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

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.

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. 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.