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Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model
Uppsala Univ, Sweden.
Gottfries Clin AB, Sweden.
Benghazi Univ, Libya.
Uppsala Univ, Sweden.
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2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 229Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2018. Vol. 9, article id 229
Keywords [en]
chronic fatigue syndrome; myalgic encephalomyelitis; irritable bowel syndrome; postexertional malaise; autoimmunity
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-145446DOI: 10.3389/fimmu.2018.00229ISI: 000425152100001OAI: oai:DiVA.org:liu-145446DiVA, id: diva2:1192904
Note

Funding Agencies|SolveME/CFS Initiative; Swedish ME Association; Open Medicine Foundation [1011454]; Uppsala Academic Hospital [FOU2017-0039]; Invest in ME Foundation, London

Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-04-13

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Rosén, Anders
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