Dysregulation of EV protein cargo in ME/CFS females in response to maximal exercise

Exertion intolerance and post-exertional malaise are defining features of ME/CFS. Work from our Center aims to uncover the molecular disruption that occurs during and around these features. Thus, through the lens of extracellular vesicles (EVs), a publication from co-lead authors Ludovic Giloteaux and Katherine Glass provides novel insights into these topics.

The study involved the isolation of EVs, membrane-bound non-replicating particles released from cells, from the plasma of 18 ME/CFS and 17 healthy control female participants. The cargo of EVs are relevant in that they provide signals that could uncover elements of dysfunction in ME/CFS. Specifically, protein cargo from EVs were examined in this publication before and after a cardiopulmonary exercise test (i.e., around the induction of PEM).

Figure 1 from the publication provides an overview of the study’s experimental design

The EV proteome in response to exercise was clearly different in ME/CFS when compared to sedentary controls. These divergent responses were associated with different molecular pathways. Uncovered protein differences between the cohorts also point to contrasting tissues and cell types.  Additionally, there were several proteins associated with a worsening of muscle pain (e.g., THBS1 and TPM4), PEM (e.g., NEXN), and fatigue (e.g., CLU) post exercise in ME/CFS. Although it is difficult to directly associate changes with the EV proteome to distinct cell types, this publication brings forth avenues to interrogate further.

If you are interested in more information regarding this publication, the entire paper is freely available in the Journal of Extracellular Vesicles.

Center participates in the NIH ME/CFS Research Roadmap series

The working group of the National Advisory Neurological Disorders and Stroke Council, part of the National Institutes of Health, recommended the development of research priorities for ME/CFS to help move the field towards translational research and clinical trials. The result led to creation of the ME/CFS Research Roadmap Working Group. The Group, co-led by Drs. Lucinda Bateman and Maureen Hanson, produced a series of eight webinars. A complete description of the webinar series can be found on the ME/CFS Research Roadmap website.

Our Center’s mission is to promote research to identify its cause(s), biomarkers, and pathophysiology in order to lead to prevention and effective treatments. With this focus, several Center investigators presented data to support the development of research priorities for ME/CFS. The talks from our Center are included below.

Maureen Hanson presented “ Immune cell-type approaches to identify mechanisms of ME/CFS” during the Immune System webinar. Her talk starts at 1:38:40.

Jessica Maya presented “Investigations and Consequences of Altered Metabolism in ME/CFS Immune Cells” during the Metabolism webinar. Her talk starts at 58:32.

Maureen Hanson presented “Chronic infection in ME/CFS: non-Herpes viruses” during the Chronic Infections webinar. Her talk starts at 1:01:25.

Ludovic Giloteaux presented “Extracellular vesicles” during the Physiology webinar. His talk starts at 3:15:10.

The NIH ME/CFS Center presents lectures at “Advancing ME/CFS Research: Identifying Targets for Intervention and Learning from Long COVID”

NIH held a hybrid online conference on the NIH campus on December 11-12, 2023.  Center personnel attending in person were  Claire McNally, Annie Gardella, David Iu, Jessica Maya, Tien Luyen (“Louis”) Vu, Katherine Glass, Arnaud Germain, Ludovic Giloteaux, Dawei Li, Andrew Grimson, and Maureen Hanson, as well as collaborator Nicholas Hampilos from Weill Cornell Medicine.

Both days of the conference are available online.

Videocast Day 1

Jessica Maya’s presentation “Investigating T cell populations for immune cell dysfunction in ME/CFS” starts at 3:50:10.

Videocast Day 2

Maureen Hanson’s presentation on “ME/CFS and long COVID: similarities and differences” starts at 1:03:00.

Andrew Grimson’s presentation on “Monocyte dysregulation in ME/CFS” starts at 1:37:35.

Nicholas Hampilos’ presentation on “Effect of Physical Exertion on CNS Oxidative Stress and Metabolism in ME/CFS” starts at 2:56:53.

Center trainees participate in the Symposium For Promoting The Advancement Of Research Knowledge In ME/CFS (SPARK ME)

NIH sponsored an early career researchers workshop on December 10, 2023 attended by Cornell graduate students Claire McNally Annie Gardella, and David Iu, postdoctoral associates Jessica Maya and Tien Luyen (“Louis”) Vu, and Research Associates Katherine Glass, Arnaud Germain and Ludovic Giloteaux.  Drs. Glass and Maya helped organize the meeting.

Verbal presentations:

David Iu: Epigenetic Reprogramming of CD8+ T cell Populations Drives Exhaustion in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Tien Luyen Vu: Single-cell transcriptomics of ME/CFS circulating immune system before and after symptom provocation

Poster presentations:

Anne Gardella: Cell-free RNA signatures of myalgic encephalomyelitis/ chronic fatigue syndrome

Ludovic Giloteaux: Extracellular vesicle protein cargo in ME/CFS cases and controls following maximal exercise

Arnaud Germain: Proteomic adjustments following induction of post-exertional malaise

Claire McNally: Investigating the role of iNOS in endothelial dysfunction in ME/CFS

International ME/CFS Awareness Day 2022: metabolite disruption in ME/CFS

For International ME/CFS Awareness Day, we would like to announce the official publication of a large metabolomics study from our Center. The work led by Arnaud Germain, PhD, describes results from a longitudinal plasma metabolite study associated with a 2-day cardiopulmonary exercise test (CPET). Over 100 individuals, including both females and males, were assayed before and after both days of the 2-day CPET. The article is open access in the journal JCI Insight. The quote below, from this publication, does an excellent job at summarizing the study.

Our longitudinal study design has allowed us to identify a number of pathways that diverge between healthy individuals and those with ME/CFS 24 hours after an exercise challenge, at which time patients typically experience PEM. Inability to recover properly after exertion is one of the most disabling symptoms of ME/CFS. Our study provides insight into the metabolic changes that are inimical to proper response to physical effort.

“Next Steps for ME/CFS Research”

Dr. Maureen Hanson

Dr. Maureen Hanson spoke on the “Next Steps for ME/CFS Research” panel at the NIH meeting “Accelerating Research on ME/CFS” on April 5, 2019.  The text of her statement and some by Dr. Jose Montoya on the same panel can be found here.  A transcript of the prior remarks at the meeting by Dr. Francis Collins is available here.

Outreach in Japan

Image Credit: admissions.oist.jp

This past November, @DrMaureenHanson visited the Okinawa Institute of Science and Technology Graduate University in Japan to participate in their distinguished speaker series. Dr. Hanson’s talk provided general awareness about ME/CFS and shared details on the Center’s research. In particular, the research topics covered were the functioning of immune cells, cellular metabolism, the microbiome, neuroimaging, and exercise physiology.  While in Japan, Dr. Hanson spoke with a representative of the Japan ME Association.  ME/CFS researchers in Japan hope to attend the April 2019 NIH meeting.

Scroll to top