{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T19:15:25Z","timestamp":1770923725266,"version":"3.50.1"},"reference-count":76,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82241223, U20A20360"],"award-info":[{"award-number":["82241223, U20A20360"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["No. YDZJ202201ZYTS014"],"award-info":[{"award-number":["No. YDZJ202201ZYTS014"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Financial Department of Jilin Province","award":["Grant NO. JLSWSRCZX2020-045"],"award-info":[{"award-number":["Grant NO. JLSWSRCZX2020-045"]}]},{"name":"National Key Research and Development Program of China","award":["2024YFE0213800"],"award-info":[{"award-number":["2024YFE0213800"]}]},{"DOI":"10.13039\/501100011789","name":"department of Science and Technology of Jilin Province","doi-asserted-by":"crossref","award":["BRI202501001GH, 202502001GH"],"award-info":[{"award-number":["BRI202501001GH, 202502001GH"]}],"id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune cholestatic liver disease. Current first-line therapy, ursodeoxycholic acid (UDCA), yields suboptimal response rates, leaving many patients at risk of disease progression. Thus, novel therapeutic targets are urgently needed to slow PBC progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed two-sample Mendelian randomization (MR) to identify proteins causally associated with PBC risk, using protein quantitative trait loci (pQTL) as genetic instruments. The discovery stage utilized PBC genome-wide association study (GWAS) summary statistics from Cordell et al., followed by replication in independent GWAS datasets from the IEU Open GWAS project and the FinnGen consortium. pQTL data were drawn from large-scale plasma (N\u2009=\u20092,656) and cerebrospinal fluid (CSF; N\u2009=\u2009184) proteomic studies. We also conducted sensitivity analyses, including Bayesian colocalization, reverse-causality testing, and phenotype scanning. Identified protein targets were further examined via protein\u2013protein interaction (PPI) network analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three proteins showed significant associations with PBC risk after Bonferroni correction (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20096.35\u2009\u00d7\u200910\n                      <jats:sup>\u22125<\/jats:sup>\n                      ). Elevated plasma\n                      <jats:italic>MANBA<\/jats:italic>\n                      (odds ratio [OR] = 1.29, 95% confidence interval [CI] 1.20\u20131.40, p\u2009=\u20091.22\u2009\u00d7\u200910\n                      <jats:sup>\u221210<\/jats:sup>\n                      ) and CSF\n                      <jats:italic>TNFSF15<\/jats:italic>\n                      (OR = 6.37, 95% CI 2.94\u201313.83, p\u2009=\u20092.79\u2009\u00d7\u200910\n                      <jats:sup>\u22126<\/jats:sup>\n                      ) were associated with higher PBC risk, whereas elevated plasma\n                      <jats:italic>FCRL3<\/jats:italic>\n                      (OR = 0.79, 95% CI 0.73\u20130.86, p\u2009=\u20092.12\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ) was associated with lower risk. Bayesian colocalization analysis indicated that these protein loci and PBC share the same underlying causal variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Elevated plasma\n                      <jats:italic>MANBA<\/jats:italic>\n                      and CSF\n                      <jats:italic>TNFSF15<\/jats:italic>\n                      levels were linked to increased PBC risk, while higher plasma\n                      <jats:italic>FCRL3<\/jats:italic>\n                      was protective. Our findings nominate\n                      <jats:italic>MANBA<\/jats:italic>\n                      and\n                      <jats:italic>TNFSF15<\/jats:italic>\n                      as potential therapeutic targets, while\n                      <jats:italic>FCRL3<\/jats:italic>\n                      may serve as a protective biomarker for PBC management.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0340166","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T18:23:29Z","timestamp":1770920609000},"page":"e0340166","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploration and discovery of treatment targets for primary biliary cholangitis based on plasma and cerebrospinal fluid proteomics: A multicenter mendelian randomization study"],"prefix":"10.1371","volume":"21","author":[{"given":"Jianxin","family":"Xi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengnan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason Chi Shing","family":"Law","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianglong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8652-6403","authenticated-orcid":true,"given":"Guan Huei","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongqi","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4656-4955","authenticated-orcid":true,"given":"Guoyue","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuguo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"issue":"1","key":"pone.0340166.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3350\/cmh.2020.0028","article-title":"Current understanding of primary biliary cholangitis","volume":"27","author":"A Tanaka","year":"2021","journal-title":"Clin Mol Hepatol"},{"issue":"10003","key":"pone.0340166.ref002","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1016\/S0140-6736(15)00154-3","article-title":"Primary biliary cirrhosis","volume":"386","author":"EJ Carey","year":"2015","journal-title":"Lancet"},{"issue":"8","key":"pone.0340166.ref003","article-title":"Epidemiology and natural history of primary biliary cholangitis in the chinese: a territory-based study in Hong Kong between 2000 and 2015","volume":"8","author":"K-S Cheung","year":"2017","journal-title":"Clin Transl Gastroenterol"},{"issue":"1","key":"pone.0340166.ref004","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/apt.13448","article-title":"Population-based epidemiology of primary biliary cirrhosis in South Korea","volume":"43","author":"K-A Kim","year":"2016","journal-title":"Aliment Pharmacol Ther"},{"issue":"10","key":"pone.0340166.ref005","doi-asserted-by":"crossref","first-page":"7905","DOI":"10.1007\/s00210-024-03135-2","article-title":"Clinical features, treatment, and outcome of pembrolizumab induced cholangitis","volume":"397","author":"W Fang","year":"2024","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"5","key":"pone.0340166.ref006","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.jhep.2011.10.025","article-title":"Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review","volume":"56","author":"K Boonstra","year":"2012","journal-title":"J Hepatol"},{"key":"pone.0340166.ref007","doi-asserted-by":"crossref","first-page":"102578","DOI":"10.1016\/j.jaut.2020.102578","article-title":"Primary biliary cholangitis with normal alkaline phosphatase: A neglected clinical entity challenging current guidelines","volume":"116","author":"B Terziroli Beretta-Piccoli","year":"2021","journal-title":"J Autoimmun"},{"issue":"1","key":"pone.0340166.ref008","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1515\/cclm-2017-0249","article-title":"The diagnostic accuracy of biomarkers for diagnosis of primary biliary cholangitis (PBC) in anti-mitochondrial antibody (AMA)-negative PBC patients: a review of literature","volume":"56","author":"F de Liso","year":"2017","journal-title":"Clin Chem Lab Med"},{"issue":"4","key":"pone.0340166.ref009","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10637-024-01452-0","article-title":"Clinical characteristics, treatment and outcome of pembrolizumab-induced acute pancreatitis","volume":"42","author":"P Luo","year":"2024","journal-title":"Invest New Drugs"},{"key":"pone.0340166.ref010","doi-asserted-by":"crossref","first-page":"3019378","DOI":"10.1155\/2020\/3019378","article-title":"CD19+CD24hiCD38hi B cell dysfunction in primary biliary cholangitis","volume":"2020","author":"Q Chen","year":"2020","journal-title":"Mediators Inflamm"},{"issue":"6","key":"pone.0340166.ref011","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1002\/hep4.1907","article-title":"Immunoglobulin M: a neglected serum biomarker in treatment-naive primary biliary cholangitis with normal alkaline phosphatase","volume":"6","author":"D Ding","year":"2022","journal-title":"Hepatol Commun"},{"issue":"4","key":"pone.0340166.ref012","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/jgh.14900","article-title":"IgM response is a prognostic biomarker of primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate","volume":"35","author":"K Takano","year":"2020","journal-title":"J Gastroenterol Hepatol"},{"issue":"10","key":"pone.0340166.ref013","article-title":"Serum microRNAs as potential biomarkers of primary biliary cirrhosis","volume":"9","author":"Y Tan","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"pone.0340166.ref014","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s13075-023-03163-y","article-title":"Integrative bioinformatics analysis and experimental validation of key biomarkers for risk stratification in primary biliary cholangitis","volume":"25","author":"S Tian","year":"2023","journal-title":"Arthritis Res Ther"},{"issue":"2","key":"pone.0340166.ref015","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.jhep.2019.04.001","article-title":"Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis","volume":"71","author":"MH Harms","year":"2019","journal-title":"J Hepatol"},{"issue":"3","key":"pone.0340166.ref016","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1136\/gutjnl-2016-313332","article-title":"Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy","volume":"67","author":"R Tang","year":"2018","journal-title":"Gut"},{"issue":"3","key":"pone.0340166.ref017","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/hep.28932","article-title":"Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis","volume":"65","author":"S Samur","year":"2017","journal-title":"Hepatology"},{"issue":"6","key":"pone.0340166.ref018","doi-asserted-by":"crossref","first-page":"445","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":"M Trauner","year":"2019","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"1","key":"pone.0340166.ref019","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41576-020-0268-2","article-title":"Genetics meets proteomics: perspectives for large population-based 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Sun","year":"2018","journal-title":"Nature"},{"issue":"1","key":"pone.0340166.ref023","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1038\/s41467-018-05512-x","article-title":"Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease","volume":"9","author":"C Yao","year":"2018","journal-title":"Nat Commun"},{"issue":"2","key":"pone.0340166.ref024","doi-asserted-by":"crossref","DOI":"10.1136\/egastro-2023-100029","article-title":"New horizons of human genetics in digestive diseases","volume":"1","author":"L Chen","year":"2023","journal-title":"eGastroenterology"},{"issue":"2","key":"pone.0340166.ref025","doi-asserted-by":"crossref","DOI":"10.1136\/egastro-2023-100043","article-title":"First release of Mendelian randomisation book in Chinese","volume":"1","author":"L Chen","year":"2023","journal-title":"eGastroenterology"},{"issue":"1","key":"pone.0340166.ref026","doi-asserted-by":"crossref","DOI":"10.1136\/egastro-2025-100187","article-title":"Attention to the misuse of Mendelian randomisation in medical research","volume":"3","author":"L Chen","year":"2025","journal-title":"eGastroenterology"},{"issue":"1","key":"pone.0340166.ref027","doi-asserted-by":"crossref","DOI":"10.1136\/egastro-2023-100042","article-title":"Incorporating biological and clinical insights into variant choice for Mendelian randomisation: examples and principles","volume":"2","author":"S Burgess","year":"2024","journal-title":"eGastroenterology"},{"issue":"8","key":"pone.0340166.ref028","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1093\/brain\/awad070","article-title":"Potential drug targets for multiple sclerosis identified through Mendelian randomization analysis","volume":"146","author":"J Lin","year":"2023","journal-title":"Brain"},{"issue":"12","key":"pone.0340166.ref029","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/s41588-021-00973-1","article-title":"Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology","volume":"53","author":"W van Rheenen","year":"2021","journal-title":"Nat Genet"},{"key":"pone.0340166.ref030","article-title":"Prospects of Mendelian Randomization in Hepatology: A Comprehensive Literature Review with Practice Guidance Mendelian Randomization and Hepatology","author":"L Chen","year":"2025","journal-title":"Clin Mol Hepatol"},{"issue":"3","key":"pone.0340166.ref031","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.jhep.2021.04.055","article-title":"An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs","volume":"75","author":"HJ Cordell","year":"2021","journal-title":"J Hepatol"},{"issue":"10","key":"pone.0340166.ref032","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/s41588-020-0682-6","article-title":"Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases","volume":"52","author":"J Zheng","year":"2020","journal-title":"Nat Genet"},{"issue":"9","key":"pone.0340166.ref033","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/s41593-021-00886-6","article-title":"Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders","volume":"24","author":"C Yang","year":"2021","journal-title":"Nat Neurosci"},{"key":"pone.0340166.ref034","doi-asserted-by":"crossref","first-page":"8019","DOI":"10.1038\/ncomms9019","article-title":"International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways","volume":"6","author":"HJ Cordell","year":"2015","journal-title":"Nat Commun"},{"issue":"12","key":"pone.0340166.ref035","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1038\/s41588-021-00978-w","article-title":"Large-scale integration of the plasma proteome with genetics and disease","volume":"53","author":"E Ferkingstad","year":"2021","journal-title":"Nat Genet"},{"issue":"11","key":"pone.0340166.ref036","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1007081","article-title":"Orienting the causal relationship between imprecisely measured traits using GWAS summary data","volume":"13","author":"G Hemani","year":"2017","journal-title":"PLoS Genet"},{"issue":"5","key":"pone.0340166.ref037","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1004383","article-title":"Bayesian test for colocalisation between pairs of genetic association studies using summary statistics","volume":"10","author":"C Giambartolomei","year":"2014","journal-title":"PLoS Genet"},{"issue":"22","key":"pone.0340166.ref038","doi-asserted-by":"crossref","first-page":"4851","DOI":"10.1093\/bioinformatics\/btz469","article-title":"PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations","volume":"35","author":"MA Kamat","year":"2019","journal-title":"Bioinformatics"},{"issue":"3","key":"pone.0340166.ref039","doi-asserted-by":"crossref","DOI":"10.1101\/mcs.a003954","article-title":"\u03b2-Mannosidosis caused by a novel homozygous intragenic inverted duplication in MANBA","volume":"5","author":"M Blomqvist","year":"2019","journal-title":"Cold Spring Harb Mol Case Stud"},{"issue":"576","key":"pone.0340166.ref040","article-title":"Kidney disease genetic risk variants alter lysosomal beta-mannosidase (MANBA) expression and disease severity","volume":"13","author":"X Gu","year":"2021","journal-title":"Sci Transl Med"},{"issue":"5","key":"pone.0340166.ref041","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s10637-024-01472-w","article-title":"Clinical characteristics, treatment, and outcomes of nivolumab induced immune thrombocytopenia","volume":"42","author":"L Peng","year":"2024","journal-title":"Invest New Drugs"},{"key":"pone.0340166.ref042","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev-pathol-020712-164014","article-title":"The immunobiology and pathophysiology of primary biliary cirrhosis","volume":"8","author":"GM Hirschfield","year":"2013","journal-title":"Annu Rev Pathol"},{"issue":"2","key":"pone.0340166.ref043","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jhep.2010.03.008","article-title":"Modulation of the microenvironment by senescent biliary epithelial cells may be involved in the pathogenesis of primary biliary cirrhosis","volume":"53","author":"M Sasaki","year":"2010","journal-title":"J Hepatol"},{"issue":"2","key":"pone.0340166.ref044","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s10620-013-2920-6","article-title":"Chemokine-chemokine receptor CCL2-CCR2 and CX3CL1-CX3CR1 axis may play a role in the aggravated inflammation in primary biliary cirrhosis","volume":"59","author":"M Sasaki","year":"2014","journal-title":"Dig Dis Sci"},{"issue":"6","key":"pone.0340166.ref045","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/labinvest.2010.56","article-title":"Autophagy mediates the process of cellular senescence characterizing bile duct damages in primary biliary cirrhosis","volume":"90","author":"M Sasaki","year":"2010","journal-title":"Lab Invest"},{"issue":"17","key":"pone.0340166.ref046","doi-asserted-by":"crossref","first-page":"9772","DOI":"10.1073\/pnas.171308498","article-title":"Identification of a family of Fc receptor homologs with preferential B cell expression","volume":"98","author":"RS Davis","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"pone.0340166.ref047","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1002\/art.34457","article-title":"A functional variant in FCRL3 is associated with higher Fc receptor-like 3 expression on T cell subsets and rheumatoid arthritis disease activity","volume":"64","author":"UD Bajpai","year":"2012","journal-title":"Arthritis Rheum"},{"issue":"12","key":"pone.0340166.ref048","doi-asserted-by":"crossref","first-page":"7518","DOI":"10.4049\/jimmunol.0802230","article-title":"Fc receptor-like 3 protein expressed on IL-2 nonresponsive subset of human regulatory T cells","volume":"182","author":"S Nagata","year":"2009","journal-title":"J Immunol"},{"issue":"9","key":"pone.0340166.ref049","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/intimm\/dxl069","article-title":"Expression pattern of the human FcRH\/IRTA receptors in normal tissue and in B-chronic lymphocytic leukemia","volume":"18","author":"AG Polson","year":"2006","journal-title":"Int Immunol"},{"key":"pone.0340166.ref050","doi-asserted-by":"crossref","first-page":"1161311","DOI":"10.3389\/fimmu.2023.1161311","article-title":"Identification of multiple novel susceptibility genes associated with autoimmune thyroid disease","volume":"14","author":"X Liu","year":"2023","journal-title":"Front Immunol"},{"issue":"11","key":"pone.0340166.ref051","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.3899\/jrheum.110489","article-title":"FCRL3 -169C\/C genotype is associated with anti-citrullinated protein antibody-positive rheumatoid arthritis and with radiographic progression","volume":"38","author":"MT Maehlen","year":"2011","journal-title":"J Rheumatol"},{"issue":"2","key":"pone.0340166.ref052","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3109\/14397595.2013.854066","article-title":"The FCRL3 -169T>C polymorphism might be associated with some autoantibody presence in patients with SLE in a Polish population","volume":"24","author":"P Piotrowski","year":"2014","journal-title":"Mod Rheumatol"},{"key":"pone.0340166.ref053","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.immunol.25.022106.141623","article-title":"Regulatory T cells: mechanisms of differentiation and function","volume":"30","author":"SZ Josefowicz","year":"2012","journal-title":"Annu Rev Immunol"},{"issue":"5","key":"pone.0340166.ref054","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"S Sakaguchi","year":"2008","journal-title":"Cell"},{"issue":"5","key":"pone.0340166.ref055","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2019.12.099","article-title":"Human Fc Receptor-like 3 Inhibits Regulatory T Cell Function and Binds Secretory IgA","volume":"30","author":"S Agarwal","year":"2020","journal-title":"Cell Rep"},{"issue":"3","key":"pone.0340166.ref056","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/toxres\/tfad024","article-title":"Celastrol inhibits gastric cancer cell proliferation, migration, and invasion via the FOXA1\/CLDN4 axis","volume":"12","author":"W Peng","year":"2023","journal-title":"Toxicol Res (Camb)"},{"issue":"1","key":"pone.0340166.ref057","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.cyto.2013.07.005","article-title":"Increased IL-23 and IL-17 expression by peripheral blood cells of patients with primary biliary cirrhosis","volume":"64","author":"C Qian","year":"2013","journal-title":"Cytokine"},{"key":"pone.0340166.ref058","doi-asserted-by":"crossref","first-page":"718841","DOI":"10.3389\/fimmu.2021.718841","article-title":"Interleukin 23 Produced by Hepatic Monocyte-Derived Macrophages Is Essential for the Development of Murine Primary Biliary Cholangitis","volume":"12","author":"D Reuveni","year":"2021","journal-title":"Front 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Lan","year":"2006","journal-title":"Hepatology"},{"issue":"11","key":"pone.0340166.ref062","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1002\/eji.201243068","article-title":"FCRL3 promotes TLR9-induced B-cell activation and suppresses plasma cell differentiation","volume":"43","author":"FJ Li","year":"2013","journal-title":"Eur J Immunol"},{"issue":"9","key":"pone.0340166.ref063","doi-asserted-by":"crossref","first-page":"5502","DOI":"10.4049\/jimmunol.0901982","article-title":"FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B-cell receptor-mediated signaling","volume":"183","author":"Y Kochi","year":"2009","journal-title":"J Immunol"},{"issue":"8","key":"pone.0340166.ref064","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.4049\/jimmunol.161.8.4042","article-title":"Inhibitory and stimulatory functions of paired Ig-like receptor (PIR) family in RBL-2H3 cells","volume":"161","author":"Y Yamashita","year":"1998","journal-title":"J Immunol"},{"key":"pone.0340166.ref065","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jaut.2016.10.003","article-title":"Phenotyping and auto-antibody production by liver-infiltrating B cells in primary sclerosing cholangitis and primary biliary cholangitis","volume":"77","author":"BK Chung","year":"2017","journal-title":"J Autoimmun"},{"issue":"2","key":"pone.0340166.ref066","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/hep.32172","article-title":"E. coli and the etiology of human PBC: Antimitochondrial antibodies and spreading determinants","volume":"75","author":"Y Yang","year":"2022","journal-title":"Hepatology"},{"key":"pone.0340166.ref067","doi-asserted-by":"crossref","first-page":"1184252","DOI":"10.3389\/fimmu.2023.1184252","article-title":"Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis?","volume":"14","author":"Y Yang","year":"2023","journal-title":"Front Immunol"},{"issue":"12","key":"pone.0340166.ref068","first-page":"2107","article-title":"Asymptomatic primary biliary cirrhosis in HTLV-I-associated myelopathy","volume":"88","author":"T Ijichi","year":"1993","journal-title":"Am J Gastroenterol"},{"issue":"4","key":"pone.0340166.ref069","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1080\/00207454.2020.1815735","article-title":"Transverse myelitis associated with primary biliary cirrhosis: clinical, laboratory, and neuroradiological features","volume":"132","author":"M Zhao","year":"2022","journal-title":"Int J Neurosci"},{"issue":"3","key":"pone.0340166.ref070","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S1074-7613(02)00283-2","article-title":"TL1A is a TNF-like ligand for DR3 and TR6\/DcR3 and functions as a T cell costimulator","volume":"16","author":"TS Migone","year":"2002","journal-title":"Immunity"},{"issue":"4","key":"pone.0340166.ref071","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.ajhg.2012.08.010","article-title":"Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population","volume":"91","author":"M Nakamura","year":"2012","journal-title":"Am J Hum Genet"},{"key":"pone.0340166.ref072","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1007\/s12016-015-8472-0","article-title":"Multiple genetic variants associated with primary biliary cirrhosis in a Han Chinese population","volume":"48","author":"M Dong","year":"2015","journal-title":"Clin Rev Allergy Immunol"},{"issue":"7","key":"pone.0340166.ref073","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00439-015-1556-3","article-title":"Human primary biliary cirrhosis-susceptible allele of rs4979462 enhances TNFSF15 expression by binding 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