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AHSCT awakens EBV in MS, yet relapse remains at bay

25 October 2023

  • AHSCT reactivates the latent EBV in a study of people with MS.
  • EBV reactivation after AHSCT did not lead to MS relapses.
  • AHSCT led to a stronger defence against EBV, providing valuable information about AHSCT and future treatments for MS that target EBV.

The intricate interplay of MS, EBV, and AHSCT

Researchers from St Vincent’s Hospital, Sydney, and The Garvan Institute of Medical Research have been exploring the relationship between a powerful treatment known as autologous hematopoietic stem cell transplantation (AHSCT) for multiple sclerosis (MS) and a common virus called Epstein-Barr virus (EBV), along with the body’s immunity to this virus.

What is AHSCT? 

AHSCT is an intensive therapy for MS that involves using chemotherapy to rest the immune system. After depleting the immune system, the person’s own previously collected stem cells are put back into the bloodstream.  

This process helps to ‘grow’ a new immune system that is designed to be more ‘tolerant’ or less reactive to the brain and spinal cord, which is beneficial for people with MS.

Why study EBV after AHSCT?

This research focused on EBV, a virus that can hide in specialised immune cells known as memory B cells.

There is now strong evidence linking EBV to MS risk, but it is unclear how it may affect ongoing disease or MS relapses.

Usually, our immune system keeps these hidden (latent) viruses in check, but after AHSCT treatment, the immune system is weakened and potentially allows hidden viruses like EBV to reactivate. By examining how EBV behaves after AHSCT, we can learn more about its role in MS and how it affects the disease.

What did the researchers do?

MS Australia-funded researcher, Dr Jennifer Massey and her team followed 13 people with MS, carefully monitoring any clinical relapses and changes in disability.

To better understand the effects of AHSCT, the researchers collected blood samples from the participants before the procedure and then at 6, 12, and 24 months after. They closely observed the behaviour of the EBV virus after AHSCT.

They used advanced tests to assess the strength and extent of the body’s immune response against various parts of the EBV virus. Some of these components of the virus are only made when the virus is active. This information helps the researchers understand how EBV behaves during and after AHSCT.

What did the researchers find?

The study, published in The Journal of Clinical Immunology, uncovered several key findings. Firstly, when they looked at the stem cell treatments used in AHSCT, they found that these preparations contained memory B cells infected with EBV. This means that during the stem cell transplant, after chemotherapy, EBV was introduced back into the participant’s bloodstream.

The researchers found that none of the participants experienced a worsening of disability, eight experienced significant improvements in disability, and only two experienced an MS relapse after AHSCT.

After AHSCT, the levels of EBV increased in most of the participants, specifically 10 out of the 13 people studied. However, this reactivation of EBV in B cells after AHSCT didn’t lead to relapses in MS.

The researchers also discovered that the immune responses against both active and inactive (latent) parts of EBV increased and became more diverse from 6 to 24 months after AHSCT. In simpler terms, the immune system’s ability to fight different aspects of the virus became stronger and more varied during this time.

What does this mean for people with MS?

This research raises important questions about the role of EBV in the development of MS.  Interestingly, AHSCT does alter the way the immune system deals with EBV, but it didn’t result in MS relapses among the people they studied. What’s even more remarkable is that the positive impact of AHSCT endures for years after the treatment.

In this study, most people had increased EBV levels in their blood during the two years following treatment. However, this increase didn’t seem to lead to any problems. This may be because a more robust defence against EBV develops after AHSCT, but further research is needed to understand this.

The information from this study is invaluable for understanding how EBV, MS, and AHSCT are interconnected. It also carries significant implications for developing therapies that target EBV-specific immune cells for MS treatment.

While the study had a limited number of participants, it gives us a better understanding of the complex relationship between MS, EBV, and AHSCT, and may offer insights for the development of future MS treatments.

For more information on AHSCT, see here.

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AHSCT awakens EBV in MS, yet relapse remains at bay