A Systematic Review of the Potential Implication of Infectious Agents in Myasthenia Gravis

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. To provide a synthesis of the evidence examining infectious agents associated with the onset of MG. 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. We searched PubMed and Web of Science. Papers captured through database searching ( = 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. 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. 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.