Journal
FRONTIERS IN NEUROLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fneur.2021.618021
Keywords
myasthenia gravis; autoimmunity; infection; virus; etiology
Categories
Funding
- National Institutes of Health (T35)/Boehringer Ingelheim Veterinary Scholars Research Training Program
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The study aimed to investigate the association of infectious agents with the onset of myasthenia gravis (MG), with a hypothesis that microbes play a pathogenic role in initiating MG. Among 827 papers screened, 42 met the inclusion and exclusion criteria, and the infected patients with Epstein-Barr virus, human papillomavirus, and poliovirus showed the highest integrated metric of evidence (IME) values. The overall lack of evidence for a causal link between microbes and MG highlights the need for further mechanistic studies in this area.
Background: Myasthenia gravis (MG) is an autoimmune disorder of unknown etiology in most patients, in which autoantibodies target components of neuromuscular junctions and impair nerve to muscle transmission. Objective: To provide a synthesis of the evidence examining infectious agents associated with the onset of MG. Hypothesis: We hypothesized that microbes play a pathogenic role in the initiation of MG. For clinical cases, the onset of clinical signs is used as a proxy for the true onset of autoimmunity. Methods: We searched PubMed and Web of Science. Papers captured through database searching (n = 827) were assessed, yielding a total of 42 publications meeting the inclusion and exclusion criteria. An additional 6 papers were retrieved from the reference lists of relevant articles. For each pathogen, an integrated metric of evidence (IME) value, from minus 8 to plus 8, was computed based on study design, quality of data, confidence of infectious disease diagnosis, likelihood of a causal link between the pathogen and MG, confidence of MG diagnosis, and the number of infected patients. Negative IME values corresponded to studies providing evidence against a role for microbes as triggers of MG. Results: One hundred and sixty-nine myasthenic patients infected with 21 different pathogens were documented. Epstein-Barr virus (median = 4.71), human papillomavirus (median = 4.35), and poliovirus (median = 4.29) demonstrated the highest IME values. The total median IME was 2.63 (mean = 2.53; range -3.79-5.25), suggesting a general lack of evidence for a causal link. Conclusions: There was a notable absence of mechanistic studies designed to answer this question directly. The question of the pathogenic contribution of microbes to MG remains open.
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