Reactivation of persistent Epstein-Barr virus (EBV) causes secretion of thyrotropin receptor antibodies (TRAbs) in EBV-infected B lymphocytes with TRAbs on their surface

Keiko Nagata, Yuji Nakayama, Katsumi Higaki, Marika Ochi, Kyosuke Kanai, Michiko Matsushita, Satoshi Kuwamoto, Masako Kato, Ichiro Murakami, Takeshi Iwasaki, Eiji Nanba, Hiroshi Kimura, Kazuhiko Hayashi

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV) is a ubiquitous virus that infects most adults latently. It persists in B lymphocytes and reactivates occasionally. Graves' disease is an autoimmune hyperthyroidism caused by thyrotropin receptor antibodies (TRAbs). We have reported that Graves' disease patients and healthy controls have EBV-infected lymphocytes that have TRAbs on their surface (TRAb(+)EBV(+) cells) in peripheral blood mononuclear cells (PBMCs). EBV reactivation is known to be associated with plasma cell differentiation and antibody production of B cells. In this study, we investigated whether TRAb(+)EBV(+) cells really produce TRAbs or not when persistent EBV is reactivated. We cultured PBMCs from 12 Graves' disease patients and 12 healthy controls for several days with cyclosporine A to expand the EBV-infected cell population, and then compared TRAb levels between EBV reactivation by 33°C culture and EBV nonreactivation by 37°C culture of PBMCs. Flow cytometry confirmed that all samples at day 0 (reactivation starting point) contained TRAb(+)EBV(+) cells. During 33°C culture, EBV-reactivated cells with EBV-gp350/220 expression increased from about 1 to 4%. We quantified TRAb levels in culture fluids by radio-receptor assay, and detected an increased concentration for at least one sampling point at 33°C (from days 0 to 12) for all patients and healthy controls. TRAb levels were significantly higher in supernatants of 33°C culture than of 37°C culture, and also significantly higher in supernatants from patients than those from controls. This study revealed TRAb production from TRAb(+)EBV(+) cells in response to reactivation induction of persistent EBV in different efficiencies between patients and controls.

Original languageEnglish
Pages (from-to)328-335
Number of pages8
JournalAutoimmunity
Volume48
Issue number5
DOIs
Publication statusPublished - Aug 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Reactivation of persistent Epstein-Barr virus (EBV) causes secretion of thyrotropin receptor antibodies (TRAbs) in EBV-infected B lymphocytes with TRAbs on their surface'. Together they form a unique fingerprint.

Cite this