title: Thyrotropin Receptor Antibody (TRAb)-IgM Levels Are Markedly Higher Than TRAb-IgG Levels in Graves' Disease Patients and Controls, and TRAb-IgM Production Is Related to Epstein-Barr Virus Reactivation.
abstract: Graves' disease is an autoimmune thyroid disorder that mainly presents as hyperthyroidism and is caused by thyrotropin receptor antibodies (TRAbs) that stimulate thyroid-stimulating hormone receptors. We previously reported that Graves' disease patients and healthy controls both had Epstein-Barr virus (EBV)-infected TRAb-positive B cells and the EBV-reactivated induction of these B cells in cultures may induce the production of TRAbs. In the present study, we quantified serum TRAb-IgG and TRAb-IgM levels in 34 Graves' disease patients and 15 controls using ELISA to elucidate the mechanisms underlying EBV-related antibody production. As expected, TRAb-IgG and TRAb-IgM levels were higher in Graves' disease patients than in controls; however, TRAb-IgM levels were significantly higher than those of TRAb-IgG levels, whereas total IgM levels were lower than total IgG levels. On the other hand, the enhanced production of TRAb-IgM was frequently observed in patients with EBV reactivation. These results are consistent with the fact that the percentage of autoreactive IgM B cells are higher than that of autoreactive IgG B cells, and support the EBV-related polyclonal B cell activation. It is necessary to clarify the biological characteristics of TRAb-IgM and the relationship between TRAb isotypes and the biology of Graves' disease.
authors.affiliation: 1 Division of Molecular Pathology, Department of Pathology, Faculty of Medicine, Tottori University , Yonago, Japan .
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kumata
authors.affiliation: 1 Division of Molecular Pathology, Department of Pathology, Faculty of Medicine, Tottori University , Yonago, Japan .
authors.forename: Keiko
authors.initials: K
authors.lastname: Nagata
authors.affiliation: 1 Division of Molecular Pathology, Department of Pathology, Faculty of Medicine, Tottori University , Yonago, Japan .
authors.forename: Michiko
authors.initials: M
authors.lastname: Matsushita
authors.affiliation: 1 Division of Molecular Pathology, Department of Pathology, Faculty of Medicine, Tottori University , Yonago, Japan .
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuwamoto
authors.affiliation: 1 Division of Molecular Pathology, Department of Pathology, Faculty of Medicine, Tottori University , Yonago, Japan .
authors.forename: Masako
authors.initials: M
authors.lastname: Kato
authors.affiliation: 2 Department of Pathology, Kochi Medical School , Nankoku, Japan .
authors.forename: Ichiro
authors.initials: I
authors.lastname: Murakami
authors.affiliation: 3 Internal Medicine, Kuma Hospital , Kobe, Japan .
authors.forename: Shuji
authors.initials: S
authors.lastname: Fukata
authors.affiliation: 1 Division of Molecular Pathology, Department of Pathology, Faculty of Medicine, Tottori University , Yonago, Japan .
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi