{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:29:08Z","timestamp":1760059748293,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8K0341"],"award-info":[{"award-number":["CMRPG8K0341"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Although autoimmune diseases differ in their pathogenesis, B cells play a central role in many of them, and alterations in peripheral B cell subpopulations have been observed. Therefore, we aimed to explore the possibility of peripheral B cell subpopulations as a biomarker for autoimmune diseases based on their alternation. Methods: We prospectively collected blood samples from 54 patients with various autoimmune diseases and 65 healthy controls. The percentages of B cell subpopulations were evaluated using flow cytometry. A scoring system was developed and the largest Youden\u2019s index was used to determine the optimal cutoff point. Results: The frequencies of double-negative B cells and antibody-secreting cells were significantly higher in patients than in controls (median: 2.9% vs. 1.5%, p &lt; 0.001; median: 3.6% vs. 2.1%, p = 0.001, respectively). Among the patients, those with systemic lupus erythematosus showed the most impact on the alteration of peripheral B cell subpopulations, which was correlated with disease activity. Furthermore, the scoring system effectively distinguished patients from healthy controls. The area under the receiver operating characteristic curves was 0.752 (95% confidence interval: 0.664\u20130.840), and the optimal cutoff value of \u226510 points yielded a sensitivity and specificity of 70.4% and 70.8%, respectively. Conclusions: Peripheral B cell subpopulations in patients with autoimmune diseases are significantly different from those in healthy individuals and can vary between diseases. Therefore, alterations in B cell populations may be a potential biomarker for diagnosing and evaluating autoimmune diseases.<\/jats:p>","DOI":"10.3390\/diagnostics15131710","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T11:20:11Z","timestamp":1751628011000},"page":"1710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alternation in Peripheral B Cell Subpopulations Is a Potential Biomarker for Autoimmune Diseases\u2014A Cross-Sectional Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0253-5983","authenticated-orcid":false,"given":"Shao-Wei","family":"Ku","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Hua","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huey-Ling","family":"You","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 83102, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7274-3458","authenticated-orcid":false,"given":"Yu-Jih","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Internal Medicine, Division of Geriatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33382, Taiwan"},{"name":"Institute of Biopharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan"},{"name":"Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6442-3713","authenticated-orcid":false,"given":"Wan-Ting","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 83102, Taiwan"},{"name":"School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33382, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sharip, A., and Kunz, J. (2020). Understanding the Pathogenesis of Spondyloarthritis. Biomolecules, 10.","DOI":"10.3390\/biom10101461"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1016\/j.immuni.2022.11.009","article-title":"The pathogenesis of rheumatoid arthritis","volume":"55","author":"Alivernini","year":"2022","journal-title":"Immunity"},{"key":"ref_3","first-page":"e30330","article-title":"An Overview of Systemic Lupus Erythematosus (SLE) Pathogenesis, Classification, and Management","volume":"14","author":"Ameer","year":"2022","journal-title":"Cureus"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s41581-023-00720-1","article-title":"Pathogenesis of autoimmune disease","volume":"19","author":"Pisetsky","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9518137","DOI":"10.1155\/2020\/9518137","article-title":"Peripheral B Cell Subsets in Autoimmune Diseases: Clinical Implications and Effects of B Cell-Targeted Therapies","volume":"2020","author":"Jin","year":"2020","journal-title":"J. Immunol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sanz, I., Wei, C., Jenks, S.A., Cashman, K.S., Tipton, C., Woodruff, M.C., Hom, J., and Lee, F.E. (2019). Challenges and Opportunities for Consistent Classification of Human B Cell and Plasma Cell Populations. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02458"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.jid.2021.05.038","article-title":"B- and Plasma Cell Subsets in Autoimmune Diseases: Translational Perspectives","volume":"142","author":"Dang","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","first-page":"887","article-title":"Combination of B cell biomarkers as independent predictors of response in patients with rheumatoid arthritis treated with rituximab","volume":"33","author":"Tony","year":"2015","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Adlowitz, D.G., Barnard, J., Biear, J.N., Cistrone, C., Owen, T., Wang, W., Palanichamy, A., Ezealah, E., Campbell, D., and Wei, C. (2015). Expansion of Activated Peripheral Blood Memory B Cells in Rheumatoid Arthritis, Impact of B Cell Depletion Therapy, and Biomarkers of Response. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128269"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1002\/art.30466","article-title":"B cell biomarkers of rituximab responses in systemic lupus erythematosus","volume":"63","author":"Vital","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1007\/s13311-021-01006-9","article-title":"Memory B Cells Predict Relapse in Rituximab-Treated Myasthenia Gravis","volume":"18","author":"Bresch","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1186\/s13018-021-02883-8","article-title":"Association among B lymphocyte subset and rheumatoid arthritis in a Chinese population","volume":"16","author":"You","year":"2021","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.gastha.2022.02.012","article-title":"Circulating IgG4(+) Plasmablast Count as a Diagnostic Tool in Autoimmune Pancreatitis","volume":"1","author":"Ciccocioppo","year":"2022","journal-title":"Gastro Hep Adv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/art.1780270401","article-title":"Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria","volume":"27","author":"Valkenburg","year":"1984","journal-title":"Arthritis Rheum."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1136\/ard.2009.108233","article-title":"The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): Validation and final selection","volume":"68","author":"Rudwaleit","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1191\/096120399680411317","article-title":"The American College of Rheumatology criteria for the classification of systemic lupus erythematosus: Strengths, weaknesses, and opportunities for improvement","volume":"8","author":"Smith","year":"1999","journal-title":"Lupus"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1136\/annrheumdis-2013-204424","article-title":"2013 classification criteria for systemic sclerosis: An American college of rheumatology\/European league against rheumatism collaborative initiative","volume":"72","author":"Khanna","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/art.39859","article-title":"2016 American College of Rheumatology\/European League Against Rheumatism Classification Criteria for Primary Sjogren\u2019s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts","volume":"69","author":"Shiboski","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1136\/annrheumdis-2017-211400","article-title":"2016 American College of Rheumatology\/European League Against Rheumatism criteria for minimal, moderate, and major clinical response in adult dermatomyositis and polymyositis: An International Myositis Assessment and Clinical Studies Group\/Paediatric Rheumatology International Trials Organisation Collaborative Initiative","volume":"76","author":"Aggarwal","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_21","first-page":"288","article-title":"Systemic lupus erythematosus disease activity index 2000","volume":"29","author":"Gladman","year":"2002","journal-title":"J. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.2215\/CJN.12791019","article-title":"Kidney Disease, Race, and GFR Estimation","volume":"15","author":"Levey","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/cytob.21162","article-title":"Eight-color immunophenotyping of T-, B-, and NK-cell subpopulations for characterization of chronic immunodeficiencies","volume":"86","author":"Boldt","year":"2014","journal-title":"Cytom. B Clin. Cytom."},{"key":"ref_24","unstructured":"(2021). Validation of Assays Performed by Flow Cytometry (Standard No. CLSI H62)."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/cei.13615","article-title":"Double-negative (DN) B cells: An under-recognized effector memory B cell subset in autoimmunity","volume":"205","author":"Li","year":"2021","journal-title":"Clin. Exp. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.immuni.2018.08.015","article-title":"Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus","volume":"49","author":"Jenks","year":"2018","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/nri3795","article-title":"The generation of antibody-secreting plasma cells","volume":"15","author":"Nutt","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1002\/eji.201848065","article-title":"Autoreactive B-lymphocytes in SLE and RA patients: Isolation and characterisation using extractable nuclear and citrullinated antigens bound to immunobeads","volume":"49","author":"Anez","year":"2019","journal-title":"Eur. J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kosalka-Wegiel, J., Jakiela, B., Dziedzic, R., Milewski, M., Siwiec-Kozlik, A., Zareba, L., Bazan-Socha, S., Sanak, M., Musial, J., and Korkosz, M. (2024). Circulating B Lymphocyte Subsets in Patients with Systemic Lupus Erythematosus. Medicina, 60.","DOI":"10.3390\/medicina60121994"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.4049\/jimmunol.1001946","article-title":"Anergic responses characterize a large fraction of human autoreactive naive B cells expressing low levels of surface IgM","volume":"186","author":"Quach","year":"2011","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/ni.3175","article-title":"Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus","volume":"16","author":"Tipton","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_32","first-page":"32","article-title":"Changes of memory B- and T-cell subsets in lupus nephritis patients","volume":"54","author":"Kosalka","year":"2016","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"R108","DOI":"10.1186\/ar3042","article-title":"Decreased frequency and activated phenotype of blood CD27 IgD IgM B lymphocytes is a permanent abnormality in systemic lupus erythematosus patients","volume":"12","author":"Rodriguez","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.clim.2017.07.010","article-title":"B cell phenotypes, signaling and their roles in secretion of antibodies in systemic lupus erythematosus","volume":"186","author":"Tanaka","year":"2018","journal-title":"Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Yang, M., Zhang, Y., Huang, Y., Wu, J., Xie, Y., Wei, Q., Liao, Z., and Gu, J. (2021). Dynamics of Adaptive Immune Cell and NK Cell Subsets in Patients With Ankylosing Spondylitis After IL-17A Inhibition by Secukinumab. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.738316"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/cei.13616","article-title":"Non-organ-specific autoimmunity in adult 47,XXY Klinefelter patients and higher-grade X-chromosome aneuploidies","volume":"205","author":"Panimolle","year":"2021","journal-title":"Clin. Exp. Immunol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/13\/1710\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:04:34Z","timestamp":1760033074000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/13\/1710"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,4]]},"references-count":36,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["diagnostics15131710"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15131710","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2025,7,4]]}}}