{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:42:50Z","timestamp":1791297770046,"version":"4.1.0"},"reference-count":111,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"104","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2025,2,28]]},"abstract":"<jats:p>Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and Epstein-Barr virus (EBV) infection is a prerequisite for developing the disease. However, the pathogenic mechanisms that lead to MS remain to be determined. Here, we characterized the immune landscape of deep cervical lymph nodes (dcLNs) in newly diagnosed untreated patients with MS (pwMS) using fine-needle aspirations. By combining single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing, we observed increased memory B cells and reduced germinal center B cells with decreased clonality in pwMS. Double-negative memory B cells were increased in pwMS that transcriptionally resembled B cells with a lytic EBV infection. Moreover, EBV-targeting memory CD8 T cells were detected in a subset of pwMS. We also detected increased EBV DNA in dcLNs and elevated viral loads in patient saliva. These findings suggest that EBV-driven B cell dysregulation is a critical mechanism in MS pathogenesis.<\/jats:p>","DOI":"10.1126\/sciimmunol.adl3604","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:58:31Z","timestamp":1740146311000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":23,"title":["Altered immune landscape of cervical lymph nodes reveals Epstein-Barr virus signature in multiple sclerosis"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5963-0379","authenticated-orcid":true,"given":"Joona","family":"Sarkkinen","sequence":"first","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5470-5442","authenticated-orcid":true,"given":"Dawit A.","family":"Yohannes","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2520-2955","authenticated-orcid":true,"given":"Nea","family":"Kreivi","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5996-2913","authenticated-orcid":true,"given":"Pia","family":"D\u00fcrnsteiner","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Elsakova","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2750-4033","authenticated-orcid":true,"given":"Jani","family":"Huuhtanen","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, Helsinki, Finland."},{"name":"Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland."},{"name":"ICAN Digital Precision Cancer Medicine Flagship, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland."},{"name":"Department of Computer Science, Aalto University School of Science, Espoo, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8713-4823","authenticated-orcid":true,"given":"Kirsten","family":"Nowlan","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goran","family":"Kurdo","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3670-0917","authenticated-orcid":true,"given":"Riikka","family":"Linden","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Saarela","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brain Center, Helsinki University Hospital, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-2900","authenticated-orcid":true,"given":"Pentti J.","family":"Tienari","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, Helsinki, Finland."},{"name":"Department of Neurology, Brain Center, Helsinki University Hospital, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-108X","authenticated-orcid":true,"given":"Eliisa","family":"Kek\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9031-4251","authenticated-orcid":true,"given":"Maria","family":"Perdomo","sequence":"additional","affiliation":[{"name":"Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0104-2849","authenticated-orcid":true,"given":"Sini M.","family":"Laakso","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, Helsinki, Finland."},{"name":"Department of Neurology, Brain Center, Helsinki University Hospital, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520970841"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2010.04143.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-014-8496-1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-322941"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000318"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8222"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00770-5"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04432-7"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003220"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458515588581"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2011.01.020"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-051217-111018"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27887-0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0421-4"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11547-017-0829-4"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008879"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000873"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr182"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02469"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458518779951"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2020.112746"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz474"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1146826"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.01.041"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.11.1553"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.07.002"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.023"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.10.006"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.06.012"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2013.05.015"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202254677"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.12.015"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701217"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0667-5"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-120419-022408"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12737"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","unstructured":"R. Browaeys J. Gilis C. Sang-Aram P. De Bleser L. Hoste S. Tavernier D. Lambrechts R. Seurinck Y. Saeys MultiNicheNet: A flexible framework for differential cell-cell communication analysis from multi-sample multi-condition single-cell transcriptomics data. bioRxiv 544751 (2023). https:\/\/doi.org\/10.1101\/2023.06.13.544751.","DOI":"10.1101\/2023.06.13.544751"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02839"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202201615"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2425"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300438"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0071-9"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.ade8162"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43427-4"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.09.001"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301979"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.04.012"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2021.06.006"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.11.006"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.08.015"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02458"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2022.01.003"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0181-4"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv359"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008814"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.015"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23324-4"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1001\/2013.jamaneurol.409"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00834-9"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abb8786"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141132"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04606"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.02.021"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.10.011"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0221-9"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13516"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.01.020"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad199"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baw162"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1112"},{"key":"e_1_3_2_74_2","doi-asserted-by":"crossref","unstructured":"J. Chen D. Yin H. Y. H. Wong X. Duan K. H. O. Yu J. W. K. Ho Vulture: Cloud-enabled scalable mining of microbial reads in public scRNA-seq data. bioRxiv 528411 (2023). https:\/\/doi.org\/10.1101\/2023.02.13.528411.","DOI":"10.1101\/2023.02.13.528411"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62586"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04419-4"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14118-w"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2008523117"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12741"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2017.10.001"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.110887"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2627966100"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2008.03.002"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5438.300"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1514484112"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adg3032"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-020-07358-4"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01699-6"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.24.3083"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175279"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a841e4"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2022.05.005"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809818106"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1001145"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30470-2"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2711-0"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25960-2"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6202607"},{"key":"e_1_3_2_100_2","doi-asserted-by":"crossref","unstructured":"C. Voichita M. Donato S. Draghici \u201cIncorporating gene significance in the impact analysis of signaling pathways\u201d in 2012 11th International Conference on Machine Learning and Applications (IEEE 2012) vol. 1 pp. 126\u2013131.","DOI":"10.1109\/ICMLA.2012.230"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.22139.1"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.68605"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx760"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsigen.2020.102353"},{"key":"e_1_3_2_105_2","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giaa086"},{"key":"e_1_3_2_106_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes9090445"},{"key":"e_1_3_2_107_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_3_2_108_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_2_109_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr509"},{"key":"e_1_3_2_110_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1112s47"},{"key":"e_1_3_2_111_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00265-20"},{"key":"e_1_3_2_112_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14930"}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.adl3604","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T12:05:49Z","timestamp":1743768349000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.adl3604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,28]]},"references-count":111,"journal-issue":{"issue":"104","published-print":{"date-parts":[[2025,2,28]]}},"alternative-id":["10.1126\/sciimmunol.adl3604"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.adl3604","relation":{},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,28]]},"assertion":[{"value":"2023-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-17","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadl3604"}}