Assessing diagnosis value of miRNA from PBMCs and EVs in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) a debilitating multisystemic disease of unknown etiology, affecting thousands of individuals worldwide, still relies on ruling out medical problems leading to unexplained exertion for its diagnosis due to a complete lack of disease-specific biomarkers. Our group and other, have explored the potential value of microRNA profiles (miRNomes) as diagnostic tools for this disease. However, heterogeneity of participants, low numbers, the variety of samples assayed, and other pre-analytical variables, have hampered the identification disease-associated miRNomes. In this study, our team has evaluated, for the first time, ME/CFS miRNomes in PBMCs and EVs from severely ill patients recruited at the monographic UK ME biobank as a strategy to assess, using SOPs, blood fractions with optimal diagnostic power for a rapid translation of a miR-based diagnostic method into the clinic. Our results show that routine creatine kinase (CK) blood values, plasma EVs physical characteristics (including counts, size and zeta-potential), and a limited number of differentially expressed PBMC and EV miRNAs appear significantly associated with severe ME/CFS (p<0.05). Gene enrichment analysis points to epigenetic and neuroimmune dysregulated pathways, in agreement with previous reports. Population validation by a cost-effective approach limited to these few potentially discriminating variables remains. The samples included in the study consisted on PBMCs (>106 cells) and plasma from 15 severely ill female ME/CFS patients and 15 female, age-population matched healthy subjects, obtained in EDTA blood-collection tubes, by the monographic UK ME Biobank professionals.