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Multi-omics of iCPET Plasma Samples

This project aims to understand the origin of postural orthostatic tachycardia syndrome (POTS).

    • Wenzhong Xiao, PhD
    • David Systrom, MD
    • Richard Smith, PhD
    • John Jacob, PhD
    • Wei-Jun Qian, PhD
  • The multi-omics of the samples, including cytokines, metabolomics, and proteomics, was completed.
  • There is an enhanced pro-inflammatory cytokine response between the pulmonary and radial arteries in ME/CFS patients compared to symptomatic controls.
  • The small molecule metabolic response to exercise appears comparable or exaggerated between the ME/CFS patients and symptomatic controls, depending upon the computational approach.
  • Proteomic profiles of the radial and pulmonary arteries have been obtained.
  • We have identified the signature of three proteins that distinguish ME/CFS from controls.

We are planning a verification study of the proteomic signature.


POTS is one of the more common symptoms of ME/CFS. This syndrome appears to involve the cardiopulmonary and peripheral vascular systems, both are modulated by the autonomic nervous system. It is unclear why these systems become dysfunctional to cause POTS but understanding the biological pathology underlying it will be relevant to helping understand its relationship to ME/CFS.

Cardiopulmonary exercise testing together with direct measurement through invasive arterial catheters (iCPET) has been useful to define the reason for unexplained dyspnea in general populations thought to be heart or lung in origin. Using this same diagnostic tool, ME/CFS patients have been evaluated and found to demonstrate a preload failure (PLF) pattern under maximum exercise. There are two forms of this PLF that has been observed: low flow and high flow. The low flow phenotype appears to be consistent with a failure of the autonomic nervous system to shift blood from the venous to the arterial side of the circulation or another possibility is a reduced total blood volume. On the other hand, the high flow phenotype appears as an arterial to venous shunt in the peripheral circulation or another possibility is a reduced oxygen delivery to peripheral circulatory beds or a reduced utilization by the mitochondria. 


  1. Systematically study the plasma and phospho-proteome and plasma metabolome in ME/CFS patients using the readily available plasma tissue repository at the Brigham Women’s Hospital to:
    • Determine differentially regulated proteins and peptides.
    • Determine differences in small molecule metabolites.
  1. Conduct proteomic and metabolomic analyses on ME/CFS patient blood samples obtained before, during, and one hour after an iCPET procedure for comparison to those from control volunteers also undergoing iCPET testing.
Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS) Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia Leading Research. Delivering Hope.Open Medicine Foundation®

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