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Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls.
Giloteaux, Ludovic; Li, Jiayin; Hornig, Mady; Lipkin, W Ian; Ruppert, David; Hanson, Maureen R.
  • Giloteaux L; Department of Molecular Biology and Genetics, Cornell University, 323 Biotechnology Building, 526 Campus Road, Ithaca, NY, 14853, USA.
  • Li J; Department of Statistics and Data Science, Cornell University, Ithaca, NY, USA.
  • Hornig M; Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA.
  • Lipkin WI; Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, USA.
  • Ruppert D; Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA.
  • Hanson MR; Departments of Neurology and Pathology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
J Transl Med ; 21(1): 322, 2023 05 13.
Article in English | MEDLINE | ID: covidwho-2323268
ABSTRACT

BACKGROUND:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogenous disease characterized by unexplained persistent fatigue and other features including cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Cytokines are present in plasma and encapsulated in extracellular vesicles (EVs), but there have been only a few reports of EV characteristics and cargo in ME/CFS. Several small studies have previously described plasma proteins or protein pathways that are associated with ME/CFS.

METHODS:

We prepared extracellular vesicles (EVs) from frozen plasma samples from a cohort of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) cases and controls with prior published plasma cytokine and plasma proteomics data. The cytokine content of the plasma-derived extracellular vesicles was determined by a multiplex assay and differences between patients and controls were assessed. We then performed multi-omic statistical analyses that considered not only this new data, but extensive clinical data describing the health of the subjects.

RESULTS:

ME/CFS cases exhibited greater size and concentration of EVs in plasma. Assays of cytokine content in EVs revealed IL2 was significantly higher in cases. We observed numerous correlations among EV cytokines, among plasma cytokines, and among plasma proteins from mass spectrometry proteomics. Significant correlations between clinical data and protein levels suggest roles of particular proteins and pathways in the disease. For example, higher levels of the pro-inflammatory cytokines Granulocyte-Monocyte Colony-Stimulating Factor (CSF2) and Tumor Necrosis Factor (TNFα) were correlated with greater physical and fatigue symptoms in ME/CFS cases. Higher serine protease SERPINA5, which is involved in hemostasis, was correlated with higher SF-36 general health scores in ME/CFS. Machine learning classifiers were able to identify a list of 20 proteins that could discriminate between cases and controls, with XGBoost providing the best classification with 86.1% accuracy and a cross-validated AUROC value of 0.947. Random Forest distinguished cases from controls with 79.1% accuracy and an AUROC value of 0.891 using only 7 proteins.

CONCLUSIONS:

These findings add to the substantial number of objective differences in biomolecules that have been identified in individuals with ME/CFS. The observed correlations of proteins important in immune responses and hemostasis with clinical data further implicates a disturbance of these functions in ME/CFS.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Fatigue Syndrome, Chronic / Cytokines Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Humans Language: English Journal: J Transl Med Year: 2023 Document Type: Article Affiliation country: S12967-023-04179-3

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Fatigue Syndrome, Chronic / Cytokines Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Humans Language: English Journal: J Transl Med Year: 2023 Document Type: Article Affiliation country: S12967-023-04179-3