Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis

Simpson, Steve; Taylor, Bruce; Dwyer, Dominic E.; Taylor, Janette; Blizzard, Leigh; Ponsonby, Anne–Louise; Pittas, Fotini; Dwyer, Terence; Mei, Ingrid van der

doi:10.1177/1352458511428081

Cited by 55 publications

(57 citation statements)

References 37 publications

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“…Peripheral administration of lipopolysaccharide increases inflammatory and oxidative stress in brain, and glial activation in the hippocampus, to a greater extent in aged, compared with young, rats [11]. Consistently, age is associated with increased vulnerability to infections, while infections have been shown to accelerate progression of diseases such as Alzheimer's disease and multiple sclerosis [12], [13]. These findings support the notion that a communication network between the CNS and the periphery exists.…”

Section: Introductionsupporting

confidence: 66%

Modulation of Intestinal Microbiota by the Probiotic VSL#3 Resets Brain Gene Expression and Ameliorates the Age-Related Deficit in LTP

et al. 2014

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The intestinal microbiota is increasingly recognized as a complex signaling network that impacts on many systems beyond the enteric system modulating, among others, cognitive functions including learning, memory and decision-making processes. This has led to the concept of a microbiota-driven gut–brain axis, reflecting a bidirectional interaction between the central nervous system and the intestine. A deficit in synaptic plasticity is one of the many changes that occurs with age. Specifically, the archetypal model of plasticity, long-term potentiation (LTP), is reduced in hippocampus of middle-aged and aged rats. Because the intestinal microbiota might change with age, we have investigated whether the age-related deficit in LTP might be attenuated by changing the composition of intestinal microbiota with VSL#3, a probiotic mixture comprising 8 Gram-positive bacterial strains. Here, we report that treatment of aged rats with VSL#3 induced a robust change in the composition of intestinal microbiota with an increase in the abundance of Actinobacteria and Bacterioidetes, which was reduced in control-treated aged rats. VSL#3 administration modulated the expression of a large group of genes in brain tissue as assessed by whole gene expression, with evidence of a change in genes that impact on inflammatory and neuronal plasticity processes. The age-related deficit in LTP was attenuated in VSL#3-treated aged rats and this was accompanied by a modest decrease in markers of microglial activation and an increase in expression of BDNF and synapsin. The data support the notion that intestinal microbiota can be manipulated to positively impact on neuronal function.

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Section: Introductionsupporting

confidence: 66%

Modulation of Intestinal Microbiota by the Probiotic VSL#3 Resets Brain Gene Expression and Ameliorates the Age-Related Deficit in LTP

et al. 2014

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“…Furthermore, the increase of the anti-HHV-6A/B IgG and IgM titers predicts the upcoming clinical relapses. Recently, Simpson et al [30] published that HHV-6A/B infection or the immune response to HHV-6A/B antigens may have an effect on the risk of MS relapses, since the observed effect was directly related to anti-HHV-6A/B IgG titers and may indicate that either HHV-6A/B infection or factors associated with an altered humoral immune response to HHV-6A/B may have an effect on MS clinical course.…”

Section: Discussionmentioning

confidence: 99%

Anti-Human Herpesvirus 6A/B IgG Correlates with Relapses and Progression in Multiple Sclerosis

et al. 2014

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ObjectiveTo analyze the titers of the IgG and IgM antibodies against human herpesvirus 6A/B (HHV-6A/B) in multiple sclerosis (MS) patients treated with different disease modified therapies (DMTs) along two-years of follow-up.MethodsWe collected 2163 serum samples from 596 MS; for 301 MS patients a 2-years follow-up was performed. Serum samples of 337 healthy controls were also analyzed. Anti-HHV-6A/B IgG and IgM were analyzed by ELISA (Panbio).ResultsWe found that 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); the higher significance was found for natalizumab. Furthermore, we found that anti-HHV-6A/B IgG titers reached their highest value two weeks before the relapse (p = 0.0142), while the anti-HHV-6A/B IgM titers reached their highest value one month before the relapse (p = 0.0344).ConclusionThe measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical response to the different DMTs. The increase of the anti-HHV-6A/B IgG and IgM titers predicts the upcoming clinical relapses. However, further longitudinal studies are needed to validate these results.

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“…A 2012 study of a Tasmanian cohort found HHV-6 IgG titer to be a significant predictor of relapse risk [27]. This was echoed in a 2014 study of a Spanish MS cohort, which reported that a decrease in HHV-6 antibody titers correlated with fewer relapses and less disease progression [28].…”

Section: Traces Of Hhv-6 In the Periphery: Virus Detection And Virus-mentioning

confidence: 99%

Evidence linking HHV-6 with multiple sclerosis: an update

Leibovitch

Jacobson

2014

Current Opinion in Virology

109

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Following reports of elevated antiviral antibodies in MS patient sera and viral DNA detection in MS plaques nearly two decades ago, the neurovirology community has actively explored how herpesviruses such as HHV-6 might be involved in MS disease pathogenesis. Though findings across the field are nonuniform, an emerging consensus of viral correlates with disease course and evidence of HHV-6-specific immune responses in the CNS provide compelling evidence for a role, direct or indirect, of this virus in MS. Ultimately, the only way to demonstrate the involvement, or lack thereof, of HHV-6 or other herpesviruses in this disease is through a controlled clinical trial of an efficacious antiviral drug.

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Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis

Cited by 55 publications

References 37 publications

Modulation of Intestinal Microbiota by the Probiotic VSL#3 Resets Brain Gene Expression and Ameliorates the Age-Related Deficit in LTP

Modulation of Intestinal Microbiota by the Probiotic VSL#3 Resets Brain Gene Expression and Ameliorates the Age-Related Deficit in LTP

Anti-Human Herpesvirus 6A/B IgG Correlates with Relapses and Progression in Multiple Sclerosis

Evidence linking HHV-6 with multiple sclerosis: an update

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