{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T14:06:36Z","timestamp":1775657196312,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>A variety of autoantibodies have been detected in primary biliary cholangitis (PBC), while the presence of autoantibody clusters and their clinical significance have not been fully understood. We aimed at defining autoantibody clusters and to better understand the clinical features and prognosis of PBC patients based on autoantibody clusters under real-world conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively analyzed 788 inpatients with PBC evaluated between October 2008 and July 2019, and included 537 patients. Nineteen autoantibodies which were measured routinely were investigated for cluster analysis. Two-step clustering, Kaplan-Meier survival, and Cox regression analyses were used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five clusters were defined. A cluster of antinuclear antibodies (ANA) and anti-gp210 positive patients were identified with a high rate of cirrhosis at baseline and low survival rate; a cluster of ANA, anti-centromere antibodies (ACA) and\/or anti-CENP-B female dominant patients with older disease onset, low level of platelet count at baseline, high rate of hepatic decompensation, and low survival rate was also characterized; and another cluster of anti-mitochondrial antibodies (AMA) and\/or AMA-M2, anti-Ro52 and a high rate of anti-gp210 positive patients were identified with a high proportion of male patients and low survival rate. A subgroup of patients with anti-SSA and\/or anti-SSB coexists with SjS was also identified; patients with only AMA and\/or AMA-M2-positive with a benign clinical outcome and relatively high complication of non-alcoholic fatty liver disease (NAFLD) were also identified. Only anti-gp210 was considered as a significant predictor for poor outcomes especially in patients with cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Clustering methods allow the identification of distinct autoantibody profiles of PBC that form clinical subsets and can be useful for personalized approaches to diagnosis, clinical management, and the prediction of clinical outcomes. Anti-gp210 was the strongest predictive factor for poor outcomes especially in PBC patients with cirrhosis under real-world conditions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.1098076","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T13:01:36Z","timestamp":1672837296000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Using two-step cluster analysis to classify inpatients with primary biliary cholangitis based on autoantibodies: A real-world retrospective study of 537 patients in China"],"prefix":"10.3389","volume":"13","author":[{"given":"Dan-Tong","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-Ping","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-Yu","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Min","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai-Ping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Yang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu-Hong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Li","family":"Lou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s41395-018-0390-3","article-title":"Diagnosis and Management of Primary Biliary Cholangitis","volume":"114","author":"Younossi","year":"2019","journal-title":"Am J Gastroenterol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.022","article-title":"EASL clinical practice guidelines: The diagnosis and management of patients with primary biliary cholangitis","volume":"67","year":"2017","journal-title":"J Hepatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(65)91372-3","article-title":"Serological tests in diagnosis of primary biliary cirrhosis","volume":"7390","author":"Walker","year":"1965","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1002\/hep.30145","article-title":"Primary biliary cholangitis: 2018 practice guidance from the American association for the study of liver diseases","volume":"69","author":"Lindor","year":"2019","journal-title":"Hepatology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i29.3616","article-title":"Primary biliary cirrhosis: what do autoantibodies tell us","volume":"16","author":"Hu","year":"2010","journal-title":"World J Gastroenterol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21472","article-title":"Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis","volume":"45","author":"Nakamura","year":"2007","journal-title":"Hepatology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14688","article-title":"Antibodies to gp210 and understanding risk in patients with primary biliary cholangitis","volume":"41","author":"Haldar","year":"2021","journal-title":"Liver Int"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1173","article-title":"A real-world observational cohort of patients with primary biliary cholangitis: TARGET-primary biliary cholangitis study design and rationale","volume":"2","author":"Levy","year":"2018","journal-title":"Hepatol Commun"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100248","article-title":"Real-world experience with obeticholic acid in patients with primary biliary cholangitis","volume":"3","author":"D'Amato","year":"2021","journal-title":"JHEP Rep"},{"key":"B10","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3760\/cma.j.issn.1007-3418.2016.01.004","article-title":"Consensus on the diagnosis and management of primary biliary cirrhosis (cholangitis)","volume":"24","year":"2016","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/BF00432479","article-title":"Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis)","volume":"379","author":"Ludwig","year":"1978","journal-title":"Virchows Arch A Pathol Anat Histol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1002\/hep.510280203","article-title":"Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy","volume":"28","author":"Chazouill\u00e8res","year":"1998","journal-title":"Hepatology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v26.i45.7088","article-title":"Chinese Guidelines on the management of liver cirrhosis (abbreviated version)","volume":"26","author":"Xu","year":"2020","journal-title":"World J Gastroenterol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14521","article-title":"Prognosis of 732 ursodeoxycholic acid-treated patients with primary biliary cholangitis: A single center follow-up study from China","volume":"34","author":"Chen","year":"2019","journal-title":"J Gastroenterol Hepatol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13006","article-title":"The prognosis and management of inactive HBV carriers","author":"Invernizzi","year":"2016","journal-title":"Liver Int"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.130984","article-title":"Cluster analysis of autoantibodies in 852 patients with systemic lupus erythematosus from a single center","volume":"41","author":"Artim-Esen","year":"2014","journal-title":"J Rheumatol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28017","article-title":"The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis","volume":"63","author":"Carbone","year":"2016","journal-title":"Hepatology"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13927","article-title":"The risk predictive values of UK-PBC and GLOBE scoring system in Chinese patients with primary biliary cholangitis: The additional effect of anti-gp210","volume":"45","author":"Yang","year":"2017","journal-title":"Aliment Pharmacol Ther"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.12945\/j.aorta.2016.16.014","article-title":"The mystery of the z-score","volume":"4","author":"Curtis","year":"2016","journal-title":"Aorta (Stamford)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4103\/0974-2069.99622","article-title":"The use of z-scores in paediatric cardiology","volume":"5","author":"Chubb","year":"2012","journal-title":"Ann Pediatr Cardiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.080588","article-title":"Autoantibodies in pediatric systemic lupus erythematosus: Ethnic grouping, cluster analysis, and clinical correlations","volume":"36","author":"Jurenc\u00e1k","year":"2009","journal-title":"J Rheumatol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/art.40906","article-title":"Phenotypes determined by cluster analysis and their survival in the prospective European scleroderma trials and research cohort of patients with systemic sclerosis","volume":"71","author":"Sobanski","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"B23","article-title":"Anti-Ro52 and\/or anti-Ro60 immune reactivity: Autoantibody and disease associations","author":"Zampeli","year":"2020","journal-title":"Clin Exp Rheumatol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s10238-008-0150-6","article-title":"The value of antinuclear antibodies in primary biliary cirrhosis","volume":"8","author":"Gao","year":"2008","journal-title":"Clin Exp Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000557","article-title":"Goals of treatment for improved survival in primary biliary cholangitis: Treatment target should be bilirubin within the normal range and normalization of alkaline phosphatase","volume":"115","author":"Murillo Perez","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1080\/08916930400022954","article-title":"Anti-Ro\/SSA and La\/SSB antibodies","volume":"38","author":"Franceschini","year":"2005","journal-title":"Autoimmunity"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2007.03433.x","article-title":"Antibodies to SS-A\/Ro-52kD and centromere in autoimmune liver disease: A clue to diagnosis and prognosis of primary biliary cirrhosis","volume":"26","author":"Granito","year":"2007","journal-title":"Aliment Pharmacol Ther"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.110","article-title":"Advances in understanding the pathogenesis of primary sj\u00f6gren's syndrome","volume":"9","author":"Nocturne","year":"2013","journal-title":"Nat Rev Rheumatol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.rdc.2017.09.008","article-title":"Rheumatic manifestations in autoimmune liver disease","volume":"44","author":"Selmi","year":"2018","journal-title":"Rheum Dis Clin North Am"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840110504","article-title":"Sj\u00f6gren's syndrome in patients with primary biliary cirrhosis","volume":"11","author":"Tsianos","year":"1990","journal-title":"Hepatology"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1991.tb00470.x","article-title":"Features of sj\u00f6gren's syndrome in patients with primary biliary cirrhosis","volume":"230","author":"Uddenfeldt","year":"1991","journal-title":"J Intern Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30094-9","article-title":"Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis: 3-year results of an international open-label extension study","volume":"4","author":"Trauner","year":"2019","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10051061","article-title":"Real-world clinical management of patients with primary biliary cholangitis-a retrospective multicenter study from Germany","volume":"10","author":"Wilde","year":"2021","journal-title":"J Clin Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-021-08904-y","article-title":"Antimitochondrial antibodies: from bench to bedside","volume":"63","author":"Colapietro","year":"2022","journal-title":"Clin Rev Allergy Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e318261e659","article-title":"Primary biliary cirrhosis is more severe in overweight patients","volume":"47","author":"H\u00edndi","year":"2013","journal-title":"J Clin Gastroenterol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-13-140","article-title":"The role of ursodeoxycholic acid in non-alcoholic steatohepatitis: A systematic review","volume":"13","author":"Xiang","year":"2013","journal-title":"BMC Gastroenterol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.000000000000178","article-title":"The impact of primary biliary cholangitis on non-alcoholic fatty liver disease","volume":"33","author":"Iluz-Freundlich","year":"2021","journal-title":"Eur J Gastroenterol Hepatol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1098076\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T13:01:41Z","timestamp":1672837301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1098076\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,4]]},"references-count":37,"alternative-id":["10.3389\/fimmu.2022.1098076"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1098076","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,4]]},"article-number":"1098076"}}