New insights into ME/CFS using a multiomic approach
A new open access publication in the Journal of Translational Medicine describes the work by Giloteaux et al. to uncover ways to detect the disease ME/CFS. Ludovic Giloteaux and Jiayin Li, joint first authors, took a collaborative approach to improve our understanding of ME/CFS. Giloteaux isolated extracellular vesicles from the plasma of 98 Chronic Fatigue Initiative individuals (49 ME/CFS and 49 controls) to study their signaling molecules (i.e., cytokines). Then he worked with Jiayin Li and David Ruppert, statisticians at Cornell, and using data generated by Columbia University investigators, the group combined plasma cytokine, EV cytokine, plasma proteomic, and demographic datasets to explore new ways to approach ME/CFS.
One of the key findings from the publication is the 86% accuracy in differentiating between people with ME/CFS and health controls. Giloteaux et al. leveraged multiple datasets to achieve this goal. The paper also outlines interesting correlations between various biological molecules and clinical surveys that measure disease severity. For example, higher levels of pro-inflammatory molecules (e.g., CSF2 & TNFa) were correlated with greater physical and fatigue symptoms in people with ME/CFS.
The publication is open access so see the website for more information. Additionally, the EV cytokine data is available on mapMECFS.
Center receives 5-year NIH collaborative research center award
Announced April 11, 2023, the ENID Center has successfully competed for a 5-year U54 award from the National Institutes of Health. The U54 award provides funding for a multidisciplinary, multicomponent collaborative research center. The award will fund exciting research to explore topics such as endothelium function, cell-free RNA, immune cell dysfunction, extracellular vesicles, and more.
The new research award includes a subject participation component. We will soon provide information on how interested people can get involved. Check back here later, or stay tuned to the Center’s tweets and Facebook posts for updates.
The new funding is partly an extension of previous work. Specifically, we plan to utilize previous and future data, highlighted in the figure below, to perform multiomic analyses. Multiomics uses sophisticated computation approaches to incorporate multiple datasets, which can provide an enhanced and holistic perspective.
The Cornell Chronicle first announced the U54 award. Check out the press release for more information.
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.
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.
A commentary by Andrew Grimson about the single-cell RNA-seq preprint from his lab
IACFS/ME’s October 2022 Journal Club features Arnaud Germain
Arnaud Germain, Center investigator, was featured at IACFS/ME’s October 2022 Journal Club. Germain presented and discussed his longitudinal ME/CFS metabolomics publication.
Head over to YouTube to watch the video using this link.
IACFSME Conference 2022
IACFSME held a virtual medical and scientific research conference on July 27-30, 2022. Our Center presented several talks and participated in the poster session at the conference. Center members Andrew Grimson, Arnaud Germain, Betsy Keller, Geoff Moore, Jessica Maya, and Katie Glass gave oral presentation on topics ranging from immune cell exhaustion to post CPET recovery. Postdoctoral associate, Ludovic Giloteaux, presented a poster on extracellular vesicle proteins in plasma. Details about the conference agenda can be found on the event’s website.
We would also like to announce that Candace Receno, a new collaborator at Ithaca College, and Jessica Maya received the NIH NINDS travel award at this year’s meeting. Congratulations to Candace and Jessica!
Survey of Anti-Pathogen Antibody Levels in ME/CFS
The Center would like to announce a serology publication that is open access in Proteomes.
This study, led by Adam O’Neal, analyzed plasma antibodies to 122 different pathogen antigens in a case-control comparison including 103 individuals. The cohort of 59 ME/CFS and 44 healthy controls included both female and male participants. The anti-pathogen antibody assays were performed by Augmenta Bioworks. Although this study did not find one particular pathogen associated with ME/CFS, sex-based differences were uncovered. Check out this publication (link above) for more information.
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.