MECFS Research – Cornell Center for Enervating NeuroImmune Disease

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.

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.

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. Details regarding the agenda and event can be found on the event website. The two-day hybrid event was recorded. Both days of the conference are available below.

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.

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 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.

1 2

Posts navigation