The spread of EBV to ectopic lymphoid aggregates may be the final common pathway in the pathogenesis of ME/CFS
Section snippets
Background
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disorder (or perhaps two or more disorders) that is characterized by severe fatigue and several other symptoms, such as pain, concentration problems, post-exertional malaise, and a persistent or recurrent ‘flu-like’ feeling [1], [2], [3], [4], [5], [6]. It usually starts in adolescence or young adulthood [5]. The etiology is unclear, but many hypotheses have been set forth [7], [8], [9], [10], [11], [12], [13], [14], [15], [16],
Hypothesis
According to the hypothesis that is posited here, ME/CFS develops over 3 steps:
Comparison with some other hypotheses
In a hypothesis about the cause of autoimmune disorders, set forth by Michael Pender [65], [66], EBV and ectopic lymphoid structures play important roles. Pender does not mention ME/CFS, but some of the pathophysiological mechanisms he describes might be relevant also for ME/CFS. However, there are important differences between his hypothesis and the one presented here. In Pender’s hypothesis, autoimmunity (immune processes elicited and orchestrated by autoreactive lymphocytes) plays a central
Formation of ectopic lymphoid aggregates
Ectopic lymphoid aggregates are aggregates of lymphoid cells (B-lymphocytes, T-lymphocytes, dendritic cells) in non-lymphoid tissues [51], [56]. Some of these aggregates are only gatherings of lymphoid cells within a certain area, whereas other aggregates are organized structures with germinal centers. The ectopic lymphoid aggregates seem to form in response to antigenic stimuli [51], [56]. They often develop in tissues that are inflamed because of infectious, autoreactive, or neoplastic
Final remarks
The hypothesis presented here can explain all ME/CFS symptoms. It is also consistent with important research findings. This does not necessarily mean that the hypothesis is valid, however. Future testing is required.
One way to test the hypothesis may be to examine the effects of transferring ex vivo-expanded autologous EBV-specific T-lymphocytes to the patients. There is increasing evidence that EBV-specific T-cell infusions may have good effects on several EBV-related disorders, including
Conflict of interest
No conflict of interest declared.
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