Charles B Hillier

Myalgic Encephalomyelitis, or Chronic Fatigue Syndrome (ME/CFS), is a disease of uncertain origin. Studies of Norwegian health records have suggested that ME/CFS incidence across age groups is bimodal—a characteristic that could provide insight into the aetiology of the disease. Here, we analysed survey data from over 9000 respondents with ME/CFS from 10 European countries, and observe an early onset peak with a mean of 16.0 years old (standard deviation [SD]: 4.3) and a late onset peak at 36.6 years old (SD: 10.5). Statistical support for multimodal onset age was evident in 7 of the 10 countries examined. Infection as a trigger for ME/CFS was 10 percentage points higher among early compared to late onset disease (p = 2.1 × 10−13). Early onset ME/CFS was associated with greater odds of being severely or very severely affected (OR = 2.15, 95% CI [1.84–2.51], p < 2 × 10−16). Those with first degree relatives with ME/CFS had greater odds of early than late onset ME/CFS (OR = 1.43, 95% CI [1.25–1.63], p = 4.4 × 10−07). We further validated our findings in a UK dataset where we replicated bimodal onset age and observed significantly greater odds of glandular fever/infectious mononucleosis as a trigger in early onset cases (OR = 2.32, 95% CI [1.99–2.71], p = 2.4 × 10−24). Our findings suggest that incidence of ME/CFS peaks in adolescence and in early middle-age and that early onset ME/CFS is more common in those with affected relatives, more often triggered by infection, and associated with more severe disease.

Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome is a disease of uncertain aetiology that affects up to 400,000 individuals in the UK. Exposure of cultured cells to the sera of people with ME has been proposed to cause phenotypic changes in these cells in vitro when compared to sera from healthy controls. ME serum factors causing these changes could inform the development of diagnostic tests. In this study, we performed a large-scale, pre-registered replication of an experiment from Fluge et al (2016) that reported an increase in maximal respiratory capacity in healthy myoblasts after treatment with serum from people with ME compared to serum from healthy controls. We replicated the original experiment with a larger sample size, using sera from 67 people with ME and 53 controls to treat healthy cultured myoblasts, and generated results from over 1,700 mitochondrial stress tests performed with a Seahorse Bioanalyser. We observed no significant differences between treatment with ME or healthy control sera for our primary outcome of interest, oxygen consumption rate at maximal respiratory capacity. Results from our study provide strong evidence against the hypothesis that ME blood factors differentially affect healthy myoblast mitochondrial phenotypes in vitro .