Tag: mecfs

Extracellular Vesicle Study Sheds New Light on ME/CFS Biology

Researchers from the Center for Enervating Neuroimmune Disease have published a new study investigating extracellular vesicle (EV) proteins in ME/CFS. The research, published in Clinical and Translational Medicine, represents an important analysis of blood-derived EVs and their potential role in ME/CFS.

The study, led by Center Investigators Katherine Glass and Ludovic Giloteaux, analyzed plasma samples from 10 male ME/CFS patients and 12 age- and BMI-matched healthy sedentary male controls before, 15 minutes after, and 24 hours after a maximal exercise challenge, and is an extension of a prior study in an all-female cohort.

Graphical Abstract by Ludovic Giloteaux, Ph.D.

The researchers identified significant differences in EV protein cargo between ME/CFS patients and healthy controls at baseline. However, EV protein profiles in ME/CFS patients and controls showed the most pronounced differences 15 minutes post-exercise. ME/CFS subjects’ showed reduced EV protein levels related to energy metabolism, including the TCA cycle; immune overactivation, particularly in the complement system; and disruptions in protein homeostasis. Strikingly, changes in proteins involved in the endoplasmic reticulum (ER) stress response during the 24 hour recovery phase strongly correlated with post-exertional malaise (PEM) severity. We also observed dysregulation in protein homeostasis and ER stress response proteins in the female study. Notably, while EV protein dynamics in healthy controls correlated with exercise physiology metrics like VO₂ peak and ventilatory anaerobic threshold, these associations were absent in ME/CFS patients, suggesting a disruption in EV-mediated physiological adaptation. Together, these findings provide molecular insight into the mechanisms driving symptom exacerbation after exertion in ME/CFS.

This open access study, which represents an important step forward in understanding the molecular basis of ME/CFS, is freely available to read. The findings advance our understanding of how extracellular vesicles, important cellular messengers, may contribute to disease mechanisms in ME/CFS and suggest new directions for future research into diagnostic biomarkers and therapeutic targets.

To promote scientific collaboration and data transparency, the complete protein abundance data for each protein and subject has been made available through mapMECFS.

New Study Explores Autoantibody Profiles in ME/CFS Using Advanced Screening Technologies

Researchers from the Cornell Center for Enervating Neuroimmune Disease, Fred Hutchinson Cancer Center, Yale School of Medicine, and Augmenta Bioworks have published a study investigating autoantibody patterns in ME/CFS. The research, published in the International Journal of Molecular Sciences, represents an in-depth look at the involvement of autoimmunity in ME/CFS.

The study examined blood samples from a substantial cohort of 172 participants who were evaluated at multiple sites across the US. All ME/CFS patients met the Canadian Consensus Criteria for diagnosis and developed their condition prior to 2020, ensuring their illness was not related to the COVID-19 pandemic.

Using two sophisticated platforms – a 1,134 autoantibody Luminex panel and Rapid Extracellular Antigen Profiling (REAP) – researchers examined over 7,500 antibody-antigen interactions. Unlike previous studies, this comprehensive analysis found no significant differences in autoantibody reactivities between ME/CFS patients and controls. This includes previously reported targets such as β-adrenergic receptors and other G protein-coupled receptors. The results indicate that the role of autoantibodies in ME/CFS needs further investigation.

The paper is available through open access, and we encourage those interested to read the full publication for more detailed information.

Graphical abstract by Arnaud Germain, Ph.D.

New Research Links T Cell Exhaustion to ME/CFS

A new study from our Center, recently published in the Proceedings of the National Academy of Sciences (PNAS), has revealed important insights into how ME/CFS affects the immune system. The research team, led by Associate Director Andrew Grimson, discovered that patients with ME/CFS show signs of T cell exhaustion, a condition where immune cells become less effective at fighting infections. This finding helps to better understand the chronic nature of the disease and may open new paths for treatment approaches.

Fig. 5 Model of proposed ME T cell mechanism of action via exhaustion.
Source: PNAS publication

The Cornell Chronicle has published an accompanying article about this research, offering a detailed look at the study’s implications for ME/CFS patients. The article explains how the research team conducted their investigation and what these findings might mean for future treatment strategies. You can read the full Cornell Chronicle coverage to learn more about this significant development in ME/CFS research.

Comparing IACCs is essential to make progress on all

Peluso, Hanson, and Deeks present a compelling Viewpoint in Science Translational Medicine, exploring infection-associated chronic conditions (IACCs). The article begins by addressing the complexities of studying IACCs. It then delves into a notable historical account of chronic conditions linked to infections, emphasizing the lessons these histories offer for advancing Long Covid research. The authors highlight the importance of avoiding past mistakes and adopting a measured, objective approach.

One key recommendation is to use what we already know about IACCs, such as ME/CFS, to inform Long Covid research. The authors also emphasize the importance of recognizing disease subtypes and accounting for sex differences in research.

Distinguishing between IACCs can be particularly challenging when the underlying cause is unknown. The authors propose using well-characterized patient populations from various IACCs and studying them under the same protocol to identify both overlaps and differences. Such comprehensive studies could clarify how these conditions relate to one another.

In addition to research, the authors stress the urgent need for clinical treatments for IACCs. They outline ongoing clinical trials and suggest focusing on approaches that consider viral persistence, immune dysfunction, and combination therapies.

Hanson presents on immune exhaustion at IIMEC16

At the 16th Invest in ME Research International ME Conference (IIMEC16), Maureen Hanson presented on immune system dysfunction in ME/CFS. Her talk, which is available on YouTube, discusses findings that relate to T cell metabolism, gene expression, and epigenetics. The overall outlook points to an “exhausted” immune cell state.

More information about the conference can be found on the IIMEC16 website.

Recruitment information for muscle and cellular function study

We are seeking volunteers comprising 40 ME/CFS patients and 20 controls to participate in an NIH funded (U54AI178855) project. An overview of the study can be found here. Only those participants whose onset of ME/CFS was before 2020 will be eligible. Please review our recruitment flyer for more information on how to volunteer as a patient or control in this research study.

Large CPET publication describes the physiological component of post-exertional malaise in ME/CFS

Out in the Journal of Translational Medicine, Betsy Keller et al. describes results from the Center’s large multi-site 2-day CPET study. The publication analyzes cardiopulmonary exercise testing (CPET) data collected over two days from 84 individuals with ME/CFS and 71 sedentary controls. Within this population, 55 sex, age, and fitness-matched pairs were also compared. This is the largest 2-day CPET study of ME/CFS to date.

The article provides robust documentation of impaired recovery in people with ME/CFS following exertion (i.e., post-exertional malaise), something that is not seen in the control population. The study also recruited sedentary controls and used sex, age, and fitness-matched pairs to validate that fitness level does not predispose someone with ME/CFS to exertion intolerance. Keller et al. highlights that the autonomic nervous system is, at least partly, associated with ME/CFS due to the disrupted hemodynamic and ventilatory responses to exertion. Additionally, the worsening of CPET parameters over the two-day protocol led to increased clinical impairment status in ME/CFS whereas controls remain relatively the same.

Overall, the manuscript provides a detailed look at the physiological component of post-exertional malaise in ME/CFS. The paper is open access. Individuals interested in the topic should check out the full publication for more information.

Center investigators present at International ME/CFS & Long COVID Conference

Center investigators presented at the 1st International Conference on Clinical and Scientific Advances in ME/CFS and Long COVID. The two-day hybrid event was recorded. Videos from both conference days are included below, with additional information available on this website. 

Day 1 (April 3, 2024): Dr. Susan Levine presented “Brief History of ‘Pandemics’ Related to ME/CFS Punta Gorda Florida and Royal Free Hospital in London. Origin of Current Case Definition.” Her talk starts at 27:00. Dr. Levine also took part in a panel discussion and “Conversation: The Role of Physician as Advocate, Lessons Learned from 30 Years of Clinical Practice” that occurred later in the day.

Day 2 (April 4, 2024): Dr. Maureen Hanson presented “Circulating Signals of ME/CFS.” Her talk starts at 6:07:00.

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.

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