Summary: Researchers have discovered a new link between the Epstein-Barr virus (EBV) and the development of multiple sclerosis (MS).
Their research shows that antibodies originally intended to fight EBV can mistakenly target proteins in the brain and spinal cord, leading to MS symptoms. This antibody misdirection was found in 23% of MS patients studied.
The findings highlight the need for personalized therapies to combat MS.
- The Epstein-Barr virus (EBV) infects many people early in life and remains dormant in the body, but is associated with the development of multiple sclerosis.
- In 23 percent of MS patients, antibodies against EBV mistakenly target the same protein in the brain and spinal cord, which can cause MS symptoms.
- The high variability of antibody responses among MS patients highlights the need for personalized therapies.
Source: Karolinska Institute
Researchers at the Karolinska Institute in Sweden have found more evidence of how the Epstein-Barr virus can trigger multiple sclerosis or cause disease progression.
A study published in Advances in science It shows that some individuals have antibodies to the virus that mistakenly attack the protein in the brain and spinal cord.
The Epstein-Barr virus (EBV) infects many people early in life and then remains in the body, usually without causing symptoms.
The link between EBV and the neurological disease multiple sclerosis (MS) was discovered many years ago and has puzzled researchers ever since.
Additional evidence including two papers published in Science And Nature In the past year, it has been suggested that EBV infection precedes MS and that there may be antibodies that protect against the virus. However, the molecular mechanisms differ between patients and seem to be poorly understood.
“MS is a very complex disease, but our study provides an important piece of the puzzle and may explain why some people develop the disease,” shared Olivia Thomas, postdoctoral researcher at the Department of Clinical Neuroscience, Karolinska Institutet and first author. Paper.
“We found that some of the Epstein-Barr virus antibodies that normally fight the infection can mistakenly target the brain and spinal cord and cause damage.”
Antibodies of the wrong direction
The researchers analyzed blood samples from more than 700 patients with MS and 700 healthy individuals. They found that antibodies that bind to a specific protein in Epstein-Barr virus EBNA1 can also bind to a similar protein called CRYAB in the brain and spinal cord. .
These misdirected, reactive antibodies can damage the nervous system and cause severe symptoms in MS patients, including problems with balance, mobility, and fatigue. Antibodies were found in 23 percent of MS patients and 7 percent of control individuals.
“This shows that these antibodies are not necessary for the development of the disease, but may be involved in the disease in up to a quarter of MS patients,” said Olivia Thomas.
“This also shows the great variability between patients, which highlights the need for personalized treatments. Current treatments are effective in reducing relapses in MS, but unfortunately none can prevent the progression of the disease.”
T cells may also be involved.
The researchers discovered that a similar reactivity may exist in the immune system’s T cells.
“We are now expanding our study to investigate how T cells fight EBV infection and how these immune cells damage the nervous system in multiple sclerosis and contribute to disease progression,” says Matthias Bronz, co-researcher at the Department of Clinical Neuroscience at Karolinska Institutet. And shared the first author of the paper.
Financial support The research was funded by the Swedish Innovation Agency Vinnova, the Swedish Research Council, the Swedish Brain Foundation, Karolinska Institutet, MS Forskningsfonden, Neuro and Region Stockholm.
Co-author Hans Gronlund is an inventor on a current patent filed by NEOGAP Therapeutics AB and is the founder and co-owner of this company. Birce Akpinar, Ola B. Nilsson, Erik Holmgren and Guro Gafvelin hold positions at NEOGAP Therapeutics AB.
Roland Martin is a co-founder, co-owner and employee of Celerius from the University of Zurich, and holds patents and patents for several patents.
Roland Martin and Thomas Olsen have received financial support and fees from several companies. See the scientific paper for a full list of authors’ conflicts of interest.
Fact box: Epstein-Barr virus
Herpes virus EBV is one of the most common viruses in humans. More than 90 percent of the world’s population is infected with EBV and carries the virus during their lifetime as a latent, often asymptomatic, infection.
Most people are infected in childhood with few or no symptoms, but in young adults, the virus often causes infectious mononucleosis, also known as glandular fever or the kissing disease.
So multiple sclerosis research news
Author: Press office
Source: Karolinska Institute
Contact: Press Office – Karolinska Institute
Image: Image credited to Neuroscience News.
Preliminary study: Open Access.
“Cross-reactive EBNA1 antibodies target alpha-crystallin B and are associated with multiple sclerosis.” by Olivia Thomas et al Advances in science
Cross-reactive EBNA1 antibodies target alpha-crystallin B and are associated with multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, which is caused by Epstein-Barr virus (EBV) infection.
Due to the homology between Epstein-Barr nuclear antigen 1 (EBNA1) and alpha-crystallin B (CRYAB), we examined antibody responses to EBNA1 and CRYAB peptide libraries in 713 people with MS (pwMS) and 722 matched controls (con).
Antibody responses to CRYAB amino acids 7 to 16 were associated with MS (OR = 2.0), and high EBNA1 responses combined with CRYAB positivity increased disease risk (OR = 9.0). Blocking experiments showed antibody reactivity between homologous EBNA1 and CRYAB epitopes.
Evidence of T cell cross-reactivity was found in mice between EBNA1 and CRYAB, and CRYAB and EBNA1 increased CD4.+ T cell responses detected in pwMS treated with natalizumab.
This study provides evidence of antibody cross-reactivity between EBNA1 and CRYAB and suggests a similar immune response in T cells, further demonstrating the role of EBV adaptive immune responses in the development of MS.