title: Intrathymic Epstein-Barr virus infection is not a prominent feature of myasthenia gravis.
abstract: 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.
authors: Department of Neuroinflammation, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
authors: Kristina
authors: K
authors: Kakalacheva
authors: Michael A
authors: MA
authors: Maurer
authors: Björn
authors: B
authors: Tackenberg
authors: Christian
authors: C
authors: Münz
authors: Nick
authors: N
authors: Willcox
authors: Jan D
authors: JD
authors: Lünemann
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D017668:Age of Onset; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000821:virology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D009157:Myasthenia Gravis / Q000473:pathology / Q000821:virology*; D010957:Plasmids / Q000235:genetics; D011950:Receptors, Cholinergic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013934:Thymectomy; D013950:Thymus Gland / Q000473:pathology / Q000821:virology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D018941:Antigens, CD19; D016207:Cytokines; D004279:DNA, Viral; D011950:Receptors, Cholinergic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7