Quantitative PCR for Epstein–Barr virus DNA and RNA in multiple sclerosis

Lindsey, J. W.; Hatfield, L. M.; Crawford, MP; Patel, Sankita J.

doi:10.1177/1352458508097920

Cited by 55 publications

(45 citation statements)

References 21 publications

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“…Furthermore, we do not detect EBV DNA either in the plasma or PBMC of MS patients or control subjects. This result, which contrasts with that of other investigators (10,13), could be due to methodological differences. Furthermore, because we tested one time point, which was not always the same as the cellular assay time point, we may have missed a transient increase in EBV viral load.…”

Section: Discussioncontrasting

confidence: 98%

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HLA-B7–Restricted EBV-Specific CD8+ T Cells Are Dysregulated in Multiple Sclerosis

Jilek

Schluep

Harari

et al. 2012

The Journal of Immunology

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It was hypothesized that the EBV-specific CD8+ T cell response may be dysregulated in multiple sclerosis (MS) patients, possibly leading to a suboptimal control of this virus. To examine the CD8+ T cell response in greater detail, we analyzed the HLA-A2–, HLA-B7–, and HLA-B8–restricted EBV- and CMV-specific CD8+ T cell responses in a high number of MS patients and control subjects using tetramers. Content in cytolytic granules, as well as cytotoxic activity, of EBV- and CMV-specific CD8+ T cells was assessed. We found that MS patients had a lower or a higher prevalence of HLA-A2 and HLA-B7, respectively. Using HLA class I tetramers in HLA-B7+ MS patients, there was a higher prevalence of MS patients with HLA-B*0702/EBVRPP-specific CD8+ T cells ex vivo. However, the magnitude of the HLA-B*0702/EBVRPP-specific and HLA-B*0702/CMVTPR-specific CD8+ T cell response (i.e., the percentage of tetramer+ CD8+ T cells in a study subject harboring CD8+ T cells specific for the given epitope) was lower in MS patients. No differences were found using other tetramers. After stimulation with the HLA-B*0702/EBVRPP peptide, the production of IL-2, perforin, and granzyme B and the cytotoxicity of HLA-B*0702/EBVRPP-specific CD8+ T cells were decreased. Altogether, our findings suggest that the HLA-B*0702–restricted viral (in particular the EBV one)-specific CD8+ T cell response is dysregulated in MS patients. This observation is particularly interesting knowing that the HLA-B7 allele is more frequently expressed in MS patients and considering that EBV is associated with MS.

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Section: Discussioncontrasting

confidence: 98%

“…However, whether an increased EBV viral load is present in MS patients remains controversial (10,13). There also may be an intrinsic dysregulation of EBV-specific CD8 + T cells in MS patients (14).…”

mentioning

confidence: 99%

HLA-B7–Restricted EBV-Specific CD8+ T Cells Are Dysregulated in Multiple Sclerosis

Jilek

Schluep

Harari

et al. 2012

The Journal of Immunology

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“…(iii) EBV viral load in serum or peripheral blood cells is only modestly increased in MS (Wagner et al 2004;Buljevac et al 2005;Lindsey et al 2009) (although children with MS shed EBV in saliva more frequently than healthy controls) (Yea et al 2013). (iv) Monoclonal antibodies (natalizumab) that block α4 integrin and thus prevent T-cell migration into the central nervous system (CNS) provide a very effective treatment against MS relapses (Polman et al 2006).…”

Section: Potential Mechanisms Relating Ebv To Msmentioning

confidence: 98%

EBV and Autoimmunity

Ascherio

Munger

2015

Current Topics in Microbiology and Immunology

104

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Although a role of EBV in autoimmunity is biologically plausible and evidence of altered immune responses to EBV is abundant in several autoimmune diseases, inference on causality requires the determination that disease risk is higher in individuals infected with EBV than in those uninfected and that in the latter it increases following EBV infection. This determination has so far been possible only for multiple sclerosis (MS) and, to some extent, for systemic lupus erythematosus (SLE), whereas evidence is either lacking or not supportive for other autoimmune conditions. In this chapter, we present the main epidemiological findings that justify the conclusion that EBV is a component cause of MS and SLE and possible mechanisms underlying these effects.

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“…While the viral load is extremely high in SLE, in MS it is similar to that seen in the healthy population [67]. This suggests that chronic reactivation of the EBV infection, as well as a detectable immune response to early EBV antigens occurs only in SLE, but not in MS. 3.…”

Section: Differences In the Relationship Between Ebv And The Disease mentioning

confidence: 83%

The role of the Epstein-Barr virus in the pathogenesis of some autoimmune disorders — Similarities and differences

Füst¹

2011

European Journal of Microbiology and Immunology

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After a brief summary on the properties of the Epstein-Barr virus (EBV), the course and latency stages of the infection, the characteristics of infectious mononucleosis (IM), and other disorders caused by this virus, as well as the course of the serological responses to EBV, the current paper focuses on the role of EBV in two autoimmune disorders: multiple sclerosis (MS), and systemic lupus erythematosus (SLE). Diverse evidence suggests that infection by EBV during late childhood or young adulthood may have a role in the pathogenesis of MS. These include the similarity between the geographical distribution of IM and MS, the high risk of contracting MS by individuals who have recovered from IM, the elevation of the titers of IgG antibodies against EBV nuclear antigens occurring years before the initial manifestations of MS, and the extremely rare occurrence of MS in individuals seronegative for EBV. However, the data on the mechanism underlying the relationship between EBV and MS are controversial. Moreover, many observations indicate that EBV contributes also to the pathomechanism of SLE. However, this contribution differs from the relationship between EBV and MS, as shown by the lack of any increase in the risk of SLE after IM. In SLE, EBV serology is quantitatively and qualitatively different from the normal response -that is, EBV viral load is higher and a strong cross-reaction can be detected between certain EBV antigens and autoantigens of pathological importance. These observations, along with the findings pointing to a possible role of EBV in rheumatoid arthritis and myasthenia gravis indicate that infection by EBV may be one of the environmental factors, which can facilitate the development of some autoimmune disorders in genetically susceptible individuals.

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Quantitative PCR for Epstein–Barr virus DNA and RNA in multiple sclerosis

Abstract: We conclude that the immune control of EBV infection is similar in MS and controls, and that reactivation of EBV may correlate with MS disease activity.

Cited by 55 publications

References 21 publications

HLA-B7–Restricted EBV-Specific CD8+ T Cells Are Dysregulated in Multiple Sclerosis

HLA-B7–Restricted EBV-Specific CD8+ T Cells Are Dysregulated in Multiple Sclerosis

EBV and Autoimmunity

The role of the Epstein-Barr virus in the pathogenesis of some autoimmune disorders — Similarities and differences

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