{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T20:01:43Z","timestamp":1787256103607,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170173"],"award-info":[{"award-number":["82170173"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171777"],"award-info":[{"award-number":["82171777"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371789"],"award-info":[{"award-number":["82371789"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Myasthenia gravis (MG) is an autoimmune disease predominantly driven by autoantibodies targeting acetylcholine receptor (AChR), resulting in muscle weakness. Efgartigimod, a neonatal Fc receptor (FcRn) blocker, reduces pathogenic immunoglobulin G in anti\u2010AChR antibody\u2010positive generalised MG (gMG). This study aimed to identify immune mechanisms underlying MG pathology and response to efgartigimod.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We constructed a single\u2010cell atlas of peripheral immune cells from treatment\u2010na\u00efve and efgartigimod\u2010treated patients with gMG. Comprehensive immunophenotyping was performed to compare the clonal diversity of B\u2010 and T\u2010cell populations, alongside experimental validation to assess the activation of Th17\u2010related pathways before and after FcRn blockade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>B cells in patients with gMG exhibit heightened activation and differentiation, while T cells display distinct pro\u2010inflammatory phenotypes. Enhanced intercellular signalling contributed to the pathogenicity associated with gMG. Efgartigimod mitigated upregulated antigen processing and presentation pathways in MG. Additionally, B\u2010cell clonal diversity and IGHG1\u2010bearing B\u2010cell receptors increased. Transcriptional factor alterations were noted in suboptimal responders. Regulation of T\u2010cell activity, particularly within Th17\u2010related pathways, was associated with remission rates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings underscore immune heterogeneity and dynamics during efgartigimod treatment, providing mechanistic insights into therapeutic response in gMG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      \u2009\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Aberrant B cells and pro\u2010inflammatory T cells contribute critically to generalised myasthenia gravis (gMG) pathogenesis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Neonatal Fc receptor (FcRn) blockade induces immunoglobulin G (IgG) depletion feedback, reflected by increased class\u2010switched BCRs.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Th17 cell proliferation is attenuated following FcRn blockade.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Antigen processing and presentation pathways are downregulated after FcRn blockade in gMG.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70436","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T04:31:38Z","timestamp":1754541098000},"source":"Crossref","is-referenced-by-count":11,"title":["Single\u2010cell atlas reveals heterogeneous response to FcRn blockade in anti\u2010AChR antibody\u2010positive generalised myasthenia gravis"],"prefix":"10.1002","volume":"15","author":[{"given":"Hui\u2010Ning","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology Tianjin Neurological Institute Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Inflammatory Biology Department of Pharmacology School of Basic Medicine Tianjin Medical University  Tianjin China"},{"name":"State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem  Tianjin China"},{"name":"Province and Ministry Co\u2010Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Bioinformatics School of Basic Medicine Tianjin Medical University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Neurological Institute Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Neurological Institute Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Neurological Institute Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Sheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Neurological Institute Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Hainan General Hospital Hainan Affiliated Hospital of Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixiong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology Hainan General Hospital Hainan Affiliated Hospital of Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu\u2010Dong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Neurological Institute Tianjin Medical University General Hospital  Tianjin China"},{"name":"Department of Neurology National Clinical Research Center for Neurological Diseases of China Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2416-9951","authenticated-orcid":false,"given":"Zhigang","family":"Cai","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Inflammatory Biology Department of Pharmacology School of Basic Medicine Tianjin Medical University  Tianjin China"},{"name":"State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem  Tianjin China"},{"name":"Province and Ministry Co\u2010Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Bioinformatics School of Basic Medicine Tianjin Medical University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0659-4597","authenticated-orcid":false,"given":"Chao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Neurological Institute Tianjin Medical University General Hospital  Tianjin China"},{"name":"State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(21)00297\u20100"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra1602678"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500725"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010023\u201004421\u2010y"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.12.001"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.02.006"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.135.5.3360"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801717105"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019037108"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci97911"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(21)00159\u20109"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2012.06817.x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.03.013"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010024\u201001900\u20102"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25021274"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.06.015"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014\u20105793(94)80612\u20108"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014\u20105793(95)00287\u2010j"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201008976\u20106"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830251039"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abq3277"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2017.05.008"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2018.09.007"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.11.001"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202350736"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.034"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02686"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.05.007"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.11.003"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010022\u201001454\u20100"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2007206117"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12825"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70436","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ctm2.70436","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70436","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T04:43:11Z","timestamp":1773981791000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.70436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":32,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/ctm2.70436"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.70436","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"article-number":"e70436"}}