Mystery solved? Epstein–Barr antibodies can trigger MS
Scientists have unearthed the pathological link between Epstein–Barr infection and MS, with new evidence confirming viral antibodies can also mistakenly attack the CNS and trigger the disease.
The findings not only explain why some people are prone to MS but could also lead to new therapies to halt disease progression rather than just reducing the risk of relapse, the researchers say.
“Our study provides an important piece in the puzzle,” said study author Dr Olivia Thomas (PhD), from the Karolinska Institutet in Sweden.
It follows a landmark 20-year study of more than 10 million US military personnel, published in Science in January last year.
The Harvard University–led researchers reported that the risk of MS increased 32-fold after infection with Epstein–Barr virus (EBV) but not other viruses, such as CMV.
“[Our] findings strongly suggest that the occurrence of EBV infection … is a cause and not a consequence of MS,” they concluded.
Although finding a mechanistic pathway was not their focus, theories suggested that molecular mimicry — EBV antibodies inadvertently targeting CNS proteins with similar amino acid sequences — played a significant role in MS pathogenesis.
The Swedish researchers demonstrated that this theory held true in up to a quarter of MS cases.
They analysed blood samples from 713 patients with MS and 722 healthy controls to determine whether the EBV antibody — EBV nuclear antigen 1 (EBNA1) — also reacted with the CNS protein alpha-crystallin B (CRYAB), which is implicated in MS development.
They confirmed that antibody cross-reactivity between EBNA1 and CRYAB was present in about 23% of those with MS compared with 7% in the control group.
“The anti-CRYAB reactivity was similar in persons with relapsing-remitting, secondary progressive and primary progressive MS and was not correlated with age, disease duration or sex,” the authors wrote in Science Advances.
In a separate animal model, they also identified increased T-cell cross-reactivity, which further demonstrated the role of EBV adaptive immune responses in MS development.
This was subsequently confirmed in a subset of patients with MS who were treated with the monoclonal antibody natalizumab.
“We are now expanding our research to investigate how T-cells fight EBV infection and how these immune cells may damage the nervous system in MS and contribute to disease progression,” said study author Dr Mattias Bronge.
Read more: More evidence Epstein–Barr triggers MS
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