Dataset Information

No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome.

ABSTRACT: Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) are associated with a variety of conditions including rash, fever, and encephalitis and may play a role in several neurological diseases. Here luciferase immunoprecipitation systems (LIPS) was used to develop HHV-6 serologic diagnostic tests using antigens encoded by the U11 gene from HHV-6A (p100) and HHV-6B (p101). Analysis of the antibody responses against Renilla luciferase fusions with different HHV-6B p101 fragments identified an antigenic fragment (amino acids 389 to 858) that demonstrated ~86% seropositivity in serum samples from healthy US blood donors. Additional experiments detected a HHV-6A antigenic fragment (amino acids 751-870) that showed ~48% antibody seropositivity in samples from Mali, Africa, a known HHV-6A endemic region. In contrast to the high levels of HHV-6A immunoreactivity seen in the African samples, testing of US blood donors with the HHV-6A p100 antigenic fragment revealed little immunoreactivity. To potentially explore the role of HHV-6 infection in human disease, a blinded cohort of controls (n=59) and chronic fatigue syndrome (CFS) patients (n=72) from the US was examined for serum antibodies. While only a few of the controls and CFS patients showed high level immunoreactivity with HHV-6A, a majority of both the controls and CFS patients showed significant immunoreactivity with HHV-6B. However, no statistically significant differences in antibody levels or frequency of HHV-6A or HHV-6B infection were detected between the controls and CFS patients. These findings highlight the utility of LIPS for exploring the seroepidemiology of HHV-6A and HHV-6B infection, but suggest that these viruses are unlikely to play a role in the pathogenesis of CFS.

SUBMITTER: Burbelo PD

PROVIDER: S-EPMC3493030 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome.

Burbelo Peter D PD Bayat Ahmad A Wagner Jason J Nutman Thomas B TB Baraniuk James N JN Iadarola Michael J MJ

American journal of translational research 20121010 4

Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) are associated with a variety of conditions including rash, fever, and encephalitis and may play a role in several neurological diseases. Here luciferase immunoprecipitation systems (LIPS) was used to develop HHV-6 serologic diagnostic tests using antigens encoded by the U11 gene from HHV-6A (p100) and HHV-6B (p101). Analysis of the antibody responses against Renilla luciferase fusions with different HHV-6B p101 fragments identified ...[more]

PMID: 23145212

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Project description:Prospective cohort studies following individuals from acute infections have documented a prevalent post-infective fatigue state meeting diagnostic criteria for chronic fatigue syndrome (CFS) - that is, a post-infective fatigue syndrome (PIFS). The Dubbo Infection Outcomes Study (DIOS) was a prospective cohort following individuals from acute infection with Epstein-Barr virus (EBV), Ross River virus (RRV), or Q fever through to assessment of caseness for CFS designated by physician and psychiatrist assessments at 6 months. Previous studies in DIOS have revealed that functional genetic polymorphisms in both immunological (pro- and anti-inflammatory cytokines) and neurological (the purinergic receptor, P2X7) genes are associated with both the severity of the acute infection and subsequent prolonged illness. Principal components analysis was applied to self-report data from DIOS to describe the severity and course of both the overall illness and concurrent mood disturbance. Associations between demographics and acute infection characteristics, with prolonged illness course as well as the PIFS outcome were examined using multivariable statistics. Genetic haplotype-driven functional variations in the neuropeptide Y (NPY) gene previously shown to be associated with brain responses to stress, and to trait anxiety were also examined as predictors. The sample included 484 subjects (51% female, median age 32, IQR 19-44), of whom 90 (19%) met diagnostic criteria for CFS at 6 months. Participants with greater overall illness severity and concurrent mood disturbance in the acute illness had a more prolonged illness severity (HR = 0.39, 95% CI: 0.34-0.46, p < 0.001) and mood disturbance (HR = 0.36, 95% CI: 0.30-0.42, p < 0.001), respectively. Baseline illness severity and RRV infection were associated with delayed recovery. Female gender and mood disturbance in the acute illness were associated with prolonged mood disturbance. Logistic regression showed that the odds of an individual being diagnosed with PIFS increased with greater baseline illness severity (OR = 2.24, 95% CI: 1.71-2.94, p < 0.001). There was no association between the NPY haplotypes with overall illness severity or mood disturbance either during the acute illness phase or with prolonged illness (p > 0.05). Severe acute infective illnesses predicted prolonged illness, prolonged mood disturbance and PIFS. These factors may facilitate early intervention to manage both PIFS and mood disturbances.

Project description:BackgroundExposure to Epstein-Barr virus (EBV) infection has been hypothesized to be an important risk factor for multiple rheumatic diseases, but the serological evidence so far for its role in Sjögren's syndrome (SjS) is not clearly established yet. This study aimed to assess the seroepidemiological associations of antibodies to EBV with SjS.MethodsA seroepidemiological study containing 119 patients with SjS and 65 healthy controls was first performed, in which the associations of SjS with four commonly studied EBV antibodies including IgM-anti-viral capsid antigen (anti-VCA) antibody, IgG-anti-VCA antibody, IgG-anti-early antigen (anti-EA) antibody, and IgG-anti-EBV nuclear antigen 1 (anti-EBNA1) antibody were evaluated. A systematic review and meta-analysis of eligible seroepidemiological studies was also carried out, and data syntheses were performed using random-effect meta-analysis.ResultsIn the case-control study, the patients with SjS had both a significantly higher prevalence of IgG-anti-EA antibody positivity (31.9% vs. 3.1%, P < 0.001) and high titers of IgG-anti-EA antibody (P < 0.001) than healthy controls. The titer of IgG-anti-VCA antibody was significantly increased in the patients with SjS compared with healthy controls (P < 0.001). IgG-anti-EA antibody seropositive patients with SjS had lower levels of both C3 (P = 0.002) and C4 (P = 0.02), and the titer of IgG-anti-EA antibody was inversely related to the levels of both C3 (r = -0.31, P < 0.001) and C4 (r = -0.20, P = 0.03). A total of 14 eligible studies on the serological associations between EBV infection and SjS were finally included into the meta-analysis, which suggested obvious associations of SjS with IgM-anti-VCA antibody [Odds ratio (OR) = 5.77, 95%CI 1.73-19.25, P = 0.004] and IgG-anti-EA antibody (OR = 9.97, 95%CI 4.58-21.67, P < 0.00001).ConclusionsThe findings from this study provide strong serological evidence for the association between EBV infection and SjS. SjS has obvious associations with IgM-anti-VCA antibody and IgG-anti-EA antibody. IgG-anti-EA antibody is linked to low levels of C3 and C4 in the patients with SjS, the significance of which needs to be addressed in further studies.

Dataset Information

No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome.

Publications

No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome.

Similar Datasets

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