A nanoelectronics-blood-based diagnostic biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Abstract

There is not currently a well-established, if any, biological test to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The molecular aberrations observed in numerous studies of ME/CFS blood cells offer the opportunity to develop a diagnostic assay from blood samples. Here we developed a nanoelectronics assay designed as an ultrasensitive assay capable of directly measuring biomolecular interactions in real time, at low cost, and in a multiplex format. To pursue the goal of developing a reliable biomarker for ME/CFS and to demonstrate the utility of our platform for point-of-care diagnostics, we validated the array by testing patients with moderate to severe ME/CFS patients and healthy controls. The ME/CFS samples’ response to the hyperosmotic stressor observed as a unique characteristic of the impedance pattern and dramatically different from the response observed among the control samples. We believe the observed robust impedance modulation difference of the samples in response to hyperosmotic stress can potentially provide us with a unique indicator of ME/CFS. Moreover, using supervised machine learning algorithms, we developed a classifier for ME/CFS patients capable of identifying new patients, required for a robust diagnostic tool.

Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance

“…In a recent study by Davis and colleagues, blood cells from ME patients were reported to display a unique impedance pattern in response to hyperosmotic stress suggesting that a nano-electronic impedance sensor could be used in a diagnostic test for ME (38). We find that the GO: Response to osmotic stress was associated with INMEST treatment, and genes involved include the Bcl2 family member BAX, upon treatment ( Fig.…”

“…It is likely important to improve the diagnostic accuracy of ME and ensure more homogenous group of patients included in order to sharpen our ability to understand the underlying pathology in ME, subdivide patient groups and test treatment strategies in these different subgroups accordingly. The recent advances in diagnostic tests are promising in this regard (38). We hope that this work will inspire others to further investigate the immune/microbe interface and the failure to induce disease tolerance in ME and hopefully this increased attention will lead to some further relief to the millions missing due to this devastating condition.…”

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

“…However, when all three tests were combined using multiple logistic regression, we found very high sensitivity and specificity, with only two from a total of 43 samples (one patient and one control) being misclassified. Except for the recently reported lymphocyte impedance response to salt stress [31], this combination of three tests (lymphocyte death rate, lymphoblast mitochondrial respiratory function and lymphoblast TORC1 activity) thus achieves better accuracy and reliability (sensitivity, specificity and AUC) for discriminating ME/CFS than has been previously reported using other blood-based molecular tests [20][21][22][23].…”

“…For patients, physicians and the health care system, this diagnosis-that depends on exclusion of other illnesses-is a long, frustrating and potentially expensive process. Suitable diagnostic biomarkers have not yet been identified, although a recent report of an altered electrical impedance response to salt stress in patient lymphocytes looks highly promising [31]. We reported, in an accompanying paper, that ex vivo lymphocytes from ME/CFS patients exhibit an elevated death rate in culture after recovery from frozen storage and that lymphoblastoid cell lines (lymphoblasts) isolated from them exhibit multiple mitochondrial and cellular stress signalling abnormalities.…”

“…For these reasons, the search for biomarkers has extended to investigating the utility of routine blood pathology tests, but the results are either inconsistent [9,10] or require further study [30]. The recent development of a nanoneedle bioarray to measure the electrical impedance of ME/CFS peripheral blood mononuclear cells (PBMCs) in plasma is highly promising, but requires identification of the underlying mechanism and proven specificity for ME/CFS [31]. Therefore, the need for a simple blood-based biomarker remains currently unfulfilled.…”