{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T10:15:50Z","timestamp":1774952150256,"version":"3.50.1"},"reference-count":275,"publisher":"IMR Press","issue":"3","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Primary Sj\u00f6gren\u2019s syndrome (pSS) is a systemic autoimmune disease defined by exocrine gland infiltration and systemic involvement. The management of pSS is hampered by three persistent challenges: seronegativity, heterogeneity, and delayed diagnosis. Up to one-third of patients lack anti-Sj\u00f6gren\u2019s-syndrome-related antigen A\/B (SSA\/SSB) autoantibodies, contributing to misclassification and delayed recognition. Recent studies have expanded the autoantibody repertoire, identifying novel targets such as anti-D-aminoacyl-tRNA deacylase 2 (DTD2), anti-retroelement silencing factor-1 (RESF1), and anti-calreticulin (CALR), as well as multiplex panels including anti-salivary protein-1 (SP-1), anti-parotid secretory protein (PSP), and anti-carbonic anhydrase VI (CA6). These can detect disease before conventional seroconversion, thus offering diagnostic value for seronegative cases. The greatest challenge remains early detection, as the current reliance on biopsy and late-appearing serologies overlooks subclinical disease. In this context, non-invasive fluid biomarkers are transformative, with salivary and tear fluid proteomics (\u03b22-microglobulin, clusterin, matrix metalloproteinase-9), exosomal micro ribonucleic acid (miRNAs), and metabolomic fingerprints providing sensitive indicators of glandular dysfunction and immune activation. When combined with machine learning, integrated multi-omics panels can achieve diagnostic accuracies comparable to biopsy while enabling prognostic stratification. Emerging approaches also leverage artificial intelligence (AI) to refine biomarker discovery and clinical translation. AI-assisted ultrasonography enables reproducible quantification of glandular inflammation, while the application of integrative AI models to multi-omics datasets can identify biomarker signatures with superior predictive accuracy. Such tools have the potential to accelerate early diagnosis, automate risk prediction, and guide precision therapeutics in real time. The future use of biomarker panels in clinical practice should reduce the time to diagnosis, thereby facilitating the anticipation of risk and the provision of therapy based on the underlying cause. In this review, we describe how pSS exemplifies some of the problems inherent in contemporary autoimmunity. This multifaceted and diverse condition is now well-positioned to benefit from integrative, biomarker-driven methodologies, which should lead to improved patient outcomes.<\/jats:p>","DOI":"10.31083\/fbl44757","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:36:33Z","timestamp":1774949793000},"source":"Crossref","is-referenced-by-count":0,"title":["Precision Diagnostics in Primary Sj\u00f6gren\u2019s Syndrome: Advances in Biomarkers, Epigenetic Markers, Immune Pathways, and Clinical Translation"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2371-800X","authenticated-orcid":true,"given":"Thao Thi","family":"Do","sequence":"first","affiliation":[{"name":"Oral Diagnosis and Periodontology Department, Faculty of Odonto-Stomatology, Can Tho University of Medicine and Pharmacy, 900000 Can Tho, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0221-2427","authenticated-orcid":true,"given":"Vy Thuy","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Oral Diagnosis and Periodontology Department, Faculty of Odonto-Stomatology, Can Tho University of Medicine and Pharmacy, 900000 Can Tho, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3821-8360","authenticated-orcid":true,"given":"Kim Tran Thien","family":"Duong","sequence":"additional","affiliation":[{"name":"Oral Diagnosis and Periodontology Department, Faculty of Odonto-Stomatology, Can Tho University of Medicine and Pharmacy, 900000 Can Tho, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5942-4525","authenticated-orcid":true,"given":"Huy Gia","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, 900000 Can Tho, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5374-9442","authenticated-orcid":true,"given":"Duong Nguyen Thuy","family":"Le","sequence":"additional","affiliation":[{"name":"Oral Diagnosis and Periodontology Department, Faculty of Odonto-Stomatology, Can Tho University of Medicine and Pharmacy, 900000 Can Tho, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9955-1272","authenticated-orcid":true,"given":"Quan Minh Mai","family":"Le","sequence":"additional","affiliation":[{"name":"Faculty of Odonto-Stomatology, College of Health Sciences, Nam Can Tho University, 900000 Can Tho, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6867-6244","authenticated-orcid":true,"given":"Thu Ngoc","family":"Trinh","sequence":"additional","affiliation":[{"name":"Oral Diagnosis and Periodontology Department, Faculty of Odonto-Stomatology, Can Tho University of Medicine and Pharmacy, 900000 Can Tho, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1443-7197","authenticated-orcid":true,"given":"Tin Hoang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, 900000 Can Tho, Vietnam"},{"name":"Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, 112304 Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Go\u00ebb V, Salle V, Duhaut P, Jouen F, Smail A, Ducroix JP, et al. Clinical significance of autoantibodies recognizing Sj\u00f6gren\u2019s syndrome A (SSA), SSB, calpastatin and alpha-fodrin in primary Sj\u00f6gren\u2019s syndrome. Clinical and Experimental Immunology. 2007; 148: 281\u2013287.","DOI":"10.1111\/j.1365-2249.2007.03337.x"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Zhang Y, Chen JQ, Yang JY, Liao JH, Wu TH, Yu XB, et al. Sex Difference in Primary Sj\u00f6gren Syndrome: A Medical Records Review Study. Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases. 2023; 29: e78\u2013e85.","DOI":"10.1097\/RHU.0000000000001962"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Qin B, Wang J, Yang Z, Yang M, Ma N, Huang F, et al. Epidemiology of primary Sj\u00f6gren\u2019s syndrome: a systematic review and meta-analysis. Annals of the Rheumatic Diseases. 2015; 74: 1983\u20131989.","DOI":"10.1136\/annrheumdis-2014-205375"},{"key":"ref4","unstructured":"Ng WF (ed.) Sjogren\u2019s Syndrome. Oxford University Press: UK. 2016."},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Fox RI. Sj\u00f6gren\u2019s syndrome. Lancet (London, England). 2005; 366: 321\u2013331.","DOI":"10.1016\/S0140-6736(05)66990-5"},{"key":"ref6","unstructured":"Hern\u00e1ndez-Molina G, \u00c1vila-Casado C, Hern\u00e1ndez-Hern\u00e1ndez C, Recillas-Gispert C, S\u00e1nchez-Guerrero J. Performance of the 2016 ACR\/EULAR SS classification criteria in patients with secondary Sj\u00f6gren\u2019s syndrome. Clinical and Experimental Rheumatology. 2020; 38: 130\u2013133."},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Basiaga ML, Stern SM, Mehta JJ, Edens C, Randell RL, Pomorska A, et al. Childhood Sj\u00f6gren syndrome: features of an international cohort and application of the 2016 ACR\/EULAR classification criteria. Rheumatology (Oxford, England). 2021; 60: 3144\u20133155.","DOI":"10.1093\/rheumatology\/keaa757"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Gianordoli APE, Laguardia RVRB, Santos MCFS, Jorge FC, da Silva Salom\u00e3o A, Caser LC, et al. Prevalence of Sj\u00f6gren\u2019s syndrome according to 2016 ACR-EULAR classification criteria in patients with systemic lupus erythematosus. Advances in Rheumatology (London, England). 2023; 63: 11.","DOI":"10.1186\/s42358-022-00280-1"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Chen J, He Q, Yang J, Wu T, Huang Z, Zhang Y, et al. Anti-SSA\/SSB-negative primary Sj\u00f6gren\u2019s syndrome showing different clinical phenotypes: a retrospective study of 934 cases. Advances in Rheumatology (London, England). 2023; 63: 21.","DOI":"10.1186\/s42358-023-00304-4"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Mihai A, Elena NA, Jurcut C, Florin BC, Anghel D, Opris-Belinski D, et al. AB0599 CLINICAL AND SEROLOGICAL CHARACTERISTICS OF SERONEGATIVE PRIMARY SJ\u00d6GREN\u2019S SYNDROME PATIENTS. Annals of the Rheumatic Diseases. 2023; 82: 1500.","DOI":"10.1136\/annrheumdis-2023-eular.731"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Beckman KA, Luchs J, Milner MS, Ambrus JL, Jr. The Potential Role for Early Biomarker Testing as Part of a Modern, Multidisciplinary Approach to Sj\u00f6gren\u2019s Syndrome Diagnosis. Advances in Therapy. 2017; 34: 799\u2013812.","DOI":"10.1007\/s12325-017-0501-3"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Wang B, Chen S, Zheng Q, Li Y, Zhang X, Xuan J, et al. Early diagnosis and treatment for Sj\u00f6gren\u2019s syndrome: current challenges, redefined disease stages and future prospects. Journal of Autoimmunity. 2021; 117: 102590.","DOI":"10.1016\/j.jaut.2020.102590"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Chen W, Cao H, Lin J, Olsen N, Zheng SG. Biomarkers for Primary Sj\u00f6gren\u2019s Syndrome. Genomics, Proteomics & Bioinformatics. 2015; 13: 219\u2013223.","DOI":"10.1016\/j.gpb.2015.06.002"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Peng J, Feinstein D, DeSimone S, Gentile P. A Review of the Tear Film Biomarkers Used to Diagnose Sjogren\u2019s Syndrome. International Journal of Molecular Sciences. 2024; 25: 10380.","DOI":"10.3390\/ijms251910380"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Engelke F, Budde P, De Vita S, D\u00f6rner T, Ernst D, Gras J, et al. Identification of novel autoantibodies in Sj\u00f6gren\u2019s disease. Frontiers in Immunology. 2025; 16: 1524940.","DOI":"10.3389\/fimmu.2025.1524940"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Parker M, Zheng Z, Lasarev MR, Larsen MC, Vande Loo A, Alexandridis RA, et al. Novel autoantibodies help diagnose anti-SSA antibody negative Sj\u00f6gren disease and predict abnormal labial salivary gland pathology. Annals of the Rheumatic Diseases. 2024; 83: 1169\u20131180.","DOI":"10.1136\/ard-2023-224936"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Zhang K, Luo Z, Yao X, Lu D, Hong T, Zhu X, et al. Identification of Epigenetic Alteration of the IFI44L Gene in B Cells of Sjogren\u2019s Syndrome as a Clinical Biomarker and Molecular Significance. Journal of Inflammation Research. 2025; 18: 2499\u20132512.","DOI":"10.2147\/JIR.S503309"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Zhong Y, Zhang W, Liu D, Zeng Z, Liao S, Cai W, et al. Screening biomarkers for Sjogren\u2019s Syndrome by computer analysis and evaluating the expression correlations with the levels of immune cells. Frontiers in Immunology. 2023; 14: 1023248.","DOI":"10.3389\/fimmu.2023.1023248"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Jonsson R, Brokstad KA, Jonsson MV, Delaleu N, Skarstein K. Current concepts on Sj\u00f6gren\u2019s syndrome - classification criteria and biomarkers. European Journal of Oral Sciences. 2018; 126: 37\u201348.","DOI":"10.1111\/eos.12536"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Psianou K, Panagoulias I, Papanastasiou AD, de Lastic AL, Rodi M, Spantidea PI, et al. Clinical and immunological parameters of Sj\u00f6gren\u2019s syndrome. Autoimmunity Reviews. 2018; 17: 1053\u20131064.","DOI":"10.1016\/j.autrev.2018.05.005"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Goules AV, Kapsogeorgou EK, Tzioufas AG. Insight into pathogenesis of Sj\u00f6gren\u2019s syndrome: Dissection on autoimmune infiltrates and epithelial cells. Clinical Immunology (Orlando, Fla.). 2017; 182: 30\u201340.","DOI":"10.1016\/j.clim.2017.03.007"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Chivasso C, Sarrand J, Perret J, Delporte C, Soyfoo MS. The Involvement of Innate and Adaptive Immunity in the Initiation and Perpetuation of Sj\u00f6gren\u2019s Syndrome. International Journal of Molecular Sciences. 2021; 22: 658.","DOI":"10.3390\/ijms22020658"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Baldini C, Chatzis LG, Fulvio G, La Rocca G, Pontarini E, Bombardieri M. Pathogenesis of Sj\u00f6gren\u2019s disease: one year in review 2024. Clinical and Experimental Rheumatology. 2024; 42: 2336\u20132343.","DOI":"10.55563\/clinexprheumatol\/i8iszc"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Kiripolsky J, McCabe LG, Kramer JM. Innate immunity in Sj\u00f6gren\u2019s syndrome. Clinical Immunology (Orlando, Fla.). 2017; 182: 4\u201313.","DOI":"10.1016\/j.clim.2017.04.003"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Yao Y, Ma JF, Chang C, Xu T, Gao CY, Gershwin ME, et al. Immunobiology of T Cells in Sj\u00f6gren\u2019s Syndrome. Clinical Reviews in Allergy & Immunology. 2021; 60: 111\u2013131.","DOI":"10.1007\/s12016-020-08793-7"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"He J, Jiang J, Baumgart K. Candidate autoantibodies for primary Sj\u00f6gren\u2019s syndrome: where are they now? Clinical and Experimental Rheumatology. 2022; 40: 2387\u20132394.","DOI":"10.55563\/clinexprheumatol\/vmqtz4"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Cui L, Elzakra N, Xu S, Xiao GG, Yang Y, Hu S. Investigation of three potential autoantibodies in Sjogren\u2019s syndrome and associated MALT lymphoma. Oncotarget. 2017; 8: 30039\u201330049.","DOI":"10.18632\/oncotarget.15613"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Nocturne G, Mariette X. B cells in the pathogenesis of primary Sj\u00f6gren syndrome. Nature Reviews. Rheumatology. 2018; 14: 133\u2013145.","DOI":"10.1038\/nrrheum.2018.1"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Ma\u015bli\u0144ska M. The role of Epstein-Barr virus infection in primary Sj\u00f6gren\u2019s syndrome. Current Opinion in Rheumatology. 2019; 31: 475\u2013483.","DOI":"10.1097\/BOR.0000000000000622"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Thorlacius GE, Bj\u00f6rk A, Wahren-Herlenius M. Genetics and epigenetics of primary Sj\u00f6gren syndrome: implications for future therapies. Nature Reviews. Rheumatology. 2023; 19: 288\u2013306.","DOI":"10.1038\/s41584-023-00932-6"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Khatri B, Tessneer KL, Rasmussen A, Aghakhanian F, Reksten TR, Adler A, et al. Genome-wide association study identifies Sj\u00f6gren\u2019s risk loci with functional implications in immune and glandular cells. Nature Communications. 2022; 13: 4287.","DOI":"10.1038\/s41467-022-30773-y"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Shen L, Suresh L, Lindemann M, Xuan J, Kowal P, Malyavantham K, et al. Novel autoantibodies in Sjogren\u2019s syndrome. Clinical Immunology (Orlando, Fla.). 2012; 145: 251\u2013255.","DOI":"10.1016\/j.clim.2012.09.013"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Hubschman S, Rojas M, Kalavar M, Kloosterboer A, Sabater AL, Galor A. Association Between Early Sj\u00f6gren Markers and Symptoms and Signs of Dry Eye. Cornea. 2020; 39: 311\u2013315.","DOI":"10.1097\/ICO.0000000000002171"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Thatayatikom A, Jun I, Bhattacharyya I, Berg K, Lee YJ, Kim Y, et al. The Diagnostic Performance of Early Sj\u00f6gren\u2019s Syndrome Autoantibodies in Juvenile Sj\u00f6gren\u2019s Syndrome: The University of Florida Pediatric Cohort Study. Frontiers in Immunology. 2021; 12: 704193.","DOI":"10.3389\/fimmu.2021.704193"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Karakus S, Baer AN, Agrawal D, Gurakar M, Massof RW, Akpek EK. Utility of Novel Autoantibodies in the Diagnosis of Sj\u00f6gren\u2019s Syndrome Among Patients With Dry Eye. Cornea. 2018; 37: 405\u2013411.","DOI":"10.1097\/ICO.0000000000001471"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Proctor GB, Shaalan AM. Disease-Induced Changes in Salivary Gland Function and the Composition of Saliva. Journal of Dental Research. 2021; 100: 1201\u20131209.","DOI":"10.1177\/00220345211004842"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Bhattarai KR, Junjappa R, Handigund M, Kim HR, Chae HJ. The imprint of salivary secretion in autoimmune disorders and related pathological conditions. Autoimmunity Reviews. 2018; 17: 376\u2013390.","DOI":"10.1016\/j.autrev.2017.11.031"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Teos LY, Zhang Y, Cotrim AP, Swaim W, Won JH, Ambrus J, et al. IP3R deficit underlies loss of salivary fluid secretion in Sj\u00f6gren\u2019s Syndrome. Scientific Reports. 2015; 5: 13953.","DOI":"10.1038\/srep13953"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Kamounah S, Sembler-M\u00f8ller ML, Nielsen CH, Pedersen AML. Sj\u00f6gren\u2019s syndrome: novel insights from proteomics and miRNA expression analysis. Frontiers in Immunology. 2023; 14: 1183195.","DOI":"10.3389\/fimmu.2023.1183195"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Sandhya P, Kabeerdoss J, Christudoss P, Arulraj R, Mandal SK, Janardana R, et al. Salivary free light chains and salivary immunoglobulins as potential non-invasive biomarkers in primary Sj\u00f6gren\u2019s syndrome. International Journal of Rheumatic Diseases. 2022; 25: 61\u201369.","DOI":"10.1111\/1756-185X.14242"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Wang M, Huang J, Lu M, Zhang S, Ding C. ENaC in the Rabbit Lacrimal Gland and its Changes During Sj\u00f6gren Syndrome and Pregnancy. Eye & Contact Lens. 2015; 41: 297\u2013303.","DOI":"10.1097\/ICL.0000000000000123"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Zhang X, Liao Z, Chen Y, Lu H, Wang A, Shi Y, et al. A non-invasive model for diagnosis of primary Sjogren\u2019s disease based on salivary biomarkers, serum autoantibodies, and Schirmer\u2019s test. Arthritis Research & Therapy. 2024; 26: 217.","DOI":"10.1186\/s13075-024-03459-7"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Sembler-M\u00f8ller ML, Belstr\u00f8m D, Locht H, Pedersen AML. Proteomics of saliva, plasma, and salivary gland tissue in Sj\u00f6gren\u2019s syndrome and non-Sj\u00f6gren patients identify novel biomarker candidates. Journal of Proteomics. 2020; 225: 103877.","DOI":"10.1016\/j.jprot.2020.103877"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Di Giorgi N, Cecchettini A, Michelucci E, Signore G, Ceccherini E, Ferro F, et al. Salivary Proteomics Markers for Preclinical Sj\u00f6gren\u2019s Syndrome: A Pilot Study. Biomolecules. 2022; 12: 738.","DOI":"10.3390\/biom12060738"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Finamore F, Cecchettini A, Ceccherini E, Signore G, Ferro F, Rocchiccioli S, et al. Characterization of Extracellular Vesicle Cargo in Sj\u00f6gren\u2019s Syndrome through a SWATH-MS Proteomics Approach. International Journal of Molecular Sciences. 2021; 22: 4864.","DOI":"10.3390\/ijms22094864"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Kuo MT, Fang PC, Chao TL, Chen A, Lai YH, Huang YT, et al. Tear Proteomics Approach to Monitoring Sj\u00f6gren Syndrome or Dry Eye Disease. International Journal of Molecular Sciences. 2019; 20: 1932.","DOI":"10.3390\/ijms20081932"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Li Z, Mu Y, Guo C, You X, Liu X, Li Q, et al. Analysis of the saliva metabolic signature in patients with primary Sj\u00f6gren\u2019s syndrome. PloS One. 2022; 17: e0269275.","DOI":"10.1371\/journal.pone.0269275"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Piacenza Florezi G, Pereira Barone F, Izidoro MA, Soares-Jr JM, Coutinho-Camillo CM, Louren\u00e7o SV. Targeted saliva metabolomics in Sj\u00f6gren\u2019s syndrome. Clinics (Sao Paulo, Brazil). 2024; 79: 100459.","DOI":"10.1016\/j.clinsp.2024.100459"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Yamashiro K, Hamada T, Mori K, Nishi K, Nakamura M, Beppu M, et al. Exosome-Derived microRNAs from Mouthrinse Have the Potential to Be Novel Biomarkers for Sj\u00f6gren Syndrome. Journal of Personalized Medicine. 2022; 12: 1483.","DOI":"10.3390\/jpm12091483"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Alevizos I, Alexander S, Turner RJ, Illei GG. MicroRNA expression profiles as biomarkers of minor salivary gland inflammation and dysfunction in Sj\u00f6gren\u2019s syndrome. Arthritis and Rheumatism. 2011; 63: 535\u2013544.","DOI":"10.1002\/art.30131"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Giovannetti F, Pontecorvi P, Megiorni F, Armentano M, Alisi L, Romano E, et al. Conjunctival MicroRNA Expression Signature in Primary Sj\u00f6gren\u2019s Syndrome Dry Eye: A NanoString-Based Bioinformatic Analysis. Investigative Ophthalmology & Visual Science. 2025; 66: 80.","DOI":"10.1167\/iovs.66.4.80"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Pauley KM, Stewart CM, Gauna AE, Dupre LC, Kuklani R, Chan AL, et al. Altered miR-146a expression in Sj\u00f6gren\u2019s syndrome and its functional role in innate immunity. European Journal of Immunology. 2011; 41: 2029\u20132039.","DOI":"10.1002\/eji.201040757"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Hillen MR, Blokland SL, Chouri E, Lopes AP, Kruize AA, Hack CE, et al. THU0268 Decreased Expression of MIR-130A and MIR-708 in Type-1 Classical Dendritic Cells of Sj\u00f6gren\u2019s Syndrome Patients Indicates Their Dysregulation. Annals of the Rheumatic Diseases. 2016; 75: 284.","DOI":"10.1136\/annrheumdis-2016-eular.4074"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Xuan J, Wang Y, Xiong Y, Qian H, He Y, Shi G. Investigation of autoantibodies to SP-1 in Chinese patients with primary Sj\u00f6gren\u2019s syndrome. Clinical Immunology (Orlando, Fla.). 2018; 188: 58\u201363.","DOI":"10.1016\/j.clim.2017.12.008"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Bunya VY, Ying GS, Maguire MG, Kuklinski E, Lin MC, Peskin E, et al. Prevalence of Novel Candidate Sjogren Syndrome Autoantibodies in the Dry Eye Assessment and Management (DREAM) Study. Cornea. 2018; 37: 1425\u20131430.","DOI":"10.1097\/ICO.0000000000001714"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Mona M, Mondello S, Hyon JY, Saleh W, Han K, Lee HJ, et al. Clinical usefulness of anti-muscarinic type 3 receptor autoantibodies in patients with primary Sj\u00f6gren\u2019s syndrome. Clinical and Experimental Rheumatology. 2020; 39: 795\u2013803.","DOI":"10.55563\/clinexprheumatol\/gy6udz"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Li Y, Zhang J, Liu X, Ganesan K, Shi G. Identification of inflammatory markers as indicators for disease progression in primary Sj\u00f6gren syndrome. European Cytokine Network. 2024; 35: 1\u201312.","DOI":"10.1684\/ecn.2024.0496"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Liu Y, Di G, Hu S, Zhao T, Xu X, Wang X, et al. 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Expression of BAFF and BAFF receptors in primary Sj\u00f6gren\u2019s syndrome patients with ectopic germinal center-like structures. Clinical and Experimental Medicine. 2020; 20: 615\u2013626.","DOI":"10.1007\/s10238-020-00637-0"},{"key":"ref88","doi-asserted-by":"publisher","unstructured":"Eslami M, Schneider P. Function, occurrence and inhibition of different forms of BAFF. Current Opinion in Immunology. 2021; 71: 75\u201380.","DOI":"10.1016\/j.coi.2021.06.009"},{"key":"ref89","doi-asserted-by":"publisher","unstructured":"Kelly AL, Nelson RJ, Sara R, Alberto S. Sj\u00f6gren Syndrome: New Insights in the Pathogenesis and Role of Nuclear Medicine. Journal of Clinical Medicine. 2022; 11: 5227.","DOI":"10.3390\/jcm11175227"},{"key":"ref90","doi-asserted-by":"publisher","unstructured":"Xu Y, Han J, Fan Z, Liang S. Transcriptomics explores potential mechanisms for the development of Primary Sjogren\u2019s syndrome to diffuse large B-cell lymphoma in B cells. 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Elevated expression of Toll-like receptor 7 and its correlation with clinical features in patients with primary Sj\u00f6gren\u2019s syndrome. Advances in Rheumatology (London, England). 2024; 64: 17.","DOI":"10.1186\/s42358-024-00360-4"},{"key":"ref95","doi-asserted-by":"publisher","unstructured":"Punnanitinont A, Kramer JM. Sex-specific differences in primary Sj\u00f6gren\u2019s disease. Frontiers in Dental Medicine. 2023; 4: 1168645.","DOI":"10.3389\/fdmed.2023.1168645"},{"key":"ref96","doi-asserted-by":"publisher","unstructured":"Souyris M, Cenac C, Azar P, Daviaud D, Canivet A, Grunenwald S, et al. TLR7 escapes X chromosome inactivation in immune cells. Science Immunology. 2018; 3: eaap8855.","DOI":"10.1126\/sciimmunol.aap8855"},{"key":"ref97","doi-asserted-by":"publisher","unstructured":"Fairweather D, Beetler DJ, McCabe EJ, Lieberman SM. Mechanisms underlying sex differences in autoimmunity. 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Estrogen regulation of apoptosis: how can one hormone stimulate and inhibit? Breast Cancer Research: BCR. 2009; 11: 206.","DOI":"10.1186\/bcr2255"},{"key":"ref105","doi-asserted-by":"publisher","unstructured":"Benchabane S, Slimani-Kaddouri A, Acheli D, Bendimerad-Iratene T, Mesbah R, Touil-Boukoffa C. Association between Increased Bcl-2, Fas and FasL Levels and Inflammation Extent in Labial Salivary Glands During Primary Sj\u00f6gren\u2019s Syndrome. Endocrine, Metabolic & Immune Disorders Drug Targets. 2022; 22: 328\u2013338.","DOI":"10.2174\/1871530321666210809155147"},{"key":"ref106","doi-asserted-by":"publisher","unstructured":"Cutolo M, Straub RH. Sex steroids and autoimmune rheumatic diseases: state of the art. Nature Reviews. Rheumatology. 2020; 16: 628\u2013644.","DOI":"10.1038\/s41584-020-0503-4"},{"key":"ref107","doi-asserted-by":"publisher","unstructured":"Bouma HR, Bootsma H, van Nimwegen JF, Haacke EA, Spijkervet FK, Vissink A, et al. Aging and Immunopathology in Primary Sj\u00f6gren\u2019s Syndrome. Current Aging Science. 2015; 8: 202\u2013213.","DOI":"10.2174\/1874609808666150727112826"},{"key":"ref108","doi-asserted-by":"publisher","unstructured":"McCoy SS, Woodham M, Bartels CM, Saldanha IJ, Bunya VY, Maerz N, et al. Symptom-Based Cluster Analysis Categorizes Sj\u00f6gren\u2019s Disease Subtypes: An International Cohort Study Highlighting Disease Severity and Treatment Discordance. Arthritis & Rheumatology (Hoboken, N.J.). 2022; 74: 1569\u20131579.","DOI":"10.1002\/art.42238"},{"key":"ref109","doi-asserted-by":"publisher","unstructured":"Lee JJ, Park YJ, Park M, Yim HW, Park SH, Kwok SK. Longitudinal analysis of symptom-based clustering in patients with primary Sjogren\u2019s syndrome: a prospective cohort study with a 5-year follow-up period. Journal of Translational Medicine. 2021; 19: 394.","DOI":"10.1186\/s12967-021-03051-6"},{"key":"ref110","doi-asserted-by":"publisher","unstructured":"Trutschel D, Bost P, Mariette X, Bondet V, Llibre A, Posseme C, et al. Variability of Primary Sj\u00f6gren\u2019s Syndrome Is Driven by Interferon-\u03b1 and Interferon-\u03b1 Blood Levels Are Associated With the Class II HLA-DQ Locus. Arthritis & Rheumatology (Hoboken, N.J.). 2022; 74: 1991\u20132002.","DOI":"10.1002\/art.42265"},{"key":"ref111","doi-asserted-by":"publisher","unstructured":"Hall JC, Baer AN, Shah AA, Criswell LA, Shiboski CH, Rosen A, et al. Molecular Subsetting of Interferon Pathways in Sj\u00f6gren\u2019s Syndrome. Arthritis & Rheumatology (Hoboken, N.J.). 2015; 67: 2437\u20132446.","DOI":"10.1002\/art.39204"},{"key":"ref112","doi-asserted-by":"publisher","unstructured":"Traianos EY, Locke J, Lendrem D, Bowman S, Hargreaves B, Macrae V, et al. Serum CXCL13 levels are associated with lymphoma risk and lymphoma occurrence in primary Sj\u00f6gren\u2019s syndrome. Rheumatology International. 2020; 40: 541\u2013548.","DOI":"10.1007\/s00296-020-04524-5"},{"key":"ref113","doi-asserted-by":"publisher","unstructured":"Loureiro-Amigo J, Franco-Jarava C, Perurena-Prieto J, Palacio C, Mart\u00ednez-Valle F, Sol\u00e1ns-Laqu\u00e9 R. Serum CXCL13, BAFF, IL-21 and IL-22 levels are related to disease activity and lymphocyte profile in primary Sj\u00f6gren\u2019s syndrome. Clinical and Experimental Rheumatology. 2021; 39: 131\u2013139.","DOI":"10.55563\/clinexprheumatol\/fp741f"},{"key":"ref114","doi-asserted-by":"publisher","unstructured":"Nguyen Y, Nocturne G, Henry J, Ng WF, Belkhir R, Desmoulins F, et al. Identification of distinct subgroups of Sj\u00f6gren\u2019s disease by cluster analysis based on clinical and biological manifestations: data from the cross-sectional Paris-Saclay and the prospective ASSESS cohorts. The Lancet. Rheumatology. 2024; 6: e216\u2013e225.","DOI":"10.1016\/S2665-9913(23)00340-5"},{"key":"ref115","doi-asserted-by":"publisher","unstructured":"Lu DQ, Yao XY, Ren YT, Zhang KY, Zhu XC, Hong T, et al. Genome-wide DNA methylation sequencing reveals epigenetic features and potential biomarkers of Sj\u00f6gren syndrome. International Journal of Rheumatic Diseases. 2023; 26: 2223\u20132232.","DOI":"10.1111\/1756-185X.14918"},{"key":"ref116","unstructured":"Ziemanski JF, Szalai AJ. Inflammation mediated by TNF\u03b1 or IFN\u03b3 upregulates gene expression of major complement proteins by conjunctival epithelial cells. Investigative Ophthalmology & Visual Science. 2023; 64: 671."},{"key":"ref117","doi-asserted-by":"publisher","unstructured":"Parisis D, Sarrand J, Cabrol X, Delporte C, Soyfoo MS. Clinical Profile of Patients with Primary Sj\u00f6gren\u2019s Syndrome with Non-Identified Antinuclear Autoantibodies. Diagnostics (Basel, Switzerland). 2024; 14: 935.","DOI":"10.3390\/diagnostics14090935"},{"key":"ref118","doi-asserted-by":"publisher","unstructured":"Gupta L, Edavalath S, Choudhary N, Aggarwal A. Hypergammaglobulinemic Purpura as the First Presentation of Juvenile Onset Sj\u00f6gren Syndrome-Case-Based Review of Literature. Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases. 2021; 27: S357\u2013S361.","DOI":"10.1097\/RHU.0000000000001582"},{"key":"ref119","doi-asserted-by":"publisher","unstructured":"He S, Zhen X, Hu Y. Juvenile primary Sjogren\u2019s syndrome with cutaneous involvement. Clinical Rheumatology. 2021; 40: 3687\u20133694.","DOI":"10.1007\/s10067-021-05656-0"},{"key":"ref120","doi-asserted-by":"publisher","unstructured":"Aiyegbusi O, McGregor L, McGeoch L, Kipgen D, Geddes CC, Stevens KI. Renal Disease in Primary Sj\u00f6gren\u2019s Syndrome. 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Revista Colombiana de Reumatolog\u00eda (English Edition). 2024; 31: 185\u2013192.","DOI":"10.1016\/j.rcreue.2023.02.014"},{"key":"ref161","doi-asserted-by":"publisher","unstructured":"Shao H, Wu Y, Tao X, Liu Q, Ran C, Jin L, et al. The titers of antinuclear antibodies are associated with the degree of inflammation and organ damage in Primary Sj\u00f6gren\u2019s Syndrome. Clinical and Experimental Medicine. 2024; 24: 96.","DOI":"10.1007\/s10238-024-01357-5"},{"key":"ref162","doi-asserted-by":"publisher","unstructured":"Jin Y, Li J, Chen J, Shao M, Zhang R, Liang Y, et al. Tissue-Specific Autoantibodies Improve Diagnosis of Primary Sj\u00f6gren\u2019s Syndrome in the Early Stage and Indicate Localized Salivary Injury. Journal of Immunology Research. 2019; 2019: 3642937.","DOI":"10.1155\/2019\/3642937"},{"key":"ref163","doi-asserted-by":"publisher","unstructured":"De Langhe E, Bossuyt X, Shen L, Malyavantham K, Ambrus JL, Suresh L. 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Rheumatology. 2022; 18: 133\u2013145.","DOI":"10.1038\/s41584-021-00726-8"},{"key":"ref175","doi-asserted-by":"publisher","unstructured":"Xiong Z, Li M, Ma Y, Li R, Bao Y. GMQN: A Reference-Based Method for Correcting Batch Effects and Probe Bias in HumanMethylation BeadChip. Frontiers in Genetics. 2022; 12: 810985.","DOI":"10.3389\/fgene.2021.810985"},{"key":"ref176","doi-asserted-by":"publisher","unstructured":"Collins GS, Moons KG, Dhiman P, Riley RD, Beam AL, Van Calster B, et al. TRIPOD+ AI statement: updated guidance for reporting clinical prediction models that use regression or machine learning methods [published erratum in BMJ. 2024; 385: e078378. doi: 0.1136\/bmj-2023-078378]. BMJ. 2024; 385: q902.","DOI":"10.1136\/bmj.q902"},{"key":"ref177","doi-asserted-by":"publisher","unstructured":"Witte T. Diagnostic markers of Sj\u00f6gren\u2019s syndrome. Developments in Ophthalmology. 2010; 45: 123\u2013128.","DOI":"10.1159\/000315025"},{"key":"ref178","doi-asserted-by":"publisher","unstructured":"Brito-Zer\u00f3n P, Baldini C, Bootsma H, Bowman SJ, Jonsson R, Mariette X, et al. Sj\u00f6gren syndrome. Nature Reviews. Disease Primers. 2016; 2: 16047.","DOI":"10.1038\/nrdp.2016.47"},{"key":"ref179","doi-asserted-by":"publisher","unstructured":"Jung JY, Kim JW, Kim HA, Suh CH. Salivary Biomarkers in Patients with Sj\u00f6gren\u2019s Syndrome-A Systematic Review. International Journal of Molecular Sciences. 2021; 22: 12903.","DOI":"10.3390\/ijms222312903"},{"key":"ref180","doi-asserted-by":"publisher","unstructured":"Sembler-M\u00f8ller ML, Belstr\u00f8m D, Locht H, Pedersen AML. Combined serum anti-SSA\/Ro and salivary TRIM29 reveals promising high diagnostic accuracy in patients with primary Sj\u00f6gren\u2019s syndrome. 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Annals of the New York Academy of Sciences. 1993; 694: 72\u201377.","DOI":"10.1111\/j.1749-6632.1993.tb18343.x"},{"key":"ref184","doi-asserted-by":"publisher","unstructured":"Liu X, Wang H, Wang X, Jiang X, Jin Y, Han Y, et al. Identification and verification of inflammatory biomarkers for primary Sj\u00f6gren\u2019s syndrome. Clinical Rheumatology. 2024; 43: 1335\u20131352.","DOI":"10.1007\/s10067-024-06901-y"},{"key":"ref185","doi-asserted-by":"publisher","unstructured":"Saegusa K, Ishimaru N, Yanagi K, Arakaki R, Ogawa K, Saito I, et al. Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity. The Journal of Clinical Investigation. 2002; 110: 361\u2013369.","DOI":"10.1172\/JCI14682"},{"key":"ref186","doi-asserted-by":"publisher","unstructured":"Klinngam W, Janga SR, Lee C, Ju Y, Yarber F, Shah M, et al. Inhibition of Cathepsin S Reduces Lacrimal Gland Inflammation and Increases Tear Flow in a Mouse Model of Sj\u00f6gren\u2019s Syndrome. Scientific Reports. 2019; 9: 9559.","DOI":"10.1038\/s41598-019-45966-7"},{"key":"ref187","doi-asserted-by":"publisher","unstructured":"Li S, Zheng H, Guan J. Salivary Biomarkers in the Diagnosis of Sjogren\u2019s Syndrome: A Review of Current Research Progress. Journal of Innovations in Medical Research. 2023; 2: 16\u201321.","DOI":"10.56397\/jimr\/2023.07.03"},{"key":"ref188","doi-asserted-by":"publisher","unstructured":"Grus FH, Podust VN, Bruns K, Lackner K, Fu S, Dalmasso EA, et al. SELDI-TOF-MS ProteinChip array profiling of tears from patients with dry eye. 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Springer International Publishing: Cham. 2019.","DOI":"10.1007\/978-3-030-43658-2_15"},{"key":"ref245","doi-asserted-by":"publisher","unstructured":"Geng Y, Zhang X, Zhang Z. Pos0928 deep learning based assessment of salivary gland ultrasonography images for supporting the diagnosis of primary sjogren\u2019s syndrome. Annals of the Rheumatic Diseases. 2023; 82: 775\u2013776.","DOI":"10.1136\/annrheumdis-2023-eular.4614"},{"key":"ref246","doi-asserted-by":"publisher","unstructured":"Niu X, Zhou Y, Xu J, Xue Q, Xu X, Li J, et al. Deep learning in the precise assessment of primary Sj\u00f6gren\u2019s syndrome based on ultrasound images. Rheumatology (Oxford, England). 2025; 64: 2242\u20132251.","DOI":"10.1093\/rheumatology\/keae312"},{"key":"ref247","doi-asserted-by":"publisher","unstructured":"Bourguiba R, Aicha AB, Nouira N, Charfi M, Bouzaidi K, Bellakhal S, et al. 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RMD Open. 2021; 7: e001503.","DOI":"10.1136\/rmdopen-2020-001503"},{"key":"ref250","unstructured":"Leehan KM, Pezant NP, Rasmussen A, Grundahl K, Moore JS, Radfar L, et al. Minor salivary gland fibrosis in Sj\u00f6gren\u2019s syndrome is elevated, associated with focus score and not solely a consequence of aging. Clinical and Experimental Rheumatology. 2018; 36: 80\u201388."},{"key":"ref251","doi-asserted-by":"publisher","unstructured":"L\u00f3pez-Villalobos EF, Mu\u00f1oz-Valle JF, Palafox-S\u00e1nchez CA, Garc\u00eda-Arellano S, Mart\u00ednez-Fern\u00e1ndez DE, Orozco-Barocio G, et al. Cytokine profiles and clinical characteristics in primary Sj\u00f6gren\u00b4s syndrome patient groups. Journal of Clinical Laboratory Analysis. 2021; 35: e23629.","DOI":"10.1002\/jcla.23629"},{"key":"ref252","doi-asserted-by":"publisher","unstructured":"Zhou L, Wang H, Zhang H, Wang F, Wang W, Cao Q, et al. 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Journal of Translational Autoimmunity. 2024; 9: 100248.","DOI":"10.1016\/j.jtauto.2024.100248"},{"key":"ref255","doi-asserted-by":"publisher","unstructured":"Xiang N, Xu H, Zhou Z, Wang J, Cai P, Wang L, et al. Single-cell transcriptome profiling reveals immune and stromal cell heterogeneity in primary Sj\u00f6gren\u2019s syndrome. iScience. 2023; 26: 107943.","DOI":"10.1016\/j.isci.2023.107943"},{"key":"ref256","doi-asserted-by":"publisher","unstructured":"Devauchelle-Pensec V, Zabotti A, Carvajal-Alegria G, Filipovic N, Jousse-Joulin S, De Vita S. Salivary gland ultrasonography in primary Sj\u00f6gren\u2019s syndrome: opportunities and challenges. Rheumatology (Oxford, England). 2021; 60: 3522\u20133527.","DOI":"10.1093\/rheumatology\/kez079"},{"key":"ref257","doi-asserted-by":"publisher","unstructured":"Manfr\u00e8 V, Giovannini I, Zandonella Callegher S, Lorenzon M, Pegolo E, Tel A, et al. Ultrasound and Bioptic Investigation of Patients with Primary Sj\u00f6gren\u2019s Syndrome. Journal of Clinical Medicine. 2021; 10: 1171.","DOI":"10.3390\/jcm10061171"},{"key":"ref258","doi-asserted-by":"publisher","unstructured":"Duquesne J, Basseto L, Claye C, Barnes M, Pontarini E, Gallagher-Syed A, et al. Machine learning to classify the focus score and Sj\u00f6gren\u2019s disease using digitalised salivary gland biopsies: a retrospective cohort study. The Lancet. Rheumatology. 2025; 7: e864\u2013e872.","DOI":"10.1016\/S2665-9913(25)00181-X"},{"key":"ref259","doi-asserted-by":"publisher","unstructured":"Gan M, Peng Y, Ying Y, Zhang K, Chen Y. Machine learning differentiation of rheumatoid arthritis-Sj\u00f6gren\u2019s syndrome overlap from Sj\u00f6gren\u2019s syndrome with polyarthritis. Frontiers in Immunology. 2025; 16: 1614631.","DOI":"10.3389\/fimmu.2025.1614631"},{"key":"ref260","doi-asserted-by":"publisher","unstructured":"Xie H, Deng YM, Li JY, Xie KH, Tao T, Zhang JF. Predicting the risk of primary Sj\u00f6gren\u2019s syndrome with key N7-methylguanosine-related genes: A novel XGBoost model. Heliyon. 2024; 10: e31307.","DOI":"10.1016\/j.heliyon.2024.e31307"},{"key":"ref261","doi-asserted-by":"publisher","unstructured":"Shi Z, Ding Y, Dong X, Li G, Li B, Hou J, et al. The diagnostic value and clinical relevance of salivary gland ultrasound in patients with highly suspected Sj\u00f6gren\u2019s Disease: a prospective monocentric study. Arthritis Research & Therapy. 2025; 27: 175.","DOI":"10.1186\/s13075-025-03642-4"},{"key":"ref262","doi-asserted-by":"publisher","unstructured":"Olivier A, Hoffmann C, Jousse-Joulin S, Mansour A, Bressollette L, Clement B. Machine and Deep Learning Approaches Applied to Classify Gougerot-Sj\u00f6gren Syndrome and Jointly Segment Salivary Glands. Bioengineering (Basel, Switzerland). 2023; 10: 1283.","DOI":"10.3390\/bioengineering10111283"},{"key":"ref263","doi-asserted-by":"publisher","unstructured":"Willemink MJ, Koszek WA, Hardell C, Wu J, Fleischmann D, Harvey H, et al. Preparing Medical Imaging Data for Machine Learning. Radiology. 2020; 295: 4\u201315.","DOI":"10.1148\/radiol.2020192224"},{"key":"ref264","doi-asserted-by":"publisher","unstructured":"Schmidt NS, Fana V, Danielsen MA, Lindegaard HM, Voss A, Horn HC, et al. The impact of an ultrasound atlas for scoring salivary glands in primary Sj\u00f6gren\u2019s syndrome: a pilot study. Clinical Rheumatology. 2023; 42: 3275\u20133281.","DOI":"10.1007\/s10067-023-06696-4"},{"key":"ref265","doi-asserted-by":"publisher","unstructured":"Kise Y, Ikeda H, Fujii T, Fukuda M, Ariji Y, Fujita H, et al. Preliminary study on the application of deep learning system to diagnosis of Sj\u00f6gren\u2019s syndrome on CT images. Dento Maxillo Facial Radiology. 2019; 48: 20190019.","DOI":"10.1259\/dmfr.20190019"},{"key":"ref266","doi-asserted-by":"publisher","unstructured":"Kise Y, Fukuda M, Shibata T, Funakoshi T, Ariji Y, Ariji E. Preliminary approach to creation of a prediction model for diagnosis of Sj\u00f6gren\u2019s syndrome using radiomics and machine learning techniques on computed tomography images of the parotid glands. Imaging Science in Dentistry. 2025; 55: 189\u2013196.","DOI":"10.5624\/isd.20250022"},{"key":"ref267","doi-asserted-by":"publisher","unstructured":"Pecorelli L, Klein K. Insights into Patient Heterogeneity in Sj\u00f6gren\u2019s Disease. International Journal of Molecular Sciences. 2025; 26: 6367.","DOI":"10.3390\/ijms26136367"},{"key":"ref268","doi-asserted-by":"publisher","unstructured":"Dong J, Wang Z, Xu Y, Liang S. Exploration common biomarkers and pathogenesis of primary Sj\u00f6gren\u2019s syndrome and interstitial lung disease by machine learning and weighted gene co-expression networks. PloS One. 2025; 20: e0333070.","DOI":"10.1371\/journal.pone.0333070"},{"key":"ref269","doi-asserted-by":"publisher","unstructured":"Ren Y, Xia W, Wu J, Yang Z, Jiang Y, Wen Y, et al. Artificial intelligence-based prediction of organ involvement in Sjogren\u2019s syndrome using labial gland biopsy whole-slide images. Clinical Rheumatology. 2025; 44: 2919\u20132927.","DOI":"10.1007\/s10067-025-07518-5"},{"key":"ref270","doi-asserted-by":"publisher","unstructured":"He W, Lu Y, Shi R, An Q, Zhao J, Gao X, et al. Application of omics in Sj\u00f6gren\u2019s syndrome. Inflammation Research. 2023; 72: 2089\u20132109.","DOI":"10.1007\/s00011-023-01797-x"},{"key":"ref271","doi-asserted-by":"publisher","unstructured":"Glaab E, Rauschenberger A, Banzi R, Gerardi C, Garcia P, Demotes J. Biomarker discovery studies for patient stratification using machine learning analysis of omics data: a scoping review. BMJ Open. 2021; 11: e053674.","DOI":"10.1136\/bmjopen-2021-053674"},{"key":"ref272","doi-asserted-by":"publisher","unstructured":"Pezoulas VC, Goules A, Kalatzis F, Chatzis L, Kourou KD, Venetsanopoulou A, et al. Addressing the clinical unmet needs in primary Sj\u00f6gren\u2019s Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts. Computational and Structural Biotechnology Journal. 2022; 20: 471\u2013484.","DOI":"10.1016\/j.csbj.2022.01.002"},{"key":"ref273","doi-asserted-by":"publisher","unstructured":"Thiele M, Villesen IF, Niu L, Johansen S, Sulek K, Nishijima S, et al. Opportunities and barriers in omics-based biomarker discovery for steatotic liver diseases. 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