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. 2012;7(7):e40431.
doi: 10.1371/journal.pone.0040431. Epub 2012 Jul 9.

Intrathecal, polyspecific antiviral immune response in oligoclonal band negative multiple sclerosis

Isabel Brecht  1 , Benedikt Weissbrich, Julia Braun, Klaus Viktor Toyka, Andreas Weishaupt, Mathias Buttmann
Affiliations

Intrathecal, polyspecific antiviral immune response in oligoclonal band negative multiple sclerosis

Isabel Brecht et al. PLoS One. 2012.

Abstract

Background: Oligoclonal bands (OCB) are detected in the cerebrospinal fluid (CSF) in more than 95% of patients with multiple sclerosis (MS) in the Western hemisphere. Here we evaluated the intrathecal, polyspecific antiviral immune response as a potential diagnostic CSF marker for OCB-negative MS patients.

Methodology/principal findings: We tested 46 OCB-negative German patients with paraclinically well defined, definite MS. Sixteen OCB-negative patients with a clear diagnosis of other autoimmune CNS disorders and 37 neurological patients without evidence for autoimmune CNS inflammation served as control groups. Antibodies against measles, rubella, varicella zoster and herpes simplex virus in paired serum and CSF samples were determined by ELISA, and virus-specific immunoglobulin G antibody indices were calculated. An intrathecal antibody synthesis against at least one neurotropic virus was detected in 8 of 26 (31%) patients with relapsing-remitting MS, 8 of 12 (67%) with secondary progressive MS and 5 of 8 (63%) with primary progressive MS, in 3 of 16 (19%) CNS autoimmune and 3 of 37 (8%) non-autoimmune control patients. Antibody synthesis against two or more viruses was found in 11 of 46 (24%) MS patients but in neither of the two control groups. On average, MS patients with a positive antiviral immune response were older and had a longer disease duration than those without.

Conclusion: Determination of the intrathecal, polyspecific antiviral immune response may allow to establish a CSF-supported diagnosis of MS in OCB-negative patients when two or more of the four virus antibody indices are elevated.

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Conflict of interest statement

Competing Interests: This study was partially funded by Merck Serono Germany. None of the authors nor Merck Serono has commercial interests related to the content of this manuscript. I.B. received a travel grant from Merck Serono. B.W. received research grants from Abbott, Dade Behring and Siemens, and lecture fees from Dade Behring. J.B. reports no disclosures. K.V.T. served on a scientific advisory board for Merck Serono; has received travel expenses and/or speaker honoraria from Lundbeck Inc. and Teva Pharmaceutical Industries Ltd., and for lectures or educational activities not funded by industry; serves on the editorial boards of Current Treatment Options in Neurology and Therapeutic Advances in Neurological Disorders; serves as a consultant to Teva Pharmaceutical Industries Ltd., and served as a consultant to Merck Serono and Ebewe Neuro Pharma GmbH; and received research support from Sanofi Aventis and Teva Pharmaceutical Industries Ltd., Merck Serono, the DFG (German National Research Foundation), the BMBF (German Federal Ministry of Education and Science), State of Bavaria Research Funds, University Research Funds, the Gemeinnützige Hertie Stiftung, and the German MS Society Research Fund. A.W. received research grants from the Interdisciplinary Center for Clinical Research (IZKF) at the University of Würzburg and from the Gemeinnützige Hertie Stiftung. M.B. received a travel grant from Biogen Idec; travel grants, speaker’s fees and a research grant from Merck Serono; served on an advisory board for Almirall Hermal GmbH; and received research grants from Sanofi Aventis and Teva Pharmaceutical Industries Ltd., Novartis, and the Interdisciplinary Center for Clinical Research (IZKF) at the University of Würzburg. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Antibody indices (AI) for the indicated viruses in control and MS patients.
Dots represent individual values, lines reflect median values. AI was defined as 0, when virus antibodies were not detectable (n = 50 of 396). The dotted line reflects the upper limit of the normal range (1.4 [3]). Statistics: Kruskal-Wallis test for each virus AI, followed by Dunn’s multiple comparison test. P values of <0.05 were defined as statistically significant. Abbreviations: see Table 2.
Figure 2
Figure 2. Correlation of age and disease duration with the intrathecal antiviral immune response.
Multiple sclerosis patients (n = 46) were grouped according to the number of elevated AIs and analyzed for age (A) and disease duration (B) at the time of spinal tap. Dots represent individual values for age (A) and duration (B), lines reflect median values. Statistics: Kruskal-Wallis test followed by Dunn’s multiple comparison test. P values of <0.05 were defined as statistically significant.
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