Intrathymic Epstein-Barr virus infection is not a prominent feature of myasthenia gravis

Ann Neurol. 2011 Sep;70(3):508-14. doi: 10.1002/ana.22488.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Age of Onset
  • Antigens, CD19 / metabolism
  • B-Lymphocytes / physiology
  • Cell Lineage / physiology
  • Cytokines / metabolism
  • DNA, Viral / chemistry
  • Enzyme-Linked Immunosorbent Assay
  • Epstein-Barr Virus Infections / pathology
  • Epstein-Barr Virus Infections / virology*
  • Female
  • Flow Cytometry
  • Humans
  • Hyperplasia / pathology
  • Immunohistochemistry
  • Male
  • Myasthenia Gravis / pathology
  • Myasthenia Gravis / virology*
  • Plasmids / genetics
  • Receptors, Cholinergic / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymectomy
  • Thymus Gland / pathology
  • Thymus Gland / virology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Young Adult


  • Adrenal Cortex Hormones
  • Antigens, CD19
  • Cytokines
  • DNA, Viral
  • Receptors, Cholinergic
  • Tumor Necrosis Factor Receptor Superfamily, Member 7