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.

Graphical abstract by Jessica Maya
Video abstract by Jessica Maya

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.

Arnaud Germain, PhD

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.

Our first EV publication finds disturbances in cytokine networks

Dr. Ludovic Giloteaux

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.

Alexandra Mandarano wins LPS award for JCI publication

Dr. Alexandra Mandarano

Hanson Lab alumna, Alexandra Mandarano ’19 Ph.D., received the Laboratory Product Sales (LPS) award for her December 2019 JCI publication. The LPS award is granted to a student of the graduate field Genomics, Genomics and Development who is first author on what is judged to be the “best” student paper published in a calendar year. The award includes Mandarano’s name engraved on a plaque in the Department of Molecular Biology and Genetics office. Congratulations, Dr. Mandarano!

The Enterovirus Theory of Disease Etiology in ME/CFS: A Critical Review

Adam O’Neal

This methodologically focused review covers aspects of ME/CFS pathophysiology that are consistent with chronic enterovirus infection outcomes and then closely examines the technology used in in past ME/CFS publications to determine how rigorously the enterovirus theory of disease etiology has been investigated.

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.

Maureen Hanson authors editorial on enteroviruses and ME/CFS

Published on August 12, 2021, Maureen Hanson wrote an editorial in Frontiers Science News that highlights the enterovirus theory of ME/CFS. Particularly, Hanson emphasizes that, “ME/CFS is neither a rare nor a trivial illness.” She provides insight into the potential link between ME/CFS and a chronic EV infection. This probable link was reviewed in detail in a Frontiers in Medicine June 2021 article by Adam O’Neal and Hanson. Hanson discusses the possibility that SARS viruses may be the second class of RNA viruses to cause a chronic illness, given the existence of “long COVID.”

Graphical representation of enteroviruses causing brain inflammation. Photo credit: Kateryna Kon (Shutterstock)

Metabolomics study shows disrupted metabolism of acyl lipids and steroids in ME/CFS

Dr. Arnaud Germain

Dr. Arnaud Germain, a member of the Hanson Lab, is the lead author on a new publication in the journal Metabolites. The paper describes a metabolomics study on the plasma of 52 female subjects. A large emphasis on lipids was observed in the approximately 1,750 blood compound datapoints. As summarized in the illustration below, notable changes were uncovered when comparing the ME/CFS and control cohorts.

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