Human Herpesvirus-6 (HHV-6) infection in multiple sclerosis: a preliminary report

Abstract

We examined cerebral spinal fluid (CSF) from multiple sclerosis (MS) patients and patients with other neurological diseases (OND) for antibody specific for Human Herpesvirus-6 (HHV-6) and for HHV-6 DNA detectable by PCR. CSF from MS patients had a higher frequency of IgG antibody to HHV-6 late antigens (39.4%) compared with CSF from OND (7.4%). In contrast, the frequency of detectable IgG antibody in CSF from MS patients specific for Epstein-Barr Virus (EBV) (12.1%) and Human Cytomegalovirus (HCMV) (6.1%) was much lower. Two of 12 MS CSFs (16.7%) also contained HHV-6 DNA detected by PCR. None of four OND CSF were positive for HHV-6 DNA. Plasma from 16 patients with MS, eight with OND and 72 healthy donors were tested for antibodies by ELISA to HHV-6 early (p41/38) and late (gp110) proteins. Although no differences in anti-gp110 IgG antibody were detected between MS patients, patients with other neurological diseases, and normals, IgG antibody to early protein p41/38 was detected in > 68% of the plasma from MS patients, 12.5% from OND patients and 27.8% of the controls. IgM antibody to p41/38 was present in > 56% of MS patients, 12.5% of OND patients, and 19% of controls. These data suggest that more than half of the MS patients had active, ongoing HHV-6 infections. HHV-6 was also isolated from peripheral blood mononuclear cells (PBMC) from 3/5 MS patients who were in relapse or had progressive disease and was identified as HHV-6 Variant B. These preliminary results support the hypothesis that HHV-6 may be a co-factor in the pathogenesis of some cases of MS.

Human Herpesvirus 6 Infection as a Trigger of Multiple Sclerosis

“…19,20 Two studies were classified as B quality. 24,25 Ongradi et al 24 reached statistical significance and reported only "high" and "low" antibody titers in MS patients and controls without providing actual values, whereas Ablashi et al 25 did not find significant differences in titers.…”

“…18,19 Four studies were classified as intermediate quality (B), and none of them showed a statistically significant difference between MS patients and controls. 20,[24][25][26] One of those studies considered mean antibody titers, 20 and another reported only that the IgG titers of MS patients were higher than those of controls without providing absolute values. 24 The remaining 7 studies were classified as lower quality (C), mostly because of a failure to define and provide details about the study patients with MS. [21][22][23]27,[29][30][31] According to the CTF classification, 18 of the 18 studies were classified as quality II-1.…”

“…Of the 18 studies presented (12 detecting CSF IgG antibodies and 6 CSF IgM antibodies), only 3 were classified as A quality and achieved statistical significance. 14,15,17 Another 3 were classified as A quality but did not achieve statistical significance 13,18 ( Three studies were classified as B quality and did not achieve statistical significance 24,25 (Ongradi et al 24 for both CSF IgG and IgM correlations).…”

“…The other available study was C quality and will not be discussed further. 25 A similar technique can be used to measure the immune response to specific antigens by incubating cultured PBMCs of patients or controls with the purified antigen of interest and then measuring the uptake of a radioactive tracer incorporated on the proliferating cells. This technique reportedly may be useful for evaluating the relationship between viral infection and recent MS onset.…”

“…Another 2 studies were classified as A quality. 18,49 Two studies classified as B quality achieved statistical significance, 25 All the aforementioned studies were classified as II-1 by the CTF classification criteria.…”