Correlation between HHV‐6 reactivation and multiple sclerosis disease activity

Abstract

This study examined the association between HHV-6 infection and multiple sclerosis (MS) and the relationship between HHV-6 reactivation and disease activity. The frequency of HHV-6 genomic sequences in peripheral blood mononuclear cells (PBMCs), the incidence of plasma viremia (nPCR), the transcription of viral mRNA in PBMCs (RT-PCR), the presence of antiviral IgM and IgG class antibodies in the plasma (IFA) of 16 relapsing/remitting and secondary progressive MS patients were studied in comparison with clinical manifestations of the disease, magnetic resonance imaging (MRI) of brain, and serum interleukin (IL)-12 concentrations (ELISA). The prevalence of HHV-6 infection was significantly higher in patients with MS (16/26) than in patients with other neurological diseases (6/21) and in blood donors (43/150). HHV-6 reactivation was found during periods of disease activity with Gadolinium-enhancing lesions on MRI in both relapsing/remitting and secondary progressive MS (10/13; 76.9%). In patients with active MS disease, serum concentrations of IL-12 were significantly higher in those patients with active HHV-6 infection than in patients with latent infection. The data confirm an association between HHV-6 infection and MS and show a correlation between HHV-6 reactivation and disease activity in relapsing/remitting and secondary progressive MS. The risk of an exacerbation of MS was significantly higher (P < 0.005) in patients with active HHV-6 infection than in patients with latent infection. A clear correlation between HHV-6 reactivation and serum IL-12 concentrations during disease activity has been demonstrated. The results suggest that HHV-6 reactivation is implicated in exacerbation of MS, possibly through modulation of IL-12 synthesis.

Mini review article. Human herpesvirus-6 and the etiology of multiple sclerosis: a literature review

“…The presence of viral DNA in serum/plasma has been used as a marker for active viral infection [29][30]. The herpesviruses have DNA genomes and because they need to infect cells for replication, extracellular viral DNA most probably denotes assembled virions, liberated from cells for further Human herpesvirus-6 in multiple sclerosis infection.…”

Human Herpesvirus 6 Infection as a Trigger of Multiple Sclerosis

“…Four studies found a statistically significant difference between the proportion of MS patients who had anti-HHV-6 serum IgG antibodies compared with controls and were classified as high quality (A). 14, 15,17,28 Four studies were classified as A quality but did not reach statistical significance. 13,16,18,19 Of those 4 studies, 2 considered mean antibody titers rather than an arbitrary positive titer.…”

“…CSF of MS patients than in that of controls, a finding supporting the correlation between HHV-6 infection and MS. 14, 15,17 The 2 main considerations/limitations in reviewing CSF studies are whether the CSF examined was whole or fractionated (in the case of an acellular CSF sample, a positive result is more likely to derive from the central nervous system rather than from peripheral immune cells) and whether, as was often the case, control CSF samples were obtained from patients with other neurologic diseases rather than from healthy controls. Thus, CSF samples were usually selected on the basis of availability rather than from a carefully selected control matched to an MS patient.…”

“…One study was classified as A quality and had statistically significant results between MS patients and controls. 17 Another 6 studies were classified as A quality but did not reach statistical significance. 18,36,38,39,41,49 Two of those studies did not present any HHV-6-positive patients or controls.…”

“…Two studies reported statistically significant differences between MS patients and controls and were classified as A quality. 17,37 Alvarez-Lafuente et al 37 presented DNA prevalence rather than total values and distinguished between high and low values. Another 2 studies were classified as A quality without reaching statistical significance.…”