mecfs – Page 2 – Cornell Center for Enervating NeuroImmune Disease

Recovery from two-day CPET in ME/CFS

Cardiopulmonary exercise testing (CPET) was an integral part of our NIH-funded collaborative research center (CRC). The Cornell CRC used the CPET as a way to interrogate the hallmark symptom of ME/CFS—post-exertional malaise (PEM). CPET-associated samples are being analyzed to uncover the molecular basis of PEM. This molecular work gave us the opportunity to explore other aspects of PEM such as recovery following exertion.

Dr. Geoffrey Moore, M.D., Cornell CRC Clinical Core Co-director, led an effort to describe CPET recovery in ME/CFS. This work is now available in the journal Medicina under the title Recovery from Exercise in Persons with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The paper documents a significant difference in recovery between sedentary controls (~2 days) and people with ME/CFS (~13 days). Moore et al. studied 84 people with ME/CFS and 60 controls using a self-reported symptom severity questionnaire. Both female and male participants from three different test sites across the United States were included in the study. The publication is open access so check it out for more information.

Urine metabolomics shows divergent response to exercise between people with ME/CFS and sedentary controls

We have a new study published today that compares metabolite levels in urine of ME/CFS patients and sedentary controls before and after cardiopulmonary exercise testing (CPET).

Katie Glass is lead author of Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients. The study is available online in the International Journal of Molecular Sciences and full text is open access.

As shown in the graphical abstract above and explained in the video abstract below, we found a large number of metabolites at increased concentrations in the urine of controls 24 hours after CPET compared to baseline. However, we did not find significant changes in levels of any metabolites in the urine of ME/CFS patients after CPET.

When we looked at which metabolites were changing differently in ME/CFS patients and controls after exercise, we found the most compounds in the amino acid and lipid metabolic superpathways.

Overall, our data suggests that the metabolisms of sedentary controls undergo major changes that allow them to recover from exertion, while ME/CFS patients fail to make similar adaptive responses. This dysfunctional metabolic excretion could be contributing to exercise intolerance in ME/CFS patients.

Check out the paper to see many more results, including individual compounds that are significantly different between patients and controls and altered correlations between urine and plasma metabolites.

Video abstract by Katie Glass

Fatty Acid Oxidation in ME/CFS Immune Cell Populations

A new publication from the Center on fatty acid oxidation in immune cells has appeared today. Jessica Maya is the lead author of Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome published in the International Journal of Molecular Sciences.

As discussed in the paper, there is more evidence for abnormal immunometabolism in ME/CFS. Maya utilized her expertise in flow cytometry and Seahorse flux analysis to demonstrate this dysfunction. She isolated natural killer (NK), helper T (CD4), and cytotoxic T (CD8) cell populations from both healthy donors and people with ME/CFS. These immune cell populations were studied in their circulating state and after stimulation. The stimulation process aims to mimic an immune response. Maya’s findings showed that all three of the cell types have an increased use of fats to power their activities when compared to healthy donors. Her results show that ME/CFS immune cells have a greater reliance on fats for energy when they are stimulated. Overall, these findings support the presence of an altered metabolic state in certain immune cells in individuals with ME/CFS.

Maya outlines these findings in her graphical and video abstracts inserted below.

Video abstract by Jessica Maya

A commentary by Andrew Grimson about the single-cell RNA-seq preprint from his lab

When we started this project, our goal was to ask which components of the immune system are most altered in ME/CFS (and which are not). If we could answer this question, we hoped that it would give us a clear path towards understanding some of the molecular underpinnings of ME/CFS, which is likely to be an essential step towards therapies. We used a technique called single-cell RNA sequencing to answer this question, an approach that looks at the genes expressed in thousands of individual cells from each ME/CFS individual (and control). When we look at the data (which in aggregate contains about 0.5 million immune cells found in peripheral blood, sampled from 30 ME/CFS individuals and 28 controls), the strongest signal of dysregulation is found in classical monocytes, a type of innate immune cell with diverse roles. There are three fundamental observations we can make about monocytes in ME/CFS. First, within individuals with ME/CFS, the proportion of monocytes that are dysregulated is variable, with a mixture of relatively normal cells and those that are altered. Second, comparing between individuals, the proportion of altered monocytes is also variable, with individuals with a higher fraction of altered monocytes tending to have more serious cases of ME/CFS. Third, by looking at the genes mis-expressed in altered monocytes, we can find patterns that suggest what might be different about the biology of the altered monocytes. In essence, what we see is that monocytes in individuals with ME/CFS appear to be triggered to migrate to tissues, where they become macrophages. This migration and differentiation pathway is a normal function of monocytes – we think the pathway is more active in ME/CFS, and this increased activity could contribute to many of the symptoms of ME/CFS. This work sets up lots of questions that motivate our work now – where are the monocytes going in ME/CFS individuals, what is causing them to be dysregulated, and ultimately, can we reverse this dysregulation?

Letter to the Editor of Metabolites explaining the estimate of 65 million people with ME/CFS worldwide

Back in January 2020, Germain et al published a metabolomics paper in Metabolites stating:

The latest worldwide prevalence rate projects that over 65 million patients suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)…

This 65 million people with ME/CFS figure has brought about some attention resulting in this letter to the Editor. Importantly, this letter brings several more supporting references beyond the initial Valdez et al publication. The key takeaway from the letter is that the prevalence of ME/CFS is likely much greater than the oft-cited figure of “20 million worldwide.”

Plasma proteomics publication shows disrupted cell-to-cell signaling

We are proud to announce our latest plasma proteomics publication is available as open access in Proteomes.

This manuscript takes a look at 4,790 circulating plasma proteins from 20 ME/CFS women compared to 20 healthy women, over an unprecedented range, for ME/CFS, of 9 orders of magnitude.

Pathway analysis uncovered disrupted cell-to-cell communication, specifically in the ephrin-Eph signaling pathway. This pathway is crucial for many aspects of our body’s homeostasis, including development, physiology, and disease regulation.

Additionally, the paper outlines promising results for the development of a diagnostic test using protein ratios.

First author, Arnaud Germain, PhD, outlines these findings in a video abstract below.

Transcripts for the video are available:
– English
– German

Chinese, French, and Spanish subtitles for the video abstract are available. See video settings to select an option.

RTI launches two tools to advance ME/CFS research

Our MECFSnet collaborator, RTI, which operates the Data Management and Coordinating Center (DMCC) for the NIH ME/CFS Centers, has officially launched two research tools – mapMECFS and searchMECFS.

With mapMECFS, the Cornell ME/CFS Collaborative Research Center has worked promptly to submit data to the network. A total of 8 datasets are available. Below lists the publications from which the datasets have been uploaded.

Read more to see the full announcement from RTI.

Continue reading “RTI launches two tools to advance ME/CFS research”

CDC SEC call on Immune Dysfunction in ME/CFS

On September 23, 2020, a CDC ME/CFS Stakeholder Engagement and Communication (SEC) call took place, featuring a presentation by Dr. Maureen Hanson, ENID Center Director, on “Immune Dysfunction in ME/CFS”. Dr. Elizabeth Unger, Branch Chief of CDC’s Chronic Viral Diseases Branch, provided CDC programmatic updates. The SEC call transcript, audio, and presentation slides are now available on the CDC’s website. Direct links to specific content, including Hanson’s slideshow presentation, are below.

Listen to the audio recording.

Read the transcript.

View Dr. Hanson’s presentation.

Maureen Hanson presents at Cornell COVID-19 Summit 2020

On November 4-5, 2020, Cornell University and Weill Cornell Medicine held a COVID-19 Summit to exchange information about research into the disease ongoing at both institutions. Dr. Maureen Hanson presented a “flash” talk with three slides to introduce Cornell COVID-19 researchers to the similarity between long-haul COVID-19 and ME/CFS. Content from Hanson’s talk is below.

Our first EV publication finds disturbances in cytokine networks

Center investigator Dr. Ludovic Giloteaux is lead author of a new publication out in the Journal of Translational Medicine. The paper describes cytokine profiling in extracellular vesicles (EVs) in ME/CFS. The study specifically looks at EVs from the plasma of 70 participants, 35 of which are diagnosed with ME/CFS and compared with 35 healthy controls. Both female and male participants were included in this work. Dr. Jesus Castro-Marrero visited our lab from Spain on a fellowship to contribute to the project.

One key finding of the study is the noted disturbances in cytokine networks.. Disturbances in these cytokine networks were seen in both plasma and EVs, and provides further evidence of immune dysregulation in ME/CFS. We are using information from this work to inform our further studies on EVs from blood collected before and after an exercise challenge. Stay tuned for future publications from our Center on this topic.

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