{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:05:07Z","timestamp":1791389107044,"version":"4.3.3"},"reference-count":58,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,4,26]],"date-time":"2020-04-26T00:00:00Z","timestamp":1587859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000381","name":"Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["747\/02"],"award-info":[{"award-number":["747\/02"]}],"id":[{"id":"10.13039\/501100000381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0700356"],"award-info":[{"award-number":["G0700356"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008659","name":"European Committee for Treatment and Research in Multiple Sclerosis","doi-asserted-by":"publisher","award":["Fellowship"],"award-info":[{"award-number":["Fellowship"]}],"id":[{"id":"10.13039\/100008659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Increased inflammation in the cerebral meninges is associated with extensive subpial cortical grey matter pathology in the forebrain and a more severe disease course in a substantial proportion of secondary progressive multiple sclerosis (SPMS) cases. It is not known whether this relationship extends to spinal cord pathology. We assessed the contribution of meningeal and parenchymal immune infiltrates to spinal cord pathology in SPMS cases characterized in the presence (F+) or absence (F\u2212) of lymphoid\u2010like structures in the forebrain meninges. Transverse cryosections of cervical, thoracic and lumbar cord of 22 SPMS and five control cases were analyzed for CD20+ B cells, CD4+ and CD8+ T cells, microglia\/macrophages (IBA\u20101+), demyelination (myelin oligodendrocyte glycoprotein+) and axon density (neurofilament\u2010H+). Lymphoid\u2010like structures containing follicular dendritic cell networks and dividing B cells were seen in the spinal meninges of 3 out of 11 F+\u00a0SPMS cases. CD4+ and CD20+ cell counts were increased in F+\u00a0SPMS compared to F\u2212\u00a0SPMS and controls, whilst axon loss was greatest in motor and sensory tracts of the F+\u00a0SPMS cases (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). The density of CD20+ B cells of the spinal leptomeninges correlated with CD4+ T cells and total B and T cells of the meninges; with the density of white matter perivascular CD20+ and CD4+ lymphocytes (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05); with white matter lesion area (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05); and the extent of axon loss (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) in F+\u00a0SPMS cases only. We show that the presence of lymphoid\u2010like structures in the forebrain is associated with a profound spinal cord pathology and local B cell rich meningeal inflammation associates with the extent of cord pathology. Our work supports a principal role for B cells in sustaining inflammation and tissue injury throughout the CNS in the progressive disease stage.<\/jats:p>","DOI":"10.1111\/bpa.12841","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T15:36:39Z","timestamp":1585928199000},"page":"779-793","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":126,"title":["B cell rich meningeal inflammation associates with increased spinal cord pathology in multiple sclerosis"],"prefix":"10.1111","volume":"30","author":[{"given":"Camilla","family":"Reali","sequence":"first","affiliation":[{"name":"Department of Brain Sciences Faculty of Medicine Imperial College London UK"},{"name":"Merck Healthcare KGaA Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Magliozzi","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences Faculty of Medicine Imperial College London UK"},{"name":"Department of Neuroscience, Biomedicine and Movement University of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Roncaroli","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences Faculty of Medicine Imperial College London UK"},{"name":"Division of Neuroscience and Experimental Psychology Faculty of Biology, Medicine and Health University of Manchester Manchester UK"},{"name":"Manchester Academic Health Science Centre Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Nicholas","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences Faculty of Medicine Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-9157","authenticated-orcid":false,"given":"Owain W.","family":"Howell","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences Faculty of Medicine Imperial College London UK"},{"name":"Institute for Life Sciences Swansea University Medical School Swansea UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences Faculty of Medicine Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq223"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22054"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.01.042"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21939"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111675"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25365"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200012)48:6<893::AID-ANA10>3.0.CO;2-B"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww296"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458516663034"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3900"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws189"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt031"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707731105"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl074"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.10.6092"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh323"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp070"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt279"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2006.00018.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2008.00228.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.445"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv398"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1601277"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr182"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12199"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.011"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24408"},{"key":"e_1_2_10_29_1","first-page":"1","article-title":"Pathogenic mechanisms associated with different clinical courses of multiple sclerosis","volume":"10","author":"Lassmann H","year":"2019","journal-title":"Front Immunol"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0135-x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aab4176"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2012.02.015"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2017.05.004"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.2.308"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq350"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1100648"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy151"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1650-x"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25197"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22230"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm038"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv011"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130699"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606468"},{"key":"e_1_2_10_45_1","volume-title":"When to choose a nonparametric test","author":"Motulsky HJ"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.4239"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09614"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31820d8b1d"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12516"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0840-0"},{"key":"e_1_2_10_51_1","first-page":"12","article-title":"Improving reporting of multiple sclerosis relapse","volume":"111","author":"Roberts M","year":"2015","journal-title":"Nurs Times"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514522537"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21799"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.01.052"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2004.tb00049.x"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3794-09.2009"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458510364992"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21719"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12165"}],"container-title":["Brain Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbpa.12841","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.12841","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bpa.12841","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.12841","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T11:09:37Z","timestamp":1693912177000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bpa.12841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,26]]},"references-count":58,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1111\/bpa.12841"],"URL":"https:\/\/doi.org\/10.1111\/bpa.12841","archive":["Portico"],"relation":{},"ISSN":["1015-6305","1750-3639"],"issn-type":[{"value":"1015-6305","type":"print"},{"value":"1750-3639","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,26]]},"assertion":[{"value":"2019-10-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}