Table_2_A Systematic Review of the Potential Implication of Infectious Agents in Myasthenia Gravis.XLSX
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.
History
References
- https://doi.org//10.1002/(SICI)1097-4598(200004)23%3A4<453%3A%3AAID-MUS3>3.0.CO;2-O
- https://doi.org//10.1055/s-2004-829593
- https://doi.org//10.1056/NEJMra1602678
- https://doi.org//10.1002/mus.20950
- https://doi.org//10.3390/cells8070671
- https://doi.org//10.3389/fimmu.2020.00707
- https://doi.org//10.1002/ana.410160502
- https://doi.org//10.1111/j.1749-6632.1987.tb51301.x
- https://doi.org//10.1056/NEJM197805182982004
- https://doi.org//10.1056/NEJM198209233071301
- https://doi.org//10.1056/NEJMoa1602489
- https://doi.org//10.1007/BF02242998
- https://doi.org//10.1186/s40425-019-0617-x
- https://doi.org//10.4103/0301-4738.145987
- https://doi.org//10.18632/oncotarget.20731
- https://doi.org//10.4061/2011/213092
- https://doi.org//10.1212/WNL.0b013e3181d7d884
- https://doi.org//10.1002/ana.21902
- https://doi.org//10.1016/j.clineuro.2011.03.019
- https://doi.org//10.1016/j.jneuroim.2009.08.018
- https://doi.org//10.3201/eid2505.181591
- https://doi.org//10.1007/s11940-005-0002-6
- https://doi.org//10.1002/mus.23869
- https://doi.org//10.1212/WNL.0000000000003697
- https://doi.org//10.12659/AJCR.903108
- https://doi.org//10.14740/jocmr2413w
- https://doi.org//10.4049/jimmunol.1402805
- https://doi.org//10.1111/j.1365-2893.1996.tb00106.x
- https://doi.org//10.3201/eid2005.131551
- https://doi.org//10.1023/a%3A1026683007277
- https://doi.org//10.1002/ana.22488
- https://doi.org//10.1097/JTO.0000000000000390
- https://doi.org//10.1177/08830738050200051501
- https://doi.org//10.1159/000117030
- https://doi.org//10.1002/mus.880180819
- https://doi.org//10.1002/mus.20694
- https://doi.org//10.1016/j.jns.2005.08.013
- https://doi.org//10.1159/000115275
- https://doi.org//10.1016/j.imbio.2016.06.012
- https://doi.org//10.1017/S0317167100034119
- https://doi.org//10.1002/mus.20746
- https://doi.org//10.1002/(SICI)1097-4598(199609)19%3A9<1186%3A%3AAID-MUS19>3.0.CO;2-T
- https://doi.org//10.1089/10799900152434321
- https://doi.org//10.1177/096120339700600607
- https://doi.org//10.1159/000050759
- https://doi.org//10.1016/0887-8994(87)90027-0
- https://doi.org//10.1046/j.1440-1754.2000.00477.x
- https://doi.org//10.1111/1759-7714.12953
- https://doi.org//10.1212/WNL.40.4.581
- https://doi.org//10.5692/clinicalneurol.48.666
- https://doi.org//10.1016/j.jaut.2013.12.018
- https://doi.org//10.1097/CND.0b013e3181fb1be7
- https://doi.org//10.1212/WNL.0b013e31820d6290
- https://doi.org//10.1007/s00415-015-7639-1
- https://doi.org//10.2169/internalmedicine.39.490
- https://doi.org//10.1016/j.jhep.2006.08.007
- https://doi.org//10.1111/j.1468-1331.2011.03636.x
- https://doi.org//10.3855/jidc.2061
- https://doi.org//10.1007/s00415-018-8751-9
- https://doi.org//10.3390/v4123701
- https://doi.org//10.1038/nri1201
- https://doi.org//10.1038/35095584
- https://doi.org//10.1016/0092-8674(91)90007-L
- https://doi.org//10.1002/ana.23791
- https://doi.org//10.1016/j.jaut.2013.12.016
- https://doi.org//10.1002/eji.1830250509
- https://doi.org//10.1038/nm.1881