Does stem cell transplant deplete EBV reservoirs in MS?

Dr Jennifer Massey

St Vincent's Centre for Applied Medical Research, NSW

February 2023

specialisation: Immunology

focus area: Better treatments

funding type: Incubator

project type: ebv

Summary

This project investigated whether Epstein-Barr virus (EBV) may be the cause of MS through studying the effect of autologous haematopoietic stem cell transplant (AHSCT), a highly effective MS therapy, on an individual’s immune response to EBV. 

The project investigated whether EBV reactivates after AHSCT, as has been suggested by one prior study. The project determined whether people with MS who have undergone AHSCT who develop a new immune system capable of rapidly controlling EBV are more likely to have a sustained response to treatment. 

This research has direct implications on  

  1. Understanding of the role EBV plays in causing MS.
  2. Treatment of people with MS.  

This knowledge will help clinicians alter the way in which AHSCT is performed (e.g., with anti-viral or cellular therapies) to better control EBV if it is shown to be relevant to disease remission. 

Outcome

Dr Jennifer Massey and her team found that it was rare for EBV to infect the blood after more than three months following AHSCT. However, the T cells that fight EBV persist and remain detectable after AHSCT. These cells will multiply and become more varied in response to EBV in the body’s cells. These results suggest that while MS may be triggered by EBV, it is unlikely that EBV is the key driver of ongoing inflammation in MS. 

Dr Massey and her team found that AHSCT is linked with a therapeutic response that runs for years following the development of the new immune system. This occurs despite most people treated having increased EBV in their bodies in the two years following AHSCT. 

It may be paradoxical that AHSCT leads to improved outcomes even though EBV infections are reactivated. The study made an interesting finding that AHSCT may lead to the re-development of tolerant T cells that respond in a more diverse way to EBV. Knowing this may impact future treatments. 

publications

  • Dyer, Z., Tscharke, D., Sutton, I., & Massey, J. (2023). From bedside to bench: how existing therapies inform the relationship between Epstein–Barr virus and multiple sclerosis. Clinical & translational immunology, 12(2), e1437.   
  • Massey, J., Artuz, C., Dyer, Z., Jackson, K., Khoo, M., Visweswaran, M., … & Sutton, I. (2023). Diversification and expansion of the EBV-reactive cytotoxic T lymphocyte repertoire following autologous haematopoietic stem cell transplant for multiple sclerosis. Clinical Immunology, 254, 109709. 

Updated 31 March 2024 

lead investigator

total funding

$25,000

start year

2023

duration

1 year

STATUS

Past project

Stages of the research process

Fundamental laboratory Research

Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.

Lab to clinic timeline

10+ years

Translational Research

Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.

Lab to clinic timeline

5+ years

Clinical Studies and Clinical Trials

Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.

Lab to clinic timeline

3+ years

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Does stem cell transplant deplete EBV reservoirs in MS?