Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Version 1 : Received: 2 February 2020 / Approved: 3 February 2020 / Online: 3 February 2020 (10:36:05 CET)



A peer-reviewed article of this Preprint also exists. Missailidis, D.; Sanislav, O.; Allan, C.Y.; Annesley, S.J.; Fisher, P.R. Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int. J. Mol. Sci. 2020, 21, 1142. Missailidis, D.; Sanislav, O.; Allan, C.Y.; Annesley, S.J.; Fisher, P.R. Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int. J. Mol. Sci. 2020, 21, 1142. Copy Journal reference: Int. J. Mol. Sci. 2020, 21

DOI: 10.3390/ijms21031142

Cite as: Missailidis, D.; Sanislav, O.; Allan, C.Y.; Annesley, S.J.; Fisher, P.R. Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int. J. Mol. Sci. 2020, 21, 1142. Missailidis, D.; Sanislav, O.; Allan, C.Y.; Annesley, S.J.; Fisher, P.R. Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int. J. Mol. Sci. 2020, 21, 1142. Copy CANCEL COPY CITATION DETAILS

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating illness whose biomedical basis is now beginning to be elucidated. We reported previously that, after recovery from frozen storage, lymphocytes (peripheral blood monocytic cells, PBMCs) from ME/CFS patients die faster in culture medium than those from healthy controls. We also found that lymphoblastoid cell lines (lymphoblasts) derived from these PBMCs exhibit multiple abnormalities in mitochondrial respiratory function and signalling activity by the cellular stress-sensing kinase TORC1. These differences were correlated with disease severity, as measured by the Richardson and Lidbury Weighted Standing Test. The clarity of the differences between these cells derived from ME/CFS patient blood and those from healthy controls suggested that they may provide useful biomarkers for ME/CFS. Here we report a preliminary investigation into that possibility using a variety of analytical classification tools, including linear discriminant analysis, logistic regression and Receiver Operating Characteristic (ROC) curve analysis. We found that results from three different tests, lymphocyte death rate, mitochondrial respiratory function and TORC1 activity could each individually serve as biomarker with better than 90% sensitivity but only modest specificity vís a vís healthy controls. However, in combination they provided a cell-based biomarker with sensitivity and specificity approaching 100% in our sample. This level of sensitivity and specificity was almost equalled by a suggested protocol in which the frozen lymphocyte death rate was used as a highly sensitive test to triage positive samples to the more time consuming and expensive tests measuring lymphoblast respiratory function and TORC1 activity. This protocol provides a promising biomarker that could assist in more rapid and accurate diagnosis of ME/CFS.

Subject Areas

Myalgic Encephalomyelitis; Chronic Fatigue Syndrome; mitochondria; Complex V; TORC1; Seahorse respirometry; biomarker; diagnosis; ME/CFS

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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