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

Viral Immunology
Keiko NagataKazuhiko Hayashi

Abstract

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 observ...Continue Reading

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Citations

Feb 18, 2020·Rheumatology International·Maria MaślińskaBrygida Kwiatkowska
Jan 8, 2020·Thyroid : Official Journal of the American Thyroid Association·Therese WeiderSara Salehi Hammerstad
Dec 29, 2020·The Journal of Clinical Endocrinology and Metabolism·Therese WeiderSara Salehi Hammerstad
Feb 29, 2020·Best Practice & Research. Clinical Endocrinology & Metabolism·Alessandro AntonelliPoupak Fallahi
Jul 6, 2021·Mediators of Inflammation·Michał OlejarzMarek Ruchała

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Methods Mentioned

BETA
flowcytometry
ELISA

Software Mentioned

SPSS Statistics

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