Epstein–Barr Virus Lytic Reactivation Induces IgG4 Production by Host B Lymphocytes in Graves' Disease Patients and Controls: A Subset of Graves' Disease Is an IgG4-Related Disease-Like Condition
| Autor: | Hirotsugu Sugihara, Shunsuke Tanio, Kazuhiko Hayashi, Yuji Nakayama, Sayuri Hara, Masako Kato, Katsumi Higaki, Kiyosuke Ishiguro, Keiko Nagata, Michiko Matsushita, Satoshi Kuwamoto |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Epstein-Barr Virus Infections Herpesvirus 4 Human Graves' disease Plasma cell Antibodies Viral medicine.disease_cause Autoimmunity Epstein–Barr virus 0302 clinical medicine hemic and lymphatic diseases IgG4-related disease skin and connective tissue diseases B-Lymphocytes integumentary system biology Thyroid Middle Aged Graves Disease medicine.anatomical_structure 030220 oncology & carcinogenesis RNA Viral Molecular Medicine Female Antibody Adult Immunology Virus Autoimmune Diseases Young Adult 03 medical and health sciences Virology parasitic diseases medicine Humans business.industry fungi Epstein–Barr virus reactivation Original Articles medicine.disease Epstein–Barr virus-encoded small RNA1 030104 developmental biology Case-Control Studies Immunoglobulin G biology.protein Virus Activation Immunoglobulin G4-Related Disease business |
| Zdroj: | Viral Immunology |
| ISSN: | 1557-8976 0882-8245 |
| Popis: | Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory disease with characteristic histological findings and high serum IgG4 levels. Epstein–Barr virus (EBV) is a persistent herpesvirus in B lymphocytes, and we previously reported EBV reactivation-induced Ig production. We showed that EBV reactivation induced the production of thyrotropin receptor antibodies, the causative antibodies of Graves' disease. In the present study, we investigated whether EBV reactivation induced IgG4 production and if EBV-positive B cells or IgG4-positive plasma cells are present in the thyroid tissues of Graves' disease patients with lymphoplasmacytic infiltration. EBV-encoded small RNA1 (EBER1) in situ hybridization and immunohistochemistry for IgG and IgG4 were performed on seven resected thyroid tissues with lymphoplasmacytic infiltration collected from the thyroids of 11 Graves' disease patients. We then cultured the lymphocytes of 13 Graves' disease patients and 14 controls and induced EBV reactivation to measure IgG4 levels in culture fluids. We detected EBER1-positive cells and IgG4-positive plasma cells in the same area of thyroid tissues. EBV-reactivated cells with IgG4 on their surface were observed in culture cells, and IgG4 production was detected in culture fluids. The IgG4/IgG percentage was higher than that in normal serum level. A subset of Graves' disease is an IgG4-RD-like condition, not an IgG4-RD. EBV reactivation stimulates IgG4 production, which may result in high serum IgG4 levels and promote IgG4-positive plasma cell infiltration. EBER1 needs to be examined when an increase in IgG4-positive plasma cell numbers is noted. |
| Databáze: | OpenAIRE |
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