期刊
ANNALS OF NEUROLOGY
卷 70, 期 3, 页码 508-514出版社
WILEY-BLACKWELL
DOI: 10.1002/ana.22488
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资金
- UK Medical Research Council
- Life Science Zurich Graduate School
- National Cancer Institute [R01CA108609, R01CA101741]
- Foundation for the National Institutes of Health
- Swiss National Science Foundation [310030_126995]
- Swiss National Research Foundation
- Gemein-nutzige Hertie Foundation
- Swiss Multiple Sclerosis Foundation
- Betty and David Koetser Foundation
- Ernst Schering Foundation
- Baxter Research Grant Program
- Swiss National Science Foundation (SNF) [310030_126995] Funding Source: Swiss National Science Foundation (SNF)
Lymph node-type T-and B-cell infiltrates with germinal centers are characteristic features of the hyperplastic thymus in early onset myasthenia gravis (EOMG). Epstein-Barr virus (EBV) infection confers survival advantages on B cells, and has recently been implicated in tertiary lymphoid tissue formation in EOMG. We evaluated the frequency of intrathymic EBV-infected B-lineage cells and antiviral immune responses in treatment-naive patients with EOMG. Real-time polymerase chain reaction was performed to quantify the content of genomic EBV DNA (BamHI-W repeat region) in thymic cell suspensions. Serial paraffin sections of EOMG thymi were analyzed for the presence of EBV-encoded RNA by in situ hybridization and for viral gene expression by immunohistochemistry. Humoral and cellular immune responses to viral antigens were quantified by enzyme-linked immunosorbent assay and flow cytometry-based intracellular cytokine staining. We detected minimal levels of viral DNA-corresponding to single viral genomes-in only 6 of 16 hyperplastic EOMG thymi, indicating extreme rarity of viral copy numbers in the investigated thymic samples. That was confirmed by similar rarity of EBV-encoded RNA and viral proteins identified in thymic sections. Furthermore, EBV-specific T-and B-cell responses were unchanged in patients with EOMG. These findings do not support an etiologic role for EBV in the initiation of EOMG. ANN NEUROL 2011;70:508-514
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