{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:49:53Z","timestamp":1789742993372,"version":"4.0.1"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,3,9]],"date-time":"2016-03-09T00:00:00Z","timestamp":1457481600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,3,9]],"date-time":"2016-03-09T00:00:00Z","timestamp":1457481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Mycobacterium avium<\/jats:italic> subsp. <jats:italic>paratuberculosis<\/jats:italic> (MAP) and Epstein-Barr virus (EBV) epitopes elicit a consistent humoral response in serum of multiple sclerosis patients, but the cross reactivity against the homologous myelin basic protein (MBP) and human interferon regulatory factor 5 (IRF5) has not been searched within the Cerebral Spinal Fluid (CSF). We evaluated in sera and CSF of patients with MS and with other neurological diseases (OND) the humoral response against EBV\/MAP peptides and the IRF5\/MBP. Our data showed that EBV and MAP peptides are able to induce a specific humoral immune response in MS patients compared to OND controls both in serum and in CSF. An intrathecal specific synthesis of IgG against MBP and their EBV and MAP homologous as indicated by the antibody index was observed in MS patients. The humoral response against EBV, MAP, MBP and IRF5 was significantly higher in MS patients compared to OND both in serum and in CSF. The higher presence of antibodies against MBP and their MAP and EBV homologous in CSF during relapses suggests a possible role of the pathogens in enhancing inflammation.<\/jats:p>","DOI":"10.1038\/srep22401","type":"journal-article","created":{"date-parts":[[2016,3,9]],"date-time":"2016-03-09T09:53:55Z","timestamp":1457517235000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Epstein Barr Virus and Mycobacterium avium subsp. paratuberculosis peptides are recognized in sera and cerebrospinal fluid of MS patients"],"prefix":"10.1038","volume":"6","author":[{"given":"Giuseppe","family":"Mameli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Cocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Frau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giovanna","family":"Marrosu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo Antonio","family":"Sechi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,9]]},"reference":[{"key":"BFsrep22401_CR1","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/ana.21117","volume":"61","author":"A Ascherio","year":"2007","unstructured":"Ascherio, A. & Munger, K. L. Environmental risk factors for multiple sclerosis. Part I: the role of the infection. Ann Neurol 61, 288\u2013299 (2007).","journal-title":"Ann Neurol"},{"key":"BFsrep22401_CR2","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jneuroim.2014.02.013","volume":"270","author":"G Mameli","year":"2014","unstructured":"Mameli, G. et al. Epstein-Barr virus and Mycobacterium avium subsp. paratuberculosis peptides are cross recognized by anti-myelin basic protein antibodies in multiple sclerosis patients. J Neuroimmunol 270, 51\u201355 (2014).","journal-title":"J Neuroimmunol"},{"key":"BFsrep22401_CR3","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1177\/1352458514557304","volume":"21","author":"D Cossu","year":"2015","unstructured":"Cossu, D. et al. Human interferon regulatory factor 5 homologous epitopes of Epstein-Barr virus and Mycobacterium avium subsp. paratuberculosisinduce a specific humoral and cellular immune response in multiple sclerosis patients. Multiple Sclerosis 21, 984\u2013995 (2015).","journal-title":"Multiple Sclerosis"},{"key":"BFsrep22401_CR4","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1155\/2006\/509476","volume":"22","author":"G Giovannoni","year":"2006","unstructured":"Giovannoni, G. Multiple sclerosis cerebrospinal fluid biomarkers. Dis Markers 22, 187\u2013196 (2006).","journal-title":"Dis Markers"},{"key":"BFsrep22401_CR5","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.4049\/jimmunol.180.2.1258","volume":"180","author":"A Belogurov Jr","year":"2008","unstructured":"Belogurov Jr, A. et al. Recognition and degradation of myelin basic protein peptides by serum autoantibodies: novel biomarker for multiple sclerosis. J Immunol 180, 1258\u20131267 (2008).","journal-title":"J Immunol"},{"key":"BFsrep22401_CR6","doi-asserted-by":"publisher","first-page":"3724","DOI":"10.1016\/j.febslet.2011.04.006","volume":"585","author":"K Kakalacheva","year":"2011","unstructured":"Kakalacheva, K. & L\u00fcnemann, J. D. Environmental triggers of multiple sclerosis. FEBS Lett 585, 3724\u20133729 (2011).","journal-title":"FEBS Lett"},{"key":"BFsrep22401_CR7","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1093\/clinchem\/37.7.1153","volume":"37","author":"H Reiber","year":"1991","unstructured":"Reiber, H. & Lange, P. Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clin Chem 37 (7), 1153\u20131160 (1991)","journal-title":"Clin Chem"},{"key":"BFsrep22401_CR8","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1128\/JCM.02532-05","volume":"44","author":"FC Westall","year":"2006","unstructured":"Westall, F. C. Molecular mimicry revisited: gut bacteria and multiple sclerosis. J Clin Microbiol 44, 2099\u20132104 (2006).","journal-title":"J Clin Microbiol"},{"key":"BFsrep22401_CR9","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1023\/A:1011064007686","volume":"21","author":"KC O\u2019Connor","year":"2001","unstructured":"O\u2019Connor, K. C., Bar-Or, A. & Hafler, D. A. The neuroimmunology of multiple sclerosis: possible roles of T and B lymphocytes in immunopathogenesis. J Clin Immunol 21, 81\u201392 (2001).","journal-title":"J Clin Immunol"},{"key":"BFsrep22401_CR10","doi-asserted-by":"publisher","first-page":"223","DOI":"10.2217\/fmb.12.135","volume":"8","author":"D Cossu","year":"2013","unstructured":"Cossu, D., Masala, S. & Sechi, L. A. A Sardinian map for multiple sclerosis. Future Microbiol 8, 223\u2013232 (2013).","journal-title":"Future Microbiol"},{"key":"BFsrep22401_CR11","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jns.2013.09.011","volume":"335","author":"D Cossu","year":"2013","unstructured":"Cossu, D. et al. Anti Mycobacterium avium subsp. paratuberculosis heat shock protein 70 antibodies in the sera of Sardinian patients with multiple sclerosis. J Neurol Sci 335, 131\u2013133 (2013).","journal-title":"J Neurol Sci"},{"key":"BFsrep22401_CR12","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1177\/1352458511433430","volume":"18","author":"D Cossu","year":"2012","unstructured":"Cossu, D. et al. Are Mycobacterium avium subsp. paratuberculosis and Epstein\u2013Barr virus triggers of multiple sclerosis in Sardinia? Mult Scler 18, 1181\u20131184 (2012).","journal-title":"Mult Scler"},{"key":"BFsrep22401_CR13","doi-asserted-by":"publisher","first-page":"96","DOI":"10.3389\/fimmu.2015.00096","volume":"6","author":"LA Sechi","year":"2015","unstructured":"Sechi, L. A. & Dow C. T. Mycobacterium avium ss. paratuberculosis Zoonosis - The Hundred Year War\u2013Beyond Crohn\u2019s Disease. Front Immunol 6, 96 (2015).","journal-title":"Front Immunol"},{"key":"BFsrep22401_CR14","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1177\/1352458508092353","volume":"14","author":"P Sundstr\u00f6m","year":"2008","unstructured":"Sundstr\u00f6m, P., Nystr\u00f6m, L., Jidell, E. & Hallmans, G. EBNA-1 reactivity and HLA DRB1*1501 as statistically independent risk factors for multiple sclerosis: a case-control study. Mult Scler 14, 1120\u20131122 (2008).","journal-title":"Mult Scler"},{"key":"BFsrep22401_CR15","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s12974-015-0353-1","volume":"12","author":"C Veroni","year":"2015","unstructured":"Veroni, C. et al. Immune and Epstein-Barr virus gene expression in cerebrospinal fluid and peripheral bloodmononuclear cells from patients with relapsing-remitting multiple sclerosis. J Neuroinflammation 12, 132 (2015).","journal-title":"J Neuroinflammation"},{"key":"BFsrep22401_CR16","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, 292\u2013302 (2011).","journal-title":"Ann Neurol"},{"key":"BFsrep22401_CR17","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.jneuroim.2013.07.017","volume":"15","author":"G Mameli","year":"2013","unstructured":"Mameli, G. et al. EBNA-1 IgG titers in Sardinian multiple sclerosis patients and controls. J Neuroimmunol 15, 120\u2013122 (2013).","journal-title":"J Neuroimmunol"},{"key":"BFsrep22401_CR18","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.molimm.2013.09.001","volume":"57","author":"D Cossu","year":"2014","unstructured":"Cossu, D. et al. Antigenic epitopes of MAP2694 homologous to T-cell receptor gamma-chain are highly recognize in multiple sclerosis Sardinia patients. Mol Immunol 57, 138\u2013140 (2014).","journal-title":"Mol Immunol"},{"key":"BFsrep22401_CR19","first-page":"99","volume":"4","author":"H Reiber","year":"1998","unstructured":"Reiber, H. Cerebrospinal fluid\u2013physiology, analysis and interpretation of protein patterns for diagnosis of neurological diseases. Mult Scler 4 (3), 99\u2013107 (1998).","journal-title":"Mult Scler"},{"key":"BFsrep22401_CR20","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.jneuroim.2007.04.002","volume":"187","author":"C Jacobi","year":"2007","unstructured":"Jacobi, C., Lange, P. & Reiber, H. Quantitation of intrathecal antibodies in cerebrospinal fluid of subacute sclerosing panencephalitis, herpes simplex encephalitis and multiple sclerosis: discrimination between microorganism-driven and polyspecific immune response. J Neuroimmunol 187, 139\u201346 (2007).","journal-title":"J Neuroimmunol"},{"key":"BFsrep22401_CR21","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1186\/s12974-014-0188-1","volume":"11","author":"M Castellazzi","year":"2014","unstructured":"Castellazzi, M. et al. Epstein-Barr virus-specific intrathecal oligoclonal IgG production in relapsing-remitting multiple sclerosis is limited to a subset of patients and is composed of low-affinity antibodies. J Neuroinflammation 11, 188 (2014).","journal-title":"J Neuroinflammation"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep22401.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep22401","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep22401.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T03:57:09Z","timestamp":1672891029000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep22401"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,9]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,3,21]]}},"alternative-id":["BFsrep22401"],"URL":"https:\/\/doi.org\/10.1038\/srep22401","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,9]]},"assertion":[{"value":"16 September 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22401"}}