Analysis of post-mortem brain samples from multiple sclerosis (MS) patients and healthy individuals (without neurologic disease) showed that while signs of Epstein-Barr virus (EBV) infection are present in both groups of brains, EBV-positive immune cells were more prevalent and densely populated in the MS brain.
The study reporting those findings, “Molecular signature of Epstein-Barr virus infection in MS brain lesions,” was published in the journal Neurology: Neuroimmunology & Neuroinflammation, the official journal of the American Academy of Neurology.
EBV infection is estimated to affect about 95% of adults worldwide, and previous studies have suggested a potential causal link between EBV infection and the risk for MS. These studies reported that MS patients had higher levels of antibodies against EBV than non-MS individuals, but follow-up studies have failed to find the same results.
Now, researchers analyzed autopsied brain samples from a MS brain tissue bank and from healthy, non-MS samples (controls).
They detected signs for the presence of EBV in 93% of MS brain samples, but also in the controls, although to a less extent (78%).
EBV infects immune B-cells, and the results showed that 85% of MS brain samples contained a higher percentage of B-cells positive for EBV-encoded RNA. In contrast, almost none of these cells were found in brain samples from controls.
“The Neurology publication extends the growing body of evidence linking EBV infection and MS using a well-characterized MS brain tissue bank,” Chris Haqq, MD, PhD, said in a press release. Haqq is executive vice president of research and development and chief scientific officer of Atara Biotherapeutics.
“We observed that EBV is present in both MS and control brains, with EBV-infected B-cells and plasma cells more prevalent and localized to MS brain lesions,” Haqq said.
Within immune B-cells, EBV switches between latent and lytic forms. The latent form is a way for the virus to evade the host’s immune system, whereas the lytic form corresponds to a state in which the virus replicates more actively. EBV infection was detectable in both MS and non-MS brains. although latent virus was more prevalent in MS brains, and lytic virus was restricted to chronic MS lesions.
“Taken together, our results that are derived from a well-characterized MS brain tissue bank support previous studies demonstrating the presence of EBV in the MS brain,” the team concluded.
“These findings advance the understanding of EBV’s potential role in MS pathogenesis and provide support for targeting EBV-infected immune cells associated with chronic MS lesions as a potential treatment for this severe autoimmune disorder,” Haqq said.
Atara is developing two therapies, ATA188 and ATA190, to eliminate EBV-infected B-cells in the central nervous system that can induce autoimmune responses and potentially contribute to MS development. Early results suggest these therapies can induce clinical improvements in MS symptoms.
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