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https://www.frontiersin.org/articles/10.3389/fimmu.2018.00229/full
HYPOTHESIS AND THEORY ARTICLE
Front. Immunol., 15 February 2018 | https://doi.org/10.3389/fimmu.2018.00229
Jonas BlomberPhoenix Rising ME / CFS Forumsg1*,
Carl-Gerhard Gottfries2,
Amal Elfaitouri3,
Muhammad Rizwan1 andAnders Rosén4
Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.
- 1Department of Medical Sciences, Uppsala University, Clinical Microbiology, Academic Hospital, Uppsala, Sweden
- 2Gottfries Clinic AB, Mölndal, Sweden
- 3Department of Infectious Disease and Tropical Medicine, Faculty of Public Health, Benghazi University, Benghazi, Libya
- 4Department of Clinical and Experimental Medicine, Division of Cell Biology, Linköping University, Linköping, Sweden
1–3). It often starts with an infection and has a strong tendency to remain a chronic condition.
