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Solve M.E. Ramsay Researchers Make Strides in Understanding Immune System Reactions that Lead to Chronic Diseases

Solve M.E. supports research into the underlying causes of ME/CFS and Long Covid through the Ramsay Research Grant Program, an open, peer-reviewed competition for grants to support pilot studies and data analysis. The Ramsay Program has been successful in attracting new scientists to the field of ME/CFS, providing much-needed funding for researchers to engage with the science of the disease and build pilot data. 

Below are summaries of recent publications from the Ramsay Researcher network.

  • In their Ramsay-funded study, Eran Segal, PhD, and Thomas Vogl, PhD (Weizmann Institute of Science in Israel) identified signals in the blood of people with severe ME/CFS that might reflect an immune system in overreaction to a protein (called flagellin) commonly found on the surface of bacteria (1). Elevations in anti-flagellin in the blood are consistent with previous findings of “leaky gut”, and gut microbe imbalances and inflammation in people with ME/CFS. The researchers could not use their data alone to create a reliable diagnostic signature for ME/CFS; however, when combined with other standard lab results from the blood samples, they were able to improve diagnosis predictions, relative to using either data source alone.
  • In a hypothesis paper (2), Manuel Ruiz-Pablo (European University of Madrid, Ramsay 2019 grantee) argues that a link exists between immune cells with weak protection against Epstein-Barr virus (EBV) infection and the development of some chronic diseases. This weak protection is inherited through genes and, when someone is infected with EBV, might result in chronic immune dysfunction or inflammatory processes. A Ramsay-supported study led by Bruno Paiva, PhD (University of Navarra in Spain) and Ruiz-Pablo is directly testing this hypothesis in the context of ME/CFS.
  • Aaron Ring, MD, PhD, (Yale University, Ramsay 2021 grantee) and collaborators from Yale and Mount Sinai published evidence that lingering virus, reactivation of EBV, and chronic inflammation play a role in Long COVID (3). The researchers didn’t find clear signs that the immune system is targeting healthy human tissue; however, these findings don’t rule out the possibility that autoimmunity is a feature for some people. Dr. Ring will be able to compare the Long COVID results to his ongoing Ramsay study with Jillian Jaycox, PhD, which is focused on autoimmunity signals in people with ME/CFS.
  • Nitric-oxide is a compound important to the proper function of the endothelium, a layer of cells that line blood vessels and play a key role in blood moving smoothly through the body. Francisco Westermeier, PhD (FH JOANNEUM University of Applied Sciences in Austria, Ramsay 2019 grantee) found in a small pilot study that endothelial cells exposed to plasma from ME/CFS patients produced less NO (4). In his Ramsay-funded study, Dr. Westermeier is leading a team in an even more comprehensive analysis of biochemical pathways that might be responsible for endothelial dysfunction in ME/CFS. 

  1. Vogl (2022). Systemic antibody responses against human microbiota flagellins are overrepresented in chronic fatigue syndrome patients. Science Advances. https://doi.org/10.1126/sciadv.abq2422
  2. Ruiz-Pablo (2022). CD4+ Cytotoxic T Cells Involved in the Development of EBV-Associated Diseases. Pathogens. https://doi.org/10.3390/pathogens11080831
  3. Klein, et al (2022). Distinguishing features of long Covid identified through immune profiling. MedRxiv. https://doi.org/10.1101/2022.08.09.22278592
  4. Bertinat, et al (2022). Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients. Vascular Pharmacology. https://doi.org/10.1016/j.vph.2022.106953
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