# Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights

## TL;DR

The study uses serum proteomics to uncover widespread protein changes in ME/CFS patients, revealing immune and metabolic disruptions that could inform future treatments.

## Contribution

The work identifies novel proteomic signatures in ME/CFS, including tissue-specific shifts and immune reprogramming patterns.

## Key findings

- 1,823 aptamers showed significant differences between ME/CFS patients and healthy controls.
- Immune reprogramming is indicated by reduced proteins from activated neutrophils.
- Proteomic patterns suggest regulatory networks involving immune, vascular, and metabolic dysfunction.

## Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition often triggered by infections, with unclear mechanisms and no established biomarkers or treatments. We apply aptamer-based serum proteomics to 50 ME/CFS patients and 29 healthy controls, analyzing 7,326 protein targets. We identify 1,823 aptamers with significant differences between the groups (845 after false discovery rate [FDR] correction). Distinct patterns of tissue- and process-specific changes are seen. There is a broad increase in secreted proteins, while intracellular proteins, e.g., from skeletal muscle, particularly show reduction. Immune cell-associated signatures indicate immune reprogramming, including a distinct reduction in proteins secreted by activated neutrophils. Focused secretome analysis supports intensified regulatory interactions related to immune activity, inflammation, vasculature, and metabolism. Validation of measurements using antibody-based methods confirms findings for a selection of proteins. The uncovered serum proteome patterns in ME/CFS patients may contribute to understanding the pathophysiology and inform future biomarker research and therapeutic development.

•Serum proteomics reveals widespread protein changes in ME/CFS patients•Tissue-linked shifts show reduced intracellular and increased secreted proteins•Immune signatures show reprogramming with reduced neutrophil-derived proteins•Regulatory networks link immune, vascular, and metabolic dysfunction

Serum proteomics reveals widespread protein changes in ME/CFS patients

Tissue-linked shifts show reduced intracellular and increased secreted proteins

Immune signatures show reprogramming with reduced neutrophil-derived proteins

Regulatory networks link immune, vascular, and metabolic dysfunction

Hoel et al. characterize circulating proteomic signatures in ME/CFS and identify widespread tissue-linked alterations, including increased secreted proteins and reduced intracellular proteins. Protein changes affecting immune, metabolic, and vascular processes support immune reprogramming and define regulatory networks that provide pathobiological insight relevant to biomarker development and future therapeutic strategies.