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However, M, R and Z are only the most well-established constituents of a broader intrathecal humoral immune response in MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify additional anti-microbial antibodies inclusion of which in the classical MRZ panel may result in increased sensitivity without compromising the marker\u2019s high specificity for MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We determined the antibody indices (AIs) for 11 viral and bacterial agents (M, R, Z, herpes simplex virus, Epstein\u2013Barr virus, mumps virus, cytomegalovirus, parvovirus\u00a0B19,\n                      <jats:italic>Bordetella pertussis<\/jats:italic>\n                      ,\n                      <jats:italic>Corynebacterium diphtheriae,<\/jats:italic>\n                      and\n                      <jats:italic>Clostridium tetani<\/jats:italic>\n                      ) in paired\u00a0cerebrospinal fluid\u00a0and\u00a0serum samples\u00a0from patients with MS and disease controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A positive \u2018classical\u2019 MRZ reaction was found in 17\/26 (65.4%) MS patients. The five most frequently positive AIs among patients with MS were M (76.9%), Z (61.5%), R (57.7%), parvovirus\u00a0B19 (42.3%), and mumps (28%). Addition of parvovirus\u00a0B19 and mumps virus to the MRZ panel resulted in an increase in sensitivity in the MS group from 65.4% to 73.1%, with 22% of the initially MRZ-negative patients exhibiting a de novo-positive response. The extended MRZ panel (\u2018MRZ\n                      <jats:italic>plus<\/jats:italic>\n                      \u2019) distinguished sharply between MS (\u2265\u20093 AIs in 90% of all positives) and controls (varying diagnoses, from migraine to vasculitis;\u00a00-1 AIs;\n                      <jats:italic>p\u2009<\/jats:italic>\n                      &lt;\u20090.000001). The highest median AI in the MS group was found for parvovirus\u00a0B19 (3.97), followed by measles virus (2.79).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inclusion of parvovirus\u00a0B19 and mumps virus\u00a0in the test panel resulted in an increase in the sensitivity and discriminatory power of MRZ. Our results provide a strong rational for prospective studies investigating the role of extended MRZ panels in the differential diagnosis of MS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-021-10471-3","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T07:02:51Z","timestamp":1616742171000},"page":"3758-3765","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Parvovirus B19 and mumps virus antibodies are major constituents of the intrathecal immune response in European patients with MS and increase the diagnostic sensitivity and discriminatory power of the MRZ reaction"],"prefix":"10.1007","volume":"268","author":[{"given":"S.","family":"Jarius","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Wilken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Haas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Ruprecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Komorowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Wildemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"10471_CR1","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/j.1600-0404.2005.00418.x","volume":"112","author":"J Bednarova","year":"2005","unstructured":"Bednarova J, Stourac P, Adam P (2005) Relevance of immunological variables in neuroborreliosis and multiple sclerosis. 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Diana Wilken and Lars Komorowski are employees of Euroimmun AG, L\u00fcbeck, Germany. Klemens Ruprecht received research support from Novartis, Merck Serono, German Ministry of Education and Research, European Union (821283-2), Stiftung Charit\u00e9 (BIH Clinical Fellow Program) and Arthur Arnstein Foundation; received speaker honoraria and travel grants from Bayer, Biogen Idec, Merck Serono, sanofi-aventis\/Genzyme, Teva, Roche, Novartis, and Guthy Jackson Charitable Foundation, none of which are related to the present study. Brigitte Wildemann received grants from German Ministry of Education and Research, Deutsche Forschungsgemeinschaft, Dietmar Hopp Foundation, and Klaus Tschira Foundation, grants and personal fees from Merck Serono, Sanofi Genzyme, and Novartis pharmaceuticals, and personal fees from Bayer Healthcare, Biogen, Teva Pharma, none of which are related to the present study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}