Epstein-Barr virus reactivation in peripheral B lymphocytes induces IgM-type thyrotropin receptor autoantibody production in patients with Graves' disease. 2023

Keiko Nagata, and Kazuhiko Hayashi, and Keisuke Kumata, and Yukio Satoh, and Mitsuhiko Osaki, and Yuji Nakayama, and Satoshi Kuwamoto, and Yoshinori Ichihara, and Tsuyoshi Okura, and Kazuhiko Matsuzawa, and Junichiro Miake, and Shuji Fukata, and Takeshi Imamura
Division of Pharmacology, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan.

Epstein-Barr virus (EBV) is a human herpes virus that latently infects B lymphocytes. When EBV is reactivated, host B cells differentiate into plasma cells and produce IgM-dominant antibodies as well as many progeny virions. The aims of the present study were to confirm the IgM dominance of thyrotropin-receptor antibodies (TRAbs) produced by EBV reactivation and investigate the roles of TRAb-IgM in Graves' disease. Peripheral blood mononuclear cells (PBMCs) containing TRAb-producing cells were stimulated for EBV reactivation, and TRAb-IgM and TRAb-IgG were measured by ELISA. TRAb-IgM were purified and TSH-binding inhibitory activities were assessed using a radio-receptor assay. Porcine thyroid follicular epithelial cells were cultured with TRAb-IgM and/or complements to measure the intracellular levels of cAMP and the amount of LDH released. TRAb-IgM/TRAb-IgG (the MG ratio) was examined in sequential serum samples of Graves' disease and compared among groups of thyroid function. The results obtained showed that IgM-dominant TRAb production was induced by EBV reactivation. TRAb-IgM did not inhibit TSH binding to TSH receptors and did not transduce hormone-producing signals. However, it destroyed thyroid follicular epithelial cells with complements. The MG ratio was significantly higher in samples of hyperthyroidism or hypothyroidism than in those with normal function or in healthy controls. A close relationship was observed between TRAb-IgM produced by EBV reactivation and the development and exacerbation of Graves' disease. The present results provide novel insights for the development of prophylaxis and therapeutics for Graves' disease.

UI MeSH Term Description Entries
D007075 Immunoglobulin M A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally was called a macroglobulin. Gamma Globulin, 19S,IgM,IgM Antibody,IgM1,IgM2,19S Gamma Globulin,Antibody, IgM
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D008135 Long-Acting Thyroid Stimulator An immunoglobulin G, often found in the blood of hyperthyroid individuals. It stimulates the thyroid for a longer duration than does thyrotoxin and may cause hyperthyroidism in newborns due to placental transmission. LATS,Thyroid Stimulating Hormone Receptor Autoantibodies,Thyroid Stimulating Hormone Receptor Autoantibody,Thyroid Stimulator, Long-Acting,Thyrotropin Receptor Antibodies,Thyrotropin Receptor Antibody,Thyrotropin Receptor Autoantibodies,Thyrotropin Receptor Autoantibody,Antibody, Thyrotropin Receptor,Autoantibody, Thyrotropin Receptor,Long Acting Thyroid Stimulator,Receptor Antibody, Thyrotropin,Receptor Autoantibody, Thyrotropin,Thyroid Stimulator, Long Acting
D011989 Receptors, Thyrotropin Cell surface proteins that bind pituitary THYROTROPIN (also named thyroid stimulating hormone or TSH) and trigger intracellular changes of the target cells. TSH receptors are present in the nervous system and on target cells in the thyroid gland. Autoantibodies to TSH receptors are implicated in thyroid diseases such as GRAVES DISEASE and Hashimoto disease (THYROIDITIS, AUTOIMMUNE). Receptors, Thyroid Stimulating Hormone,TSH Receptors,Thyroid Stimulating Hormone Receptors,Thyrotropin Receptors,LATS Receptors,Receptor, LATS Immunoglobulins,Receptors, LATS,Receptors, Long-Acting Thyroid Stimulator,Receptors, TSH,TSH Receptor,Thyroid Stimulating Hormone Receptor,Thyrotropin Receptor,Receptor, TSH,Receptor, Thyrotropin,Receptors, Long Acting Thyroid Stimulator
D004854 Herpesvirus 4, Human The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies. Burkitt Herpesvirus,Burkitt Lymphoma Virus,E-B Virus,EBV,Epstein-Barr Virus,Human Herpesvirus 4,Infectious Mononucleosis Virus,Burkitt's Lymphoma Virus,HHV-4,Herpesvirus 4 (gamma), Human,Burkitts Lymphoma Virus,E B Virus,E-B Viruses,Epstein Barr Virus,Herpesvirus, Burkitt,Infectious Mononucleosis Viruses,Lymphoma Virus, Burkitt,Mononucleosis Virus, Infectious,Mononucleosis Viruses, Infectious
D006111 Graves Disease A common form of hyperthyroidism with a diffuse hyperplastic GOITER. It is an autoimmune disorder that produces antibodies against the THYROID STIMULATING HORMONE RECEPTOR. These autoantibodies activate the TSH receptor, thereby stimulating the THYROID GLAND and hypersecretion of THYROID HORMONES. These autoantibodies can also affect the eyes (GRAVES OPHTHALMOPATHY) and the skin (Graves dermopathy). Basedow's Disease,Exophthalmic Goiter,Goiter, Exophthalmic,Graves' Disease,Basedow Disease,Hyperthyroidism, Autoimmune,Basedows Disease,Disease, Basedow,Disease, Basedow's,Disease, Graves,Disease, Graves',Exophthalmic Goiters,Goiters, Exophthalmic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001323 Autoantibodies Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them. Autoantibody
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent

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