History of EBV and MS

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History of EBV and MS

Postby dignan » Wed Apr 26, 2006 12:48 pm

The association between Epstein-Barr Virus and MS has been studied for a long time and continues to be a topic of significant interest. I was curious to see just how long this has been going on. References to EBV and MS in Pubmed start in the mid-1970s.

Anyhow, just for fun (ok, maybe not fun...) here are a few examples of Pubmed article abstracts that are all AT LEAST 20 years old:

Arch Neurol. 1980 Feb;37(2):94-6.
Epstein-Barr virus antibodies in multiple sclerosis.
Sumaya CV, Myers LW, Ellison GW.

Serum antibody titers to Epstein-Barr virus (EBV), an agent that persists in a latent form after the initial infection, were determined in 157 patients with multiple sclerosis and in 81 control subjects. Two patients (1.3%) and five control subjects (6.2%) lacked antibodies to EBV. In the subjects with antibodies, the prevalence of high titers (greater than or equal to 1:160) was significantly greater in patients, 69 (44.5%), than in control subjects, 22 (28.9%). The geometric mean titer of antibodies to EBV was significantly higher in patients, 107.0, than in control subjects, 77.1. There was no association between antibody titers and duration or activity of the disease. These findings further support the contention that patients with multiple sclerosis have a general aberration of the immunological system.

Arch Neurol. 1983 Jul;40(7):406-8.
Epstein-Barr virus infection and antibody synthesis in patients with multiple sclerosis.
Bray PF, Bloomer LC, Salmon VC, Bagley MH, Larsen PD.

We studied infectious and immune mechanisms in demyelinating disease. The clinical diagnosis in this study of 313 consecutive cases of multiple sclerosis (MS) was based on the clinical conclusions of two or more neurologists and definite abnormalities in CSF IgG. Measurement of antibodies to six microbial agents was compared in 313 patients with MS and 406 controls in the same age range. Using a standardized immunofluorescent antibody (IFA) technique, we found a significantly higher prevalence of Epstein-Barr virus (EBV) infection and a higher level of serum viral capsid antigen IgG antibody titer in the MS population than in the controls. The MS population had a lower cytomegalovirus (CMV) infection rate and lower CMV complement fixing antibody production than controls. Except for the higher measles infection rate and antibody titer in patients with MS, data on the other viruses did not differ from controls.

Neurology. 1985 Mar;35(3):435-8.
Epstein-Barr nuclear antigen and viral capsid antigen antibody titers in multiple sclerosis.
Larsen PD, Bloomer LC, Bray PF.

To characterize the antibody response to the Epstein-Barr virus (EBV) in MS, we studied serum anti-EBV nuclear antigen (anti-EBNA) and anti-EBV capsid antigen (anti-EBVCA) titers. Both titers were assayed in 93 age- and sex-matched pairs of MS patients and controls. Anti-EBVCA titers were measured by indirect immunofluorescence and anti-EBNA titers by anticomplement immunofluorescence. The seropositivity rate of both anti-EBVCA and anti-EBNA in MS patients was 100%, compared with 84% in controls (p less than 0.0001). Both anti-EBVCA and anti-EBNA titers were significantly higher in MS patients than in controls (p less than 0.0001). The data suggest that EBV has a significant seroepidemiologic association with MS, but they do not define what role EBV antibodies play in the pathogenesis of the disease.

Ann Neurol. 1985 Apr;17(4):371-7.
Increased prevalence and titer of Epstein-Barr virus antibodies in patients with multiple sclerosis.
Sumaya CV, Myers LW, Ellison GW, Ench Y.

The prevalence and titer of serum antibodies to several Epstein-Barr virus (EBV) antigens were compared among patients with multiple sclerosis, healthy siblings of multiple sclerosis patients, patients with other neurological diseases, and healthy non-blood-related subjects. Serum-cerebrospinal fluid (serum-CSF) pairs were available on a selected number of multiple sclerosis and control subjects. An increased antibody response to EBV antigens was noted rather consistently in the sera of the multiple sclerosis group in comparison with the control groups. A greater number of reduced ratios of serum:CSF IgG antibody to EBV-capsid antigen and antibody to EBV-early antigen components than to adenovirus, a reference or control virus, were found in the multiple sclerosis group. Reduced ratios of these EBV antibodies were detected more frequently or showed a trend in this direction in multiple sclerosis patients compared with the group with other neurological diseases. Our findings extend the results of an earlier report and strengthen the association between EBV and multiple sclerosis.

Neurology. 1985 Aug;35( 8 ):1176-80.
Viral antibodies in twins with multiple sclerosis.
Woyciechowska JL, Dambrozia J, Leinikki P, Shekarchi C, Wallen W, Sever J, McFarland H, McFarlin D.

Viral antibodies to measles, rubella, corona, vaccinia, and mumps viruses in serum and CSF (and to Epstein-Barr virus in serum only) were studied in 24 twin pairs, both discordant and concordant for clinical MS. In pairs, CSF antibody titers for rubella in MS monozygotic and dizygotic twins and for vaccinia in dizygotic twins were higher than for unaffected twins. Increased CSF titers among MS twins existed for measles, rubella, and vaccinia when pairing was ignored. Among MS twins, serum rubella and measles and CSF measles antibody titers, and CSF:serum ratios for measles virus, were higher in those who were DW2 positive.
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Postby Arron » Wed Apr 26, 2006 1:23 pm

interesting research... thanks Dignan.
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Yes, interesting research!

Postby lyndacarol » Wed Apr 26, 2006 1:51 pm

I just wiped out two paragraphs--I had become too emotional. I will just say "thank you" for all your research and contributions to this site.

I get so impatient for answers!
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Re: History of EBV and MS

Postby NHE » Thu Apr 27, 2006 2:49 am

Thanks for the review on EBV and MS. This paper's a little newer but it may provide a mechanism for why EBV may be important in MS. It's food for thought none the less.

    EBV-Induced Expression and HLA-DR-Restricted Presentation by Human B Cells of aB-Crystallin, a Candidate Autoantigen in Multiple Sclerosis
    The Journal of Immunology, 1999, 162:129–135.

    The development of multiple sclerosis is most likely influenced by autoimmune responses to central nervous system myelin proteins as well as by infections with common viruses such as EBV and human herpesvirus-6. However, much remains to be established on how these factors interact. In this study, we show that upon EBV infection, human B cells start to express aB-crystallin, a small stress protein that was identified previously as an immunodominant Ag of CNS myelin in multiple sclerosis patients. EBV-induced expression of aB-crystallin in B cells leads to HLA-DR-restricted presentation of the protein and to activation of proinflammatory aB-crystallin-specific Th cells. While aB-crystallin is present in EBV-infected human B cells, the protein is absent from human lymphoid tissues under normal conditions. This is in sharp contrast to other stress proteins such as heat-shock protein (hsp)27 and hsp60 that are ubiquitously expressed in these tissues. In addition, the absence of aB-crystallin from lymphoid tissues in humans is unique as compared with other mammals. All other species examined, including rodents, sheep, and primates, showed constitutive expression of aB-crystallin in secondary lymphoid tissues and sometimes even in the thymus. Since constitutive lymphoid expression most likely results in immunologic tolerance, such a state of tolerance to aB-crystallin can be expected for all of these species, but not for humans. When taken together, our data provide evidence for a novel mechanism by which common viral infections can trigger myelin-directed autoimmunity in a way that is unique for humans.

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Postby bromley » Thu Apr 27, 2006 4:14 am


Thanks for this. The B cell issue is interesting and might explain why Rituximab (Rituxin), which targets B cells, has shown promise.

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