthritis Rheumatol. 2017;69(7):1440\u201350.","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"3051_CR9","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1093\/rheumatology\/keq240","volume":"50","author":"WF Ng","year":"2011","unstructured":"Ng WF, Bowman SJ, Griffiths B. United Kingdom Primary Sjogren\u2019s Syndrome Registry\u2013a united effort to tackle an orphan rheumatic disease. Rheumatology. 2011;50(1):32\u20139.","journal-title":"Rheumatology"},{"key":"3051_CR10","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1037\/tps0000176","volume":"4","author":"K Nylund-Gibson","year":"2018","unstructured":"Nylund-Gibson K, Choi A. Ten frequently asked questions about latent class analysis. Transl Issues Psychol Sci. 2018;4:440\u201361.","journal-title":"Transl Issues Psychol Sci"},{"key":"3051_CR11","doi-asserted-by":"publisher","first-page":"675","DOI":"10.3389\/fpsyg.2018.00675","volume":"9","author":"JH Ryoo","year":"2018","unstructured":"Ryoo JH, Wang C, Swearer SM, Hull M, Shi D. Longitudinal model building using latent transition analysis: an example using school bullying data. Front Psychol. 2018;9:675.","journal-title":"Front Psychol"},{"issue":"1","key":"3051_CR12","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s13075-020-02249-1","volume":"22","author":"K Yoshimoto","year":"2020","unstructured":"Yoshimoto K, Suzuki K, Takei E, Ikeda Y, Takeuchi T. Elevated expression of BAFF receptor, BR3, on monocytes correlates with B cell activation and clinical features of patients with primary Sj\u00f6gren\u2019s syndrome. Arthritis Res Ther. 2020;22(1):157.","journal-title":"Arthritis Res Ther"},{"key":"3051_CR13","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-020-05154-9","author":"V Yazisiz","year":"2020","unstructured":"Yazisiz V, Aslan B, Erbasan F, U\u00e7ar \u0130, \u00d6\u011f\u00fct TS, Terzio\u011flu ME. Clinical and serological characteristics of seronegative primary Sj\u00f6gren\u2019s syndrome: a comparative study. Clin Rheumatol. 2020. https:\/\/doi.org\/10.1007\/s10067-020-05154-9.","journal-title":"Clin Rheumatol"},{"issue":"1","key":"3051_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40169-018-0218-1","volume":"8","author":"PD Burbelo","year":"2019","unstructured":"Burbelo PD, Browne S, Holland SM, Iadarola MJ, Alevizos I. Clinical features of Sj\u00f6gren\u2019s syndrome patients with autoantibodies against interferons. Clin Transl Med. 2019;8(1):1.","journal-title":"Clin Transl Med"},{"issue":"5","key":"3051_CR15","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1093\/rheumatology\/kex490","volume":"57","author":"ILA Bodewes","year":"2018","unstructured":"Bodewes ILA, Al-Ali S, van Helden-Meeuwsen CG, Maria NI, Tarn J, Lendrem DW, et al. Systemic interferon type I and type II signatures in primary Sj\u00f6gren\u2019s syndrome reveal differences in biological disease activity. Rheumatology. 2018;57(5):921\u201330.","journal-title":"Rheumatology"},{"issue":"4","key":"3051_CR16","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1093\/rheumatology\/kez335","volume":"59","author":"JA James","year":"2020","unstructured":"James JA, Guthridge JM, Chen H, Lu R, Bourn RL, Bean K, et al. Unique Sj\u00f6gren\u2019s syndrome patient subsets defined by molecular features. Rheumatology. 2020;59(4):860\u20138.","journal-title":"Rheumatology"},{"key":"3051_CR17","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.jaut.2019.03.008","volume":"100","author":"J Lee","year":"2019","unstructured":"Lee J, Lee J, Baek S, Koh JH, Kim JW, Kim SY, et al. Soluble siglec-5 is a novel salivary biomarker for primary Sjogren\u2019s syndrome. J Autoimmun. 2019;100:114\u20139.","journal-title":"J Autoimmun"},{"issue":"12","key":"3051_CR18","doi-asserted-by":"publisher","first-page":"e83540","DOI":"10.1371\/journal.pone.0083540","volume":"8","author":"SY Park","year":"2013","unstructured":"Park SY, Baek S, Kim S, Yoon SY, Kwon HS, Chang YS, et al. Clinical significance of asthma clusters by longitudinal analysis in Korean asthma cohort. PLoS ONE. 2013;8(12):e83540.","journal-title":"PLoS ONE"},{"issue":"4","key":"3051_CR19","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.jclinepi.2012.09.016","volume":"66","author":"SY Kim","year":"2013","unstructured":"Kim SY, Park JE, Lee YJ, Seo HJ, Sheen SS, Hahn S, et al. Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity. J Clin Epidemiol. 2013;66(4):408\u201314.","journal-title":"J Clin Epidemiol"},{"issue":"5","key":"3051_CR20","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1164\/rccm.201301-0156OC","volume":"188","author":"A Boudier","year":"2013","unstructured":"Boudier A, Curjuric I, Basaga\u00f1a X, Hazgui H, Anto JM, Bousquet J, et al. Ten-year follow-up of cluster-based asthma phenotypes in adults. A pooled analysis of three cohorts. Am J Respir Critical Care Med. 2013;188(5):550\u201360.","journal-title":"Am J Respir Critical Care Med"},{"issue":"20","key":"3051_CR21","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1001\/jama.2019.5791","volume":"321","author":"CW Seymour","year":"2019","unstructured":"Seymour CW, Kennedy JN, Wang S, Chang CH, Elliott CF, Xu Z, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA. 2019;321(20):2003\u201317.","journal-title":"JAMA"},{"issue":"2","key":"3051_CR22","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1001\/jamacardio.2019.4867","volume":"5","author":"RB Patel","year":"2020","unstructured":"Patel RB, Colangelo LA, Reis JP, Lima JAC, Shah SJ, Lloyd-Jones DM. Association of longitudinal trajectory of albuminuria in young adulthood with myocardial structure and function in later life: Coronary Artery Risk Development in Young Adults (CARDIA) Study. JAMA Cardiology. 2020;5(2):184\u201392.","journal-title":"JAMA Cardiology"},{"issue":"7","key":"3051_CR23","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1093\/rheumatology\/kew049","volume":"55","author":"JM Pego-Reigosa","year":"2016","unstructured":"Pego-Reigosa JM, Lois-Iglesias A, R\u00faa-Figueroa \u00cd, Galindo M, Calvo-Al\u00e9n J, de U\u00f1a-\u00c1lvarez J, et al. Relationship between damage clustering and mortality in systemic lupus erythematosus in early and late stages of the disease: cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry. Rheumatology. 2016;55(7):1243\u201350.","journal-title":"Rheumatology"},{"issue":"9","key":"3051_CR24","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1002\/art.40906","volume":"71","author":"V Sobanski","year":"2019","unstructured":"Sobanski V, Giovannelli J, Allanore Y, Riemekasten G, Air\u00f2 P, Vettori S, et al. phenotypes determined by cluster analysis and their survival in the prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis. Arthritis Rheumatol. 2019;71(9):1553\u201370.","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"3051_CR25","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13075-019-2090-9","volume":"22","author":"J Li","year":"2020","unstructured":"Li J, Peng Y, Zhang Y, Zhang P, Liu Z, Lu H, et al. Identifying clinical subgroups in IgG4-related disease patients using cluster analysis and IgG4-RD composite score. Arthritis Res Ther. 2020;22(1):7.","journal-title":"Arthritis Res Ther"},{"issue":"4","key":"3051_CR26","doi-asserted-by":"publisher","first-page":"75","DOI":"10.21037\/atm.2017.02.05","volume":"5","author":"Z Zhang","year":"2017","unstructured":"Zhang Z, Murtagh F, Van Poucke S, Lin S, Lan P. Hierarchical cluster analysis in clinical research with heterogeneous study population: highlighting its visualization with R. Ann Transl Med. 2017;5(4):75.","journal-title":"Ann Transl Med"},{"issue":"7","key":"3051_CR27","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1001\/jama.2020.2278","volume":"324","author":"M Mori","year":"2020","unstructured":"Mori M, Krumholz HM, Allore HG. Using latent class analysis to identify hidden clinical phenotypes. JAMA. 2020;324(7):700\u20131.","journal-title":"JAMA"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-021-03051-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-021-03051-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-021-03051-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,19]],"date-time":"2021-09-19T15:03:11Z","timestamp":1632063791000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-021-03051-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,19]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["3051"],"URL":"https:\/\/doi.org\/10.1186\/s12967-021-03051-6","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,19]]},"assertion":[{"value":"5 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 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":"Informed consent was obtained from all patients according to Declaration of Helsinki principles. This study was approved by the Institutional Review Board of Seoul St. Mary\u2019s Hospital (KC13ONMI0646).","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 that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"394"}}