Scientists have shed light on how the Epstein-Barr virus (EBV) may contribute to the development of multiple sclerosis (MS), saying that certain antibodies produced to fight the infection might mistakenly target the brain and spinal cord, damaging the nervous system and contributing to balance and mobility problems associated with MS.
In addition, T cells, another part of the immune response that provides protection against infections, may also misfire and attack the nervous system, revealed the findings, published in Science Advances.
Prior evidence suggests that EBV infection is a prerequisite for MS, and scientists are just starting to uncover the mechanisms of how the virus may contribute to the development of the chronic inflammatory autoimmune disease of the central nervous system.
More than 90% of the population has had an EBV infection but only a small percentage develop MS, suggesting that other mechanisms – like genetic risk factors – are at play, reports Healthline.
“This new paper supports many other studies pointing to molecular mimicry as a major way that EBV infection contributes to the development of MS. Molecular mimicry is the idea that when the immune system targets EBV, it sometimes also ends up targeting human proteins that look like EBV proteins,” said Dr Michael Sy, an assistant professor with the Comprehensive Multiple Sclerosis Centre at University of California Irvine’s School of Medicine.
Protective antibodies
To better understand how EBV may trigger MS, researchers at Karolinska Institutet, Sweden, examined blood samples of 713 people with MS and 722 healthy individuals.
They found that the antibodies the body produces to fight the infection, known as EBNA1, can also bind to a protein, called CRYAB, in the brain spinal cord that protects the body from the harmful effects of inflammation.
When EBNA1 antibodies bind to the CRYAB proteins, as the study suggests, they could damage the nervous system, leading to MS problems relating to balance, mobility and fatigue.
The misdirected antibodies were detected in about 23% of people with MS and 7% of those who were healthy.
“In MS, the immune system is targeting molecules in the myelin sheath of the brain that look similar to molecules in EBV leading to damage to one’s own brain and spinal cord,” said Sy.
There also appeared to be cross-reactivity among T cells, which the body also stimulates to produce antibodies that fight infections.
“It seems highly likely that these misdirected cross-reactive B cells, antibodies, and T cells influence neuro-inflammation and contribute to the disease,” said Dr Tobias Lanz, an assistant professor of immunology and rheumatology at Stanford Medicine who has been trained in neurology.
Preventative MS care must be personalised
Most people – about 90% – are infected with EBV early in life. The virus stays in the body, dormant, typically without causing symptoms.
For years, scientists have known there’s a link between EBV and MS, with prior research suggesting the risk of MS increases 32-fold after an EBV infection.
A large study from 2022 found that nearly 100% of people with MS had previously been infected with EBV.
“Studies indicate that Epstein-Barr virus infection is necessary to develop MS. It appears to be almost impossible to get MS if you haven’t first been infected with EBV,” Sy said.
Not everyone who gets infected with EBV develops MS, and some otherwise healthy individuals may have these antibodies and never develop MS.
“Other genetic and environmental risk factors probably add additional risk to develop the disease,” said Lanz.
The variability in immune responses, and how they affect the nervous system, indicate that MS prevention needs to be highly personalised, said the researchers.
Eradication or suppression of EBV may also help prevent future cases of MS, said Sy.
And, according to Lanz, these findings may help scientists develop a vaccine against EBV that will help prevent MS.
“Currently, there is no EBV-specific therapy in MS. But understanding the exact mechanisms might reveal EBV molecules that could be targeted directly,” Lanz said.
Study details
Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis
Olivia Thomas, Mattias Bronge, Katarina Tengvall, Birce Akpinar, Ola Nilsson, Erik Holmgren, Tara Hessa, Guro Gafvelin, Mohsen Khademi and Ingrid Kockum
Published in Science Advances on 17 May 2023
Abstract
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which and Epstein-Barr virus (EBV) infection is a likely prerequisite. Due to the homology between Epstein-Barr nuclear antigen 1 (EBNA1) and alpha-crystallin B (CRYAB), we examined antibody reactivity to EBNA1 and CRYAB peptide libraries in 713 persons with MS (pwMS) and 722 matched controls (Con). Antibody response to CRYAB amino acids 7 to 16 was associated with MS (OR = 2.0), and combination of high EBNA1 responses with CRYAB positivity markedly increased disease risk (OR = 9.0). Blocking experiments revealed antibody cross-reactivity between the homologous EBNA1 and CRYAB epitopes. Evidence for T cell cross-reactivity was obtained in mice between EBNA1 and CRYAB, and increased CRYAB and EBNA1 CD4+ T cell responses were detected in natalizumab-treated pwMS. This study provides evidence for antibody cross-reactivity between EBNA1 and CRYAB and points to a similar cross-reactivity in T cells, further demonstrating the role of EBV adaptive immune responses in MS development.
See more from MedicalBrief archives:
Epstein-Barr virus may be leading cause of Multiple Sclerosis – Harvard cohort study
Misdiagnosis of multiple sclerosis found to be common
Viral illnesses linked to dementia, neurodegenerative diseases – US study