Graves' Disease Associated with Infectious Mononucleosis due to Primary Epstein-Barr Virus Infection: Report of 3 Cases

Akatsuka, Hiroshi; Takeshita, Yumie; Saito, Reina; Kaneko, Shuichi; Takamura, Toshinari

doi:10.2169/internalmedicine.49.3978

Cited by 14 publications

(10 citation statements)

References 30 publications

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“…It has been shown that viral infection occasionally induces the production of various autoantibodies, but the titer is not sufficient to lead to clinical manifestations [17]. Nagata et al reported three women with primary EBV infection (age, 19-20 years old) who presented with Graves' disease during the acute phase [18]. TRAb levels were high in all three cases, and a family history of Graves' disease developed in two patients.…”

Section: Discussionmentioning

confidence: 99%

An eight-year-old girl with autoimmune polyglandular syndrome type3A that developed during the course of primary Epstein–Barr virus (EBV) infection: clinical implication of EBV in autoimmune thyroid disease

Kirino

Nakatani

Honma

et al. 2019

Immunological Medicine

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Section: Discussionmentioning

confidence: 99%

An eight-year-old girl with autoimmune polyglandular syndrome type3A that developed during the course of primary Epstein–Barr virus (EBV) infection: clinical implication of EBV in autoimmune thyroid disease

Kirino

Nakatani

Honma

et al. 2019

Immunological Medicine

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“…The possible role of human Herpes viruses in the pathogenesis of autoimmune thyroid diseases is largely unknown and data from one study did not support their association [25]. However, another study indicated that Graves' disease is linked to infectious mononucleosis due to primary Epstein-Barr virus infection in patients [26]. This suggests that both Herpes virus and Influenza A virus can employ similar mechanisms as Epstein-Barr virus to trigger immune activation.…”

Section: Discussionmentioning

confidence: 99%

Microarray profiling and functional analysis of differentially expressed plasma exosomal circular RNAs in Graves’ disease

et al. 2020

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Background: Circulating RNA (circRNA) regulates various bioactivities in cells. A better understanding of the exosomal circRNA can provide novel insights into the pathogenesis and treatment of Graves' disease (GD). We aimed to profile the differentially expressed circRNAs (DEcRs) in plasma exosomes of patients with GD and speculate and probe the functions of the DEcR by comprehensive bioinformatics analyses. Methods: Serum exosomes were isolated from five primary GD patients and five healthy controls via ultracentrifugation. After verification with transmission electron microscopy, exosome samples were subjected to microarray profiling using human circRNA microarrays. Two up-regulated and two down-regulated DEcRs were selected for validation in plasma exosomes from 20 GD and 20 healthy control participants using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The circRNA/microRNA/mRNA interaction network was then assembled and the analysis of the Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was utilized to predict the potential functions of the DEcR associated genes. Results: There were 15 DEcRs revealed in primary GD cases. The intronic circRNA hsa_circRNA_000102 was confirmed as an up-regulated component in plasma exosomes from patients with GD. The circRNA/microRNA/mRNA interaction network unveiled the most potential targeting microRNAs of hsa_circRNA_000102 and its associated genes. The functional analyses predicted involvement of hsa_circRNA_000102 associated genes in pathways of immune system activation, such as viral infection and interferon-beta signaling. Conclusions: hsa_circRNA_000102 is a differentially up-regulated plasma exosomal circRNA in patients with GD. Our study highlights multiple pathways, particularly virus infection and interferon-beta signaling, for mediating immune activation in Graves' disease.

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“…However, there are some cases reported to have developed Graves’ disease related to IM (Akahori et al 2010 ), and this child needs long-term follow-up.…”

Section: Discussion and Evaluationmentioning

confidence: 99%

Production of thyrotropin receptor antibodies in acute phase of infectious mononucleosis due to Epstein–Barr virus primary infection: a case report of a child

et al. 2015

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Various autoantibodies have been reported to be detected during the progression of infectious mononucleosis. We observed a case of infectious mononucleosis due to Epstein–Barr virus primary infection for 2 months, and noticed the transiently increased titer of thyrotropin receptor autoantibodies detected at the acute phase on the 3rd day after admission. At that time, real-time quantitative PCR also revealed the mRNA expressions of an immediate early lytic gene, BZLF1, and a latent gene, EBNA2. The expression of BZLF1 mRNA means that Epstein–Barr virus infects lytically, and EBNA2 protein has an important role in antibody production as well as the establishment of Epstein–Barr virus latency. These results suggest that Epstein–Barr virus lytic infection is relevant to thyrotropin receptor autoantibody production. Thyrotropin receptor autoantibodies stimulate thyroid follicular cells to produce excessive thyroid hormones and cause Graves’ disease. Recently, we reported the thyrotropin receptor autoantibody production from thyrotropin receptor autoantibody-predisposed Epstein–Barr virus-infected B cells by the induction of Epstein–Barr virus lytic infection in vitro. This case showed in vivo findings consistent with our previous reports, and is important to consider the pathophysiology of Graves’ disease and one of the mechanisms of autoimmunity.

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Graves' Disease Associated with Infectious Mononucleosis due to Primary Epstein-Barr Virus Infection: Report of 3 Cases

Cited by 14 publications

References 30 publications

An eight-year-old girl with autoimmune polyglandular syndrome type3A that developed during the course of primary Epstein–Barr virus (EBV) infection: clinical implication of EBV in autoimmune thyroid disease

An eight-year-old girl with autoimmune polyglandular syndrome type3A that developed during the course of primary Epstein–Barr virus (EBV) infection: clinical implication of EBV in autoimmune thyroid disease

Microarray profiling and functional analysis of differentially expressed plasma exosomal circular RNAs in Graves’ disease

Production of thyrotropin receptor antibodies in acute phase of infectious mononucleosis due to Epstein–Barr virus primary infection: a case report of a child

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