High anti-EBNA-1 IgG levels are associated with early-onset myasthenia gravis.
BACKGROUND
Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against the acethylcholine receptor (AchR) of the neuromuscular junction in the majority of patients.


METHODS
Here, we examined IgG antibodies against the type 1 nuclear antigen of Epstein-Barr virus (EBNA-1) in the sera of 158 patients with MG compared to 184 healthy controls.


RESULTS
Although serum concentration in the sera was not different, high anti-EBNA-1 IgG titers (above 90th percentile of the normal values) were more common in the patients (26.6 vs. 16.3%, P=0.024). In addition, high EBNA-1 IgG levels occurred more frequently amongst the 94 patients with early-onset myasthenia gravis (EOMG, 30.8%) as compared to the 64 patients with late-onset disease (LOMG, 14.1%) (P=0.021). Using multiple logistic regression, high serum concentration of the anti-EBNA-1 IgG antibodies was significantly associated with EOMG (OR: 3.17, P=0.027), even after adjustment for sex, presence/absence of anti-AchR antibodies and presence/absence of anti-Titin antibodies. Out of 39 patients with EOMG, who underwent thymectomy, 18 patients (46%) had thymoma, 6 had thymic hyperplasia (15%), and 15 patients had thymic atrophy (39%); there was no difference comparing EBNA-1 antibody titers in the sera. As no correlation was found between the titers of anti-AchR, anti-Titin, and EBNA-1 antibodies, a dysregulated heterogeneous B-cell response was unlikely to be responsible for the elevated levels of EBV-associated antibody in patients.


CONCLUSIONS
In summary, our data suggest that high levels of EBNA-1 antibodies are more common in MG compared to healthy controls and are especially associated with EOMG.
3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
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Csuka
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Banati
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Rozsa
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Füst
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Illes
D000328:Adult; D000368:Aged; D064211:Connectin; D004185:Disability Evaluation; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005260:Female; D006801:Humans; D006814:Hungary; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000276:immunology; D009157:Myasthenia Gravis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D011494:Protein Kinases / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D064211:Connectin; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; C577285:TTN protein, human; D011494:Protein Kinases; C417029:EBV-encoded nuclear antigen 1