Detection of human parvovirus B19 infection in the thymus of patients with thymic hyperplasia-associated myasthenia gravis

Abstract

ObjectiveTo investigate the association between myasthenia gravis (MG) and human parvovirus B19 (B19V) infection in the thymus. MethodsThe presence of human B19V DNA and protein was assessed in 138 samples—including 68 thymic hyperplasias (39 with MG), 58 thymomas (23 with MG), and 12 normal thymus tissues—using a nested polymerase chain reaction, immunohistochemistry, laser capture microdissection, and sequencing in a double-blinded manner. ResultsB19V DNA was detected mainly in thymic hyperplasia, and the positivity rate (41.18%, 28/68) was significantly higher than that in thymoma (3.45%, 2/58) (p <0.001) but not that in normal thymic tissues. Correspondingly, the positivity rate in thymic hyperplasia with MG (30.77%, 12/39) was significantly higher than that in thymoma with MG (4.35%, 1/23) (p=0.021). However, it was higher in thymic hyperplasia without MG (55.17%, 16/29) than in thymic hyperplasia with MG (30.77%, 12/39) (p=0.043). Cells in thymic hyperplasia positive for B19V VP1/VP2 protein (63.24%, 43/68) were identified mainly in ectopic germinal centres and thymic corpuscle epithelial cells, but were rare in thymomas (1.72%, 1/58) (p <0.001). Moreover, the positivity rate was significantly higher in thymic hyperplasia with MG (74.36%, 29/39) than in thymic hyperplasia without MG (48.28%, 14/29) (p=0.027). ConclusionsTo our knowledge, the present study is the first to show that human B19V infection is closely associated with thymic hyperplasia and thymic-hyperplasia-associated MG, but is not related to thymoma or thymoma-associated MG. The findings reveal a previously unrecognized aetiopathogenic mechanism of thymic-hyperplasia-associated MG, evoking numerous questions that require further investigation.