ME Research UK — Energising ME Research

Unravelling the aetiology of post-exertional malaise in ME/CFS: the role of intracellular immunity and sensory processing

Investigator

Dr Jo Nijs

Institution

Department of Human Physiology, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels; and Division of Musculoskeletal Physiotherapy, Department of Health Sciences, University College Antwerp, Antwerp, Belgium

Aims

In people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), only a small number of studies have examined more than one body system concurrently. The present study will examine the interaction and contribution of two apparently unrelated body systems (i.e., the immune system and central nervous system) to post-exertional malaise and exercise incapacity in people with ME/CFS. In people with ME/CFS, the immune system is further deregulated by too vigorous exercise, and elastase activity has been identified as an important determinant of exercise performance. G-actin, a calpain substrate playing a crucial role in antigen presentation and T-cell signalling, is cleaved in patients with ME/CFS. It is hypothesised that too vigorous exercise triggers elastase activity and G-actin cleavage in people with ME/CFS, while symptoms and immune status remain unaffected in healthy subjects and people with ME/CFS performing a self-paced and physiologically limited bout of exercise. In relation to the central nervous system, the observed decreased pain threshold during exercise in ME/CFS patients is indicative of a dysfunctional central anti-nociceptive mechanism, and may account in part for the post-exertional malaise experienced by people with ME/CFS. Finally, the present study design allows for examining dynamic immune-to-central nervous system communication pathways in people with ME/CFS.

Methods

Twenty-two women with ME/CFS and 22 healthy controls will be subjected to a one-week baseline activity monitoring, pain threshold measurement, blood sampling for determination of elastase activity and G-actin cleavage, assessment of their health status (questionnaires), and a submaximal exercise test with cardiorespiratory monitoring and lactate determination. The pre-exercise assessments will be repeated at 1 hour and 24 hours post-exercise, and subjects will be asked to wear an accelerometer continuously between the first and second testing day. On day 14 of the trial, the study participants will be subjected to the same protocol, but this time they will perform a bicycle exercise with three ‘safety breaks’ (i.e., exercise limits): heart rate, exercise duration and workload will be individually tailored.