January 17, 2022

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Epstein-Barr virus can increase the risk of multiple sclerosis by nearly 32 times

Epstein-Barr virus can increase the risk of multiple sclerosis by nearly 32 times

Epstein-Barr virus can increase the risk of multiple sclerosis by nearly 32 times. 

“Science” : Data analysis of more than 10 million people shows that EB virus infection can increase the risk of multiple sclerosis by nearly 32 times.

Our human body is often compared to a “highly precise instrument”.

The instrument may malfunction due to program settings or external forces.

The same is true for the human body.

Patients with autoimmune diseases are such a group of people who are highly troubled by this.

Multiple sclerosis is a type of autoimmune disease. Because the immune system abnormally attacks the myelin sheath of the brain and spinal cord nerves, causing inflammation and attracting macrophages to “eat up” the myelin sheath, nerve fibers lose this protective layer. “Naked”.

As a result, patients with multiple sclerosis often experience a variety of neurological symptoms, such as vision and sensory loss, muscle weakness, balance disorders, and movement disorders, which can lead to disability and death.

To make matters worse, at present, we do not know its pathogenesis, and the drugs used are only to relieve symptoms and reduce recurrence.

On January 13, Researchers from Harvard T.H. Chan School of Public Health published a study [1].

They analyzed the data of more than 10 million people and found that EB virus may be multiple sclerosis (MS) A predisposing factor, the risk of MS increases nearly 32-fold in people infected with EBV!

Epstein-Barr virus can increase the risk of multiple sclerosis by nearly 32 times

They believe this is an important finding in understanding MS, as it may be possible to prevent some cases of MS by preventing Epstein-Barr virus infection.

In fact, the view that “viral infection is the cause of MS” has been proposed by some researchers before [2], and EB virus is the primary “candidate” [3].

Pathological studies have shown that some MS patients have demyelinating lesions.

Epstein-Barr virus has indeed been detected in [4-6], but the relationship between Epstein-Barr virus infection and MS is uncertain.

To do this, the researchers examined a cohort of active-duty U.S. military personnel, a multiracial cohort of more than 10 million, from 1993-2013.

Due to the need for regular HIV testing, they receive blood tests at the time of enlistment and every two years after enlistment, and the remainder of the tests are stored in a serum bank of more than 62 million.

A total of 955 cases of MS were diagnosed in this cohort, and each case was matched to two other randomly selected non-MS patients with the same age, sex, race/ethnicity, military service, and date of blood sample collection as controls.

There were 35 and 107 cases in the case group and the control group, respectively, who were not infected with EB virus at the first blood test .

All but 1 of the 35 MS cases were infected with EB virus during the follow-up period, and all of them were infected with EB virus before the onset of MS. Seroconversion occurs (antibodies to Epstein-Barr virus can be detected) .

The median time from the first detection of an EBV-positive sample to the onset of MS was 5 years, while the estimated median time from EBV seroconversion (defined as the midpoint between the last blood sample negative and the first seropositivity) time) to the onset of MS was 7.5 years.

Among all people infected with EBV during the follow-up period, 97% of those who developed MS seroconverted and only 57% of those who did not develop MS , a contrasting difference in seroconversion rates consistent with a previous report [7].

Based on this calculation, EBV seroconverters had a 31.4-fold increased risk of developing MS compared to those who were consistently EBV seronegative (p < 0.001).

Epstein-Barr virus can increase the risk of multiple sclerosis by nearly 32 times

Proportion of EBV seropositive samples from MS patients (green) and non-patients (blue)

In contrast, cytomegalovirus, which is a herpes virus like Epstein-Barr virus, is also transmitted through saliva, and has similar age of infection and differences in socioeconomic and racial/ethnic infection rates in the United States, was not found to be associated with an increased risk of MS.

The high correlation, even the cytomegalovirus-positive group had a slightly lower risk of MS than the negative group.

Using an ultrasensitive single-molecule assay, the researchers found that serum neurofilament light chain (sNfL) levels were similar in the MS and control groups before EBV seroconversion, but increased in the MS group after EBV seroconversion , sNfL is a typical neurodegenerative biomarker in MS patients, although not MS-specific, but with high sensitivity.

This means that, in people who later develop MS, there is no evidence of neurodegeneration prior to EBV seroconversion, suggesting that EBV infection predates not only the onset of MS but also the first detectable biomarker changes .

The researchers used VirScan, a detection method based on T7 phage display immunoprecipitation and sequencing technology that covers about 200 known human pathogenic viruses, to comprehensively detect antiviral antibodies in blood samples.

In the case group and the control group, except for EB virus, there was no difference in other antibody responses, and the difference in EB virus antibody before and after the onset of the case group was also very significant.

This supports the specificity of the association between Epstein-Barr virus and MS and rules out potential effects of other viruses.

Epstein-Barr virus can increase the risk of multiple sclerosis by nearly 32 times

overall process of research

To move this result from correlation to causation, it is necessary to exclude the explanation of systematic differences between EBV seroconversion-positive and negative groups, which can be divided into two categories: the influence of known or unknown confounders and reverse causality relation.

Regarding confounders, the researchers believe that, given the strong association they found between EBV and MS, this can be ruled out because to explain the 31.4-fold increased risk, confounders would have to confer an increased risk for both EBV and MS It takes more than 60 times to get such a result, and none of the currently known or suspected confounding factors have such a strong impact, and it is not realistic that an unknown factor with such a strong impact has not yet been discovered.

Regarding reverse causality, the researchers said that if it is due to immune dysregulation in the preclinical stage where MS does not develop, it may increase EB virus susceptibility, which leads to reverse causality, but the above antiviral antibody detection experiments have been showed no antibody differences other than Epstein-Barr virus, implying that it is unlikely that immune dysregulation increases virus susceptibility.

This is consistent with previous reports of no difference in the frequency of infections occurring in MS patients 5 years before MS onset or in untreated MS [8,9].

Therefore, the researchers believe that, based on these results, Epstein-Barr virus infection, which can be detected by antibodies, is the cause, not the result, of MS.

They suggest that the longer delay between EBV infection and the onset of MS may be partly due to the fact that MS symptoms are not detected or appreciated in the early stages, and partly due to the fact that EBV infection can lie dormant in B cells, reactivate with repeated stimulation, and eventually lead to the onset of MS.

There is currently no effective way to prevent or treat EB virus infection, but they believe that in the future, EB virus vaccines or targeted antiviral drugs can be used to prevent or treat MS.


[1] https://www.science.org/doi/10.1126/science.abj8222

[2] Ascherio A, Munger K L. Environmental risk factors for multiple sclerosis. Part I: the role of infection[J]. Annals of neurology, 2007, 61(4): 288-299.

[3] Thorley-Lawson D A. Epstein-Barr virus: exploiting the immune system[J]. Nature Reviews Immunology, 2001, 1(1): 75-82.

[4] Serafini B, Rosicarelli B, Franciotta D, et al. Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain[J]. Journal of Experimental Medicine, 2007, 204(12): 2899-2912.

[5] Moreno MA, Or-Geva N, Aftab BT, et al. Molecular signature of Epstein-Barr virus infection in MS brain lesions[J]. Neurology-Neuroimmunology Neuroinflammation, 2018, 5(4).

[6] Hassani A, Corboy JR, Al-Salam S, et al. Epstein-Barr virus is present in the brain of most cases of multiple sclerosis and may engage more than just B cells[J]. PloS one, 2018, 13 (2): e0192109.

[7] Crawford DH, Macsween KF, Higgins CD, et al. A cohort study among university students: identification of risk factors for Epstein-Barr virus seroconversion and infectious mononucleosis[J]. Clinical infectious diseases, 2006, 43(3): 276-282.

[8] Wijnands JMA, Zhu F, Kingwell E, et al. Prodrome in relapsing‐remitting and primary progressive multiple sclerosis[J]. European journal of neurology, 2019, 26(7): 1032-1036.

[9] Sibley WA, Bamford, CR, Clark K. Clinical viral infections and multiple sclerosis[J]. Lancet, 1985: 1313-1315.

Epstein-Barr virus can increase the risk of multiple sclerosis by nearly 32 times

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