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Thus, we retrospectively characterized CSF and peripheral blood (PB) from 15 PRES patients, which we analyzed by multidimensional flow cytometry (FC). Results were compared to 72 controls, as well as to 9 patients with progressive multifocal leukoencephalopathy (PML, as a relevant differential diagnosis) and 15 multiple sclerosis patients (MS, as a classical neuroinflammatory disorder), respectively. Total protein level in CSF from PRES patients was elevated compared to that in controls, but not to MS and PML. In-depth FC analysis revealed no differences for adaptive immune cells (B cells, plasma cells, CD4<jats:sup>+<\/jats:sup>, and CD8<jats:sup>+<\/jats:sup> T cells) in PB or CSF of PRES compared to controls. In contrast, we observed alterations of the adaptive immune response in CSF of PML and MS compared to PRES, indicating that the adaptive immune response is not a driver of disease in PRES. Indeed, PRES was characterized by an innate immune response with CD14<jats:sup>++<\/jats:sup>\/CD16<jats:sup>+<\/jats:sup> (intermediate) monocytes elevated in PB and CSF, while CD14<jats:sup>++<\/jats:sup>\/CD16<jats:sup>\u2212<\/jats:sup> (classical) monocytes were decreased in PB from PRES patients as compared to controls. Levels of CD14<jats:sup>++<\/jats:sup>\/CD16<jats:sup>+<\/jats:sup> monocytes correlated with the duration of hospital stay as a surrogate marker for disease severity in PRES patients. Our findings argue for a role of innate rather than adaptive immunity in the pathophysiology of PRES. The observed shift in monocyte subsets might provide valuable diagnostic clues for the clinical management of these patients.<\/jats:p>","DOI":"10.1007\/s10875-021-01033-3","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T06:02:30Z","timestamp":1618207350000},"page":"1229-1240","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Innate Immune Response Characterizes Posterior Reversible Encephalopathy Syndrome"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6048-7143","authenticated-orcid":false,"given":"Christopher","family":"Nelke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schulte-Mecklenbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Pawlitzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leoni","family":"Rolfes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"R\u00e4uber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina C.","family":"Gross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Minnerup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Wiendl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Ruck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"issue":"6","key":"1033_CR1","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.3174\/ajnr.A0928","volume":"29","author":"WS Bartynski","year":"2008","unstructured":"Bartynski WS. 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Data were anonymized and collected retrospectively.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"CN, LR, SR, CCG, and JM declare no competing interests. ASM received research support and travel expenses from Novartis. MP received research support and travel expenses from Novartis. SGM received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS, and Teva. His research is funded by the German Ministry for Education and Research (BMBF), Bundesinstitut f\u00fcr Risikobewertung (BfR), Deutsche Forschungsgemeinschaft (DFG), Else Kr\u00f6ner Fresenius Foundation, Gemeinsamer Bundesausschuss (G-BA), German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology and by Alexion, Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, HERZ Burgdorf, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. HW received grants from the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Else Kr\u00f6ner Fresenius Foundation, Fresenius Foundation, the European Union, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster and RE Children\u2019s Foundation, Biogen, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme; consulting fees from Abbvie, Actelion, Biogen, IGES, Johnson & Johnson, Novartis, Roche, and Sanofi-Aventis; support for travel to meetings for other purposes from Abbvie, Actelion, Biogen, IGES, Johnson & Johnson, Novartis, Roche, and Sanofi-Aventis; fees for participation in review activities such as data monitoring boards from PSI CRO Deutschland GmbH and Swiss Multiple Sclerosis Society; payment for lectures from Alexion, Biogen, Cognomed, F. Hoffmann-La Roche Ltd., Gemeinn\u00fctzige Hertie-Stiftung, Merck Serono, Novartis, Roche Pharma AG, Genzyme, TEVA, and WebMD Global; and honorarium for expert testimony from Alexion, Biogen, Merck Serono, Novartis, and Genzyme outside the submitted work. He has filed patents No SEP-103.323-1\/08, EP2769223, WO2013057092 (A1), and 15001186.4 \u2013 1402. TR reports grants from the German Ministry of Education, Science, Research and Technology; grants and personal fees from Sanofi-Genzyme and Alexion; personal fees from Biogen, Roche, and Teva; and personal fees and nonfinancial support from Merck Serono, outside the submitted work.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}