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The Correlation between the Virus- and Brain Antigen-Specific B Cell Response in the Blood of Patients with Multiple Sclerosis

Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany
Department of Anatomy I, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany
Cellular Technology Limited, 20521 Chagrin Blvd, Shaker Heights, OH 44122, USA
Department of Neurology, University Hospitals of Cologne, Kerpener Straße 62, 50937 Cologne, Germany
Department of Neurology, Klinikum Augsburg, Stenglinstraße 2, 86156 Augsburg, Germany
Department of Neurology, Caritas-Krankenhaus Bad Mergentheim, Uhlandstraße 7, 97980 Bad Mergentheim, Germany
Author to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Viruses 2016, 8(4), 105;
Received: 10 March 2016 / Revised: 5 April 2016 / Accepted: 12 April 2016 / Published: 23 April 2016
PDF [3113 KB, uploaded 23 April 2016]


There is a largely divergent body of literature regarding the relationship between Epstein-Barr virus (EBV) infection and brain inflammation in multiple sclerosis (MS). Here, we tested MS patients during relapse (n = 11) and in remission (n = 19) in addition to n = 22 healthy controls to study the correlation between the EBV- and brain-specific B cell response in the blood by enzyme-linked immunospot (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). Cytomegalovirus (CMV) was used as a control antigen tested in n = 16 MS patients during relapse and in n = 35 patients in remission. Over the course of the study, n = 16 patients were untreated, while n = 33 patients received immunomodulatory therapy. The data show that there was a moderate correlation between the frequencies of EBV- and brain-reactive B cells in MS patients in remission. In addition we could detect a correlation between the B cell response to EBV and disease activity. There was no evidence of an EBV reactivation. Interestingly, there was also a correlation between the frequencies of CMV- and brain-specific B cells in MS patients experiencing an acute relapse and an elevated B cell response to CMV was associated with higher disease activity. The trend remained when excluding seronegative subjects but was non-significant. These data underline that viral infections might impact the immunopathology of MS, but the exact link between the two entities remains subject of controversy. View Full-Text
Keywords: B cells; CMV; EBV; ELISPOT; MS B cells; CMV; EBV; ELISPOT; MS

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Wunsch, M.; Hohmann, C.; Milles, B.; Rostermund, C.; Lehmann, P.V.; Schroeter, M.; Bayas, A.; Ulzheimer, J.; Mäurer, M.; Ergün, S.; Kuerten, S. The Correlation between the Virus- and Brain Antigen-Specific B Cell Response in the Blood of Patients with Multiple Sclerosis. Viruses 2016, 8, 105.

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