# Immune dysfunction in ME/CFS

> **NIH NIH U54** · CORNELL UNIVERSITY · 2024 · $585,259

## Abstract

PROJECT SUMMARY
ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) remains a prevalent, serious and poorly
understood disease, impacting millions in the USA alone with problems in concentration, memory and sleep
together with musculoskeletal pain. Thus, there is an urgent need to advance our understanding of the basic
science of this disease – as an integral step towards an ultimate cure. Despite our lack of understanding of
ME/CFS, substantial evidence implicates immune dysregulation either as an underlying cause or major
consequence of the disease. Our work has sought to systematically examine gene regulation across the
immune system, with the goal of determining which components are dysregulated in ME/CFS. These studies
have identified classical monocytes, platelets and certain subsets of T cells as the components of the immune
system most severely impacted by ME/CFS. These results establish that immune dysregulation in ME/CFS
involves disparate components of the immune system. Project 3 of our ME/CFS Center has three major goals.
First, to use multiomic approaches to rigorously determine the gene regulatory changes in monocytes in
ME/CFS. To complement these approaches, we will perform monocyte assays to test whether ME/CFS results
in alterations in the ability of monocytes to migrate and differentiate into macrophages, a critical function of
monocytes. Second, we will examine platelet dysregulation in ME/CFS, as our data identifies platelets as
amongst the most dysregulated component of the immune system in ME/CFS, with dysregulation particularly
evident in patients undergoing post-exertional malaise. We hypothesize that platelet defects could contribute to
circulatory and other symptoms in ME/CFS. In this Aim, we will examine the platelet transcriptome, perform
assays to test platelet function, and examine interactions between platelets and other immune cells in
ME/CFS. Third, we will systematically identify ME/CFS specific alterations in signaling across the immune
system. This goal is important, as identification of molecular changes that impact the immune system broadly
are attractive targets for future development of therapies. Achieving these goals has the potential to improve
diagnosis, including generating biomarkers, and will identify specific dysregulated pathways in ME/CFS,
providing a foundation for future development of therapeutics. For example, our first two goals have the
potential to reveal consequential alterations in either (or both) monocytes and platelets in ME/CFS, thereby
establishing a rational path towards eventual treatments or a cure. Because the patient and control cohorts
examined are common across this Center application, we will generate synergistic data from the constituent
projects. In particular, our genomic and functional assays examining monocytes will be paired with profiling of
macrophages in muscle (Project I), which are derived from monocytes in circulation. Similarly, Project II will
examine ...

## Key facts

- **NIH application ID:** 10827463
- **Project number:** 5U54AI178855-07
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** ANDREW W GRIMSON
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $585,259
- **Award type:** 5
- **Project period:** 2017-09-30 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827463

## Citation

> US National Institutes of Health, RePORTER application 10827463, Immune dysfunction in ME/CFS (5U54AI178855-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10827463. Licensed CC0.

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