{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T18:38:04Z","timestamp":1782758284259,"version":"3.54.5"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T00:00:00Z","timestamp":1606262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1279, SFB TR128"],"award-info":[{"award-number":["SFB 1279, SFB TR128"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The MRZ reaction (MRZR) comprises the three antibody indices (AIs) against measles, rubella, and varicella zoster virus, reflecting an intrathecal polyspecific B cell response highly specific for multiple sclerosis (MS). Thus, MRZR can be used to confirm a diagnosis of primary progressive MS (PPMS) but its pathophysiological and wider clinical relevance is unclear. This study aimed to investigate whether PPMS patients with a positive MRZR (MRZR+) differ from those with a negative MRZR (MRZR-) according to cerebrospinal fluid (CSF) biomarkers of B cell activity, neuroaxonal damage or glial activity, and clinical features. (1) Methods: In a multicenter PPMS cohort (n = 81) with known MRZR status, we measured B cell-activating factor (BAFF), chemokine CXC ligand 13 (CXCL-13), soluble B cell maturation antigen (sBCMA), soluble transmembrane activator and CAML interactor (sTACI), and chitinase-3-like protein 1 (CHI3L1) in the CSF with enzyme-linked immunosorbent assays (ELISAs). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were detected in serum and CSF using single molecule array (SIMOA) technology. (2) Results: MRZR+ patients (45.7% of all PPMS patients) revealed higher levels of NfL in CSF compared to MRZR- patients (54.3%). There were positive correlations between each of sBCMA, sTACI, and intrathecal immunoglobin G (IgG) synthesis. Additionally, NfL concentrations in serum positively correlated with those in CSF and those of GFAP in serum. However, MRZR+ and MRZR- patients did not differ concerning clinical features (e.g., age, disease duration, Expanded Disability Status Scale (EDSS) at diagnosis and follow-up); CSF routine parameters; CSF concentrations of BAFF, CXCL-13, sBCMA, sTACI, CHI3L1, and GFAP; or serum concentrations of GFAP and NfL. (3) Conclusions: In PPMS patients, MRZR positivity might indicate a more pronounced axonal damage. Higher levels of the soluble B cell receptors BCMA and transmembrane activator and CAML interactor (TACI) in CSF are associated with a stronger intrathecal IgG synthesis in PPMS.<\/jats:p>","DOI":"10.3390\/cells9122543","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T21:55:06Z","timestamp":1606341306000},"page":"2543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cerebrospinal Fluid Biomarkers in Relation to MRZ Reaction Status in Primary Progressive Multiple Sclerosis"],"prefix":"10.3390","volume":"9","author":[{"given":"Tilman","family":"Robinson","sequence":"first","affiliation":[{"name":"Clinic of Neurology and Neurophysiology, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79085 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Abdelhak","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1151-1140","authenticated-orcid":false,"given":"Tanima","family":"Bose","sequence":"additional","affiliation":[{"name":"Biomedical Center and Klinikum Grosshadern, Institute of Clinical Neuroimmunology, Ludwig Maximilian University, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Meinl","sequence":"additional","affiliation":[{"name":"Biomedical Center and Klinikum Grosshadern, Institute of Clinical Neuroimmunology, Ludwig Maximilian University, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4273-4267","authenticated-orcid":false,"given":"Markus","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe K.","family":"Zettl","sequence":"additional","affiliation":[{"name":"Neuroimmunological Section, Department of Neurology, Medical Center of the University of Rostock, 18051 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick","family":"Dersch","sequence":"additional","affiliation":[{"name":"Clinic of Neurology and Neurophysiology, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79085 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayrettin","family":"Tumani","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Ulm, 89081 Ulm, Germany"},{"name":"Specialty Hospital Dietenbronn, 88477 Schwendi, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Rauer","sequence":"additional","affiliation":[{"name":"Clinic of Neurology and Neurophysiology, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79085 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2761-7591","authenticated-orcid":false,"given":"Andr\u00e9","family":"Huss","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00401-012-0953-0","article-title":"Primary progressive multiple sclerosis: Part of the MS disease spectrum or separate disease entity?","volume":"123","author":"Antel","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1212\/WNL.46.4.907","article-title":"Defining the clinical course of multiple sclerosis: Results of an international survey","volume":"46","author":"Lublin","year":"1996","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S1474-4422(07)70243-0","article-title":"Primary-progressive multiple sclerosis","volume":"6","author":"Miller","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1179\/016164106X98099","article-title":"The B cell response in multiple sclerosis","volume":"28","author":"Owens","year":"2006","journal-title":"Neurol. 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