{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:10:52Z","timestamp":1792714252468,"version":"4.5.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["20FC1030"],"award-info":[{"award-number":["20FC1030"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K07892"],"award-info":[{"award-number":["20K07892"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system; however, its exact mechanism is unknown. This study aimed to elucidate the profile of white blood cells (WBCs) in the acute phase of an MS attack. Sixty-four patients with MS at the time of diagnosis and 2492 age- and sex-adjusted healthy controls (HCs) were enrolled. Data regarding the blood cell counts were compared between the groups. The total WBC (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), monocyte (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), basophil (<jats:italic>p<\/jats:italic>\u2009=\u20090.0027), and neutrophil (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) counts were higher in the MS group than in the HC group, whereas the lymphocyte and eosinophil counts did not differ. Adjustments for the smoking status and body mass index yielded the same results. The total and differential WBC counts of the patients with MS did not correlate with the counts of T2 hyperintense brain lesions or the levels of neurological disturbance. In summary, patients with MS showed elevated counts of total WBCs, monocytes, basophils, and neutrophils at the time of diagnosis. However, the clinical relevance of these biomarkers in the context of the development and progression of MS remains unclear.<\/jats:p>","DOI":"10.1038\/s41598-021-01942-8","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T11:06:37Z","timestamp":1637060797000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["White blood cell count profiles in multiple sclerosis during attacks before the initiation of acute and chronic treatments"],"prefix":"10.1038","volume":"11","author":[{"given":"Tetsuya","family":"Akaishi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Misu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Fujihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Nakaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mana","family":"Kogure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rieko","family":"Hatanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumi","family":"Itabashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikumi","family":"Kanno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kuroda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juichi","family":"Fujimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Takai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimihiko","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Hozawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"issue":"3","key":"1942_CR1","doi-asserted-by":"publisher","first-page":"a028936","DOI":"10.1101\/cshperspect.a028936","volume":"8","author":"H Lassmann","year":"2018","unstructured":"Lassmann, H. Multiple sclerosis pathology. Cold Spring Harb. Perspect. Med. 8(3), a028936 (2018).","journal-title":"Cold Spring Harb. Perspect. Med."},{"issue":"3\u20134","key":"1942_CR2","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1159\/000360528","volume":"72","author":"CP Kamm","year":"2014","unstructured":"Kamm, C. P., Uitdehaag, B. M. & Polman, C. H. Multiple sclerosis: Current knowledge and future outlook. Eur. Neurol. 72(3\u20134), 132\u2013141 (2014).","journal-title":"Eur. Neurol."},{"issue":"2","key":"1942_CR3","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","volume":"17","author":"AJ Thompson","year":"2018","unstructured":"Thompson, A. J. et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 17(2), 162\u2013173 (2018).","journal-title":"Lancet Neurol."},{"issue":"4","key":"1942_CR4","first-page":"205521731881318","volume":"4","author":"IC Hasselbalch","year":"2018","unstructured":"Hasselbalch, I. C. et al. The neutrophil-to-lymphocyte ratio is associated with multiple sclerosis. Mult. Scler. J. Exp. Transl. Clin. 4(4), 2055217318813183 (2018).","journal-title":"Mult. Scler. J. Exp. Transl. Clin."},{"key":"1942_CR5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.msard.2017.10.009","volume":"18","author":"AK Bisgaard","year":"2017","unstructured":"Bisgaard, A. K., Pihl-Jensen, G. & Frederiksen, J. L. The neutrophil-to-lymphocyte ratio as disease activity marker in multiple sclerosis and optic neuritis. Mult. Scler. Relat. Disord. 18, 213\u2013217 (2017).","journal-title":"Mult. Scler. Relat. Disord."},{"issue":"8","key":"1942_CR6","first-page":"700","volume":"126","author":"S Demirci","year":"2016","unstructured":"Demirci, S., Demirci, S., Kutluhan, S., Koyuncuoglu, H. R. & Yurekli, V. A. The clinical significance of the neutrophil-to-lymphocyte ratio in multiple sclerosis. Int. J. Neurosci. 126(8), 700\u2013706 (2016).","journal-title":"Int. J. Neurosci."},{"issue":"1","key":"1942_CR7","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s12883-019-1245-2","volume":"19","author":"CC Hemond","year":"2019","unstructured":"Hemond, C. C., Glanz, B. I., Bakshi, R., Chitnis, T. & Healy, B. C. The neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios are independently associated with neurological disability and brain atrophy in multiple sclerosis. BMC Neurol. 19(1), 23 (2019).","journal-title":"BMC Neurol."},{"issue":"3","key":"1942_CR8","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s00441-017-2753-2","volume":"371","author":"K Prame Kumar","year":"2018","unstructured":"Prame Kumar, K., Nicholls, A. J. & Wong, C. H. Y. Partners in crime: neutrophils and monocytes\/macrophages in inflammation and disease. Cell Tissue Res. 371(3), 551\u2013565 (2018).","journal-title":"Cell Tissue Res."},{"issue":"4","key":"1942_CR9","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1080\/21645515.2017.1417711","volume":"14","author":"S Chirumbolo","year":"2018","unstructured":"Chirumbolo, S., Bj\u00f8rklund, G., Sboarina, A. & Vella, A. The role of basophils as innate immune regulatory cells in allergy and immunotherapy. Hum. Vaccin. Immunother. 14(4), 815\u2013831 (2018).","journal-title":"Hum. Vaccin. Immunother."},{"issue":"2","key":"1942_CR10","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/ana.22366","volume":"69","author":"CH Polman","year":"2011","unstructured":"Polman, C. H. et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann. Neurol. 69(2), 292\u2013302 (2011).","journal-title":"Ann. Neurol."},{"issue":"1","key":"1942_CR11","doi-asserted-by":"publisher","first-page":"65","DOI":"10.2188\/jea.JE20190271","volume":"31","author":"A Hozawa","year":"2021","unstructured":"Hozawa, A. et al. Study profile of the Tohoku Medical Megabank Community-Based Cohort Study. J. Epidemiol. 31(1), 65\u201376 (2021).","journal-title":"J. Epidemiol."},{"issue":"9","key":"1942_CR12","doi-asserted-by":"publisher","first-page":"493","DOI":"10.2188\/jea.JE20150268","volume":"26","author":"S Kuriyama","year":"2016","unstructured":"Kuriyama, S. et al. The Tohoku Medical Megabank Project: Design and mission. J. Epidemiol. 26(9), 493\u2013511 (2016).","journal-title":"J. Epidemiol."},{"issue":"3","key":"1942_CR13","doi-asserted-by":"publisher","first-page":"e0121945","DOI":"10.1371\/journal.pone.0121945","volume":"10","author":"B Diedenhofen","year":"2015","unstructured":"Diedenhofen, B. & Musch, J. cocor: a comprehensive solution for the statistical comparison of correlations. PLoS ONE 10(3), e0121945 (2015).","journal-title":"PLoS ONE"},{"issue":"1","key":"1942_CR14","doi-asserted-by":"publisher","first-page":"e6","DOI":"10.1016\/j.jinf.2020.04.002","volume":"81","author":"Y Liu","year":"2020","unstructured":"Liu, Y. et al. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J. Infect. 81(1), e6\u2013e12 (2020).","journal-title":"J. Infect."},{"issue":"7","key":"1942_CR15","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/j.jstrokecerebrovasdis.2013.01.011","volume":"22","author":"S Tokgoz","year":"2013","unstructured":"Tokgoz, S. et al. Neutrophil lymphocyte ratio as a predictor of stroke. J. Stroke Cerebrovasc. Dis. 22(7), 1169\u20131174 (2013).","journal-title":"J. Stroke Cerebrovasc. Dis."},{"issue":"2","key":"1942_CR16","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1159\/000341583","volume":"34","author":"ME Kuyumcu","year":"2012","unstructured":"Kuyumcu, M. E. et al. The evaluation of neutrophil-lymphocyte ratio in Alzheimer\u2019s disease. Dement. Geriatr. Cogn. Disord. 34(2), 69\u201374 (2012).","journal-title":"Dement. Geriatr. Cogn. Disord."},{"issue":"3","key":"1942_CR17","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s10072-014-1976-1","volume":"36","author":"E Ak\u0131l","year":"2015","unstructured":"Ak\u0131l, E. et al. The increase of carcinoembryonic antigen (CEA), high-sensitivity C-reactive protein, and neutrophil\/lymphocyte ratio in Parkinson\u2019s disease. Neurol. Sci. 36(3), 423\u2013428 (2015).","journal-title":"Neurol. Sci."},{"issue":"1","key":"1942_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000026552","volume":"39","author":"M Maes","year":"1999","unstructured":"Maes, M. et al. The effects of psychological stress on leukocyte subset distribution in humans: evidence of immune activation. Neuropsychobiology 39(1), 1\u20139 (1999).","journal-title":"Neuropsychobiology"},{"issue":"6","key":"1942_CR19","doi-asserted-by":"publisher","first-page":"531","DOI":"10.2486\/indhealth.2013-0045","volume":"52","author":"N Nishitani","year":"2014","unstructured":"Nishitani, N. & Sakakibara, H. Association of psychological stress response of fatigue with white blood cell count in male daytime workers. Ind. Health 52(6), 531\u2013534 (2014).","journal-title":"Ind. Health"},{"issue":"1","key":"1942_CR20","doi-asserted-by":"publisher","first-page":"121","DOI":"10.4306\/pi.2016.13.1.121","volume":"13","author":"E Aydin Sunbul","year":"2016","unstructured":"Aydin Sunbul, E. et al. Increased neutrophil\/lymphocyte ratio in patients with depression is correlated with the severity of depression and cardiovascular risk factors. Psychiatry Investig. 13(1), 121\u2013126 (2016).","journal-title":"Psychiatry Investig."},{"key":"1942_CR21","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.clim.2016.06.017","volume":"189","author":"ER Pierson","year":"2018","unstructured":"Pierson, E. R., Wagner, C. A. & Goverman, J. M. The contribution of neutrophils to CNS autoimmunity. Clin. Immunol. 189, 23\u201328 (2018).","journal-title":"Clin. Immunol."},{"issue":"1\u20132","key":"1942_CR22","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.jneuroim.2011.11.009","volume":"242","author":"M Naegele","year":"2012","unstructured":"Naegele, M. et al. Neutrophils in multiple sclerosis are characterized by a primed phenotype. J. Neuroimmunol. 242(1\u20132), 60\u201371 (2012).","journal-title":"J. Neuroimmunol."},{"issue":"1","key":"1942_CR23","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1177\/1352458510379243","volume":"17","author":"J Mikita","year":"2011","unstructured":"Mikita, J. et al. Altered M1\/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration. Mult. Scler. 17(1), 2\u201315 (2011).","journal-title":"Mult. Scler."},{"key":"1942_CR24","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jneuroim.2018.03.016","volume":"319","author":"T Akaishi","year":"2018","unstructured":"Akaishi, T., Takahashi, T. & Nakashima, I. Peripheral blood monocyte count at onset may affect the prognosis in multiple sclerosis. J. Neuroimmunol. 319, 37\u201340 (2018).","journal-title":"J. Neuroimmunol."},{"issue":"3","key":"1942_CR25","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.alit.2017.04.007","volume":"66","author":"K Miyake","year":"2017","unstructured":"Miyake, K. & Karasuyama, H. Emerging roles of basophils in allergic inflammation. Allergol. Int. 66(3), 382\u2013391 (2017).","journal-title":"Allergol. Int."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-01942-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-01942-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-01942-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T17:23:20Z","timestamp":1670088200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-01942-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,16]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["1942"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-01942-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,16]]},"assertion":[{"value":"3 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"K. Fujihara received speaker honoraria and travel funding from Bayer, Biogen Japan, Eisai, Mitsubishi Tanabe, Novartis, Astellas, Takeda, Asahi Kasei Medical, Daiichi Sankyo, and Nihon Pharmaceutical and received research support from Bayer, Biogen, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva, Mitsubishi Tanabe Pharma, Teijin, Chugai, Ono, Nihon Pharmaceutical, and Genzyme. I. Nakashima received speaker honoraria and travel funding from Mitsubishi Tanabe Pharma, Biogen Japan, and Novartis Pharmaceuticals and received research support from LSI Medience Corporation. The remaining authors don\u2019t have any conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22357"}}