Title:The Reification of the Clinical Diagnosis of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) as an Immune and Oxidative Stress Disorder: Construction of a Data-driven Nomothethic Network and Exposure of ME/CFS Subgroups
Volume: 21
Issue: 16
Author(s): Michael Maes*, Marta Kubera, Kristina Stoyanova and Jean-Claude Leunis
Affiliation:
- Department of Psychiatry, Medical University of Plovdiv, Plovdiv,Bulgaria
Keywords:
Depression, Neuroimmune, Inflammation, Oxidative and nitrosative stress, Autoimmune, Bacterial translocation.
Abstract: The approach towards myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
remains in a permanent state of crisis with fierce competition between the psychosocial school,
which attributes ME/CFS to the perception of effort, and the medical approach (Maes and Twisk,
BMC Med, 2010, 8, 35). The aim of this paper is to review how to construct a nomothetic model of
ME/CFS using Partial Least Squares (PLS) path analysis and ensembling causome (bacterial translocation
as assessed with IgM/IgA responses to LPS), protectome (lowered coenzyme Q10), adverse
outcome pathways (AOP) including increased lysozyme, CD38+ T cell activation, cell-mediated
immune activation (CMI), and IgM responses to oxidative specific epitopes and NO-adducts
(IgM OSENO).Using PLS, we trained, tested and validated this knowledge- and data-driven causal
ME/CFS model, which showed adequate convergence, construct and replicability validity.This bottom-
up explicit data model of ME/CFS objectivates the descriptive narratives of the ME/CFS
phenome, using causome-protectome-AOP data, whereby the abstract concept ME/CFS is translated
into pathways, thereby securing the reification of the ME/CFS phenome. We found that 31.6%
of the variance in the physiosomatic symptom dimension of ME/CFS was explained by the cumulative
effects of CMI and CD38+ activation, IgM OSENO, IgA LPS, lysozyme (all positive) and
coenzyme Q10 (inversely). Cluster analysis performed on the PLS-generated latent vector scores
of all feature sets exposed three distinct immune groups of ME/CFS, namely one with increased lysozyme,
one with increased CMI + CD38 activation + depressive symptoms, and another with increased
bacterial translocation + autoimmune responses to OSENO.
