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.
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.
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?
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.
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.
At the Swedish RME annual ME/CFS conference on Oct. 14, 2020, Clinical Core Co-Director, Dr. Betsy Keller, presented virtually on post-exertional malaise (PEM). Keller goes into detail on PEM by covering what it is, ways to assess impairment due to PEM, and strategies to minimize PEM. Her full talk “PEM: Strategies for determining and managing the cardinal symptom of ME/CFS” can be viewed below and is also available on YouTube here.
For an English version of Swedish RME’s website visit this link.
Center Director Dr. Maureen Hanson will be presenting current scientific research on ME/CFS during a panel session hosted by New York State Department of Health (NYS DOH). The session titled “Scientific Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Age of COVID-19” will be moderated by Dr. Charles Gonzalez. Dr. Ian Lipkin (Columbia University) and Dr. Avindra Nath (NIH) will be joining Hanson as panel presenters.
UPDATE: In case you missed the panel discussion, NYS DOH released a recording along with each presenter’s slides. Direct links to the recording and Dr. Hanson’s slides are below. Visit the NYS DOH ME/CFS website for more information.
Jessica Maya, a graduate student in the Genetics, Genomics, and Development Program at Cornell University in Maureen Hanson’s lab, talks about ME/CFS, the immune system response, and the fuels that energize immune cells to properly defend the body. This talk was adapted from Cornell University’s 3 Minute Thesis Finalists Round Competition, where she was tasked to explain her thesis work in under 3 minutes in an engaging form that could be understood by an intelligent audience with no background in the research area.
For the ME International Awareness Day, Director Maureen Hanson is providing a Pecha Kucha on ME/CFS. This is a short video presentation in which 20 slides are presented, automatically changing every 20 seconds. This format has been developed to convey information quickly in a visual manner (see https://www.pechakucha.com/ for more information).