Yersinia enterocolitica envelope proteins that are crossreactive with the thyrotropin receptor (TSHR) also have B-cell mitogenic activity

Hongwei Zhang, Indreshpal Kaur, David W. Niesel, Gattadahalli Seetharamaiah, Johnny W. Peterson, Louis B. Justement, Bellur S. Prabhakar, Gary R. Klimpel

Research output: Contribution to journalArticle

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Abstract

Autoantibodies to the thyrotropin receptor (TSHR) have been shown to mediate the hyperthyroidism associated with Graves' disease (GD). A number of hypotheses have been proposed which link an infectious agent to the mechanism(s) involved in the induction of GD. Several studies have suggested that the development of GD may be linked to infection with the enteric pathogen Yersinia enterocolitica. We have recently identified two low molecular weight (5.5 and 8 kDa) envelope proteins of Y. enterocolitica that are crossreactive with the extracellular domain of human TSHR (ETSHR). In this study, we have purified these ETSHR-crossreactive Yersinia proteins (TSHR-CRP) and have further characterized their immunoreactivity. Both the 5.5 and 8 kDa TSHR-CRPs were shown to be mitogenic for mouse spleen cells. This mitogenic activity was specific for B cells and was not due to lipopolysaccharide (LPS) contamination. TSHR-CRPs were mitogenic for LPS-non-responsive spleen cells obtained from C3H/Hej mice, and polymyxin B did not inhibit the mitogenic activity of the TSHR-CRPs. TSHR-CRPs also induced high levels of IL-6 production in B cells and induced production and secretion of significant levels of IgG and IgM. Finally, culture supernatants from TSHR-CRP-stimulated spleen cells were shown by Western blot analysis to contain antibodies that recognized the ETSHR. These results identify for the first time two envelope proteins of Yersinia that have mitogenic activity and therefore could represent important proteins involved in the pathogenesis of Yersinia infections. Because these mitogenic proteins also contain epitopes crossreactive with the TSHR, they are potentially important for advancing our understanding of the role molecular mimicry plays in the induction of autoimmunity to the TSHR.

Original languageEnglish (US)
Pages (from-to)509-516
Number of pages8
JournalJournal of Autoimmunity
Volume9
Issue number4
DOIs
StatePublished - Aug 1996
Externally publishedYes

Fingerprint

Thyrotropin Receptors
Yersinia enterocolitica
B-Lymphocytes
Yersinia
Graves Disease
Proteins
Spleen
Lipopolysaccharides
Yersinia Infections
Molecular Mimicry
Polymyxin B
Inbred C3H Mouse
Hyperthyroidism
Autoimmunity
Autoantibodies
Immunoglobulin M
Epitopes
Interleukin-6
Immunoglobulin G
Molecular Weight

Keywords

  • Antibody
  • Autoimmunity
  • Bacteria
  • Grave's disease
  • IL-6
  • Mitogen
  • Thyrotropin receptor
  • Yersinia

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Yersinia enterocolitica envelope proteins that are crossreactive with the thyrotropin receptor (TSHR) also have B-cell mitogenic activity. / Zhang, Hongwei; Kaur, Indreshpal; Niesel, David W.; Seetharamaiah, Gattadahalli; Peterson, Johnny W.; Justement, Louis B.; Prabhakar, Bellur S.; Klimpel, Gary R.

In: Journal of Autoimmunity, Vol. 9, No. 4, 08.1996, p. 509-516.

Research output: Contribution to journalArticle

Zhang, Hongwei ; Kaur, Indreshpal ; Niesel, David W. ; Seetharamaiah, Gattadahalli ; Peterson, Johnny W. ; Justement, Louis B. ; Prabhakar, Bellur S. ; Klimpel, Gary R. / Yersinia enterocolitica envelope proteins that are crossreactive with the thyrotropin receptor (TSHR) also have B-cell mitogenic activity. In: Journal of Autoimmunity. 1996 ; Vol. 9, No. 4. pp. 509-516.
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abstract = "Autoantibodies to the thyrotropin receptor (TSHR) have been shown to mediate the hyperthyroidism associated with Graves' disease (GD). A number of hypotheses have been proposed which link an infectious agent to the mechanism(s) involved in the induction of GD. Several studies have suggested that the development of GD may be linked to infection with the enteric pathogen Yersinia enterocolitica. We have recently identified two low molecular weight (5.5 and 8 kDa) envelope proteins of Y. enterocolitica that are crossreactive with the extracellular domain of human TSHR (ETSHR). In this study, we have purified these ETSHR-crossreactive Yersinia proteins (TSHR-CRP) and have further characterized their immunoreactivity. Both the 5.5 and 8 kDa TSHR-CRPs were shown to be mitogenic for mouse spleen cells. This mitogenic activity was specific for B cells and was not due to lipopolysaccharide (LPS) contamination. TSHR-CRPs were mitogenic for LPS-non-responsive spleen cells obtained from C3H/Hej mice, and polymyxin B did not inhibit the mitogenic activity of the TSHR-CRPs. TSHR-CRPs also induced high levels of IL-6 production in B cells and induced production and secretion of significant levels of IgG and IgM. Finally, culture supernatants from TSHR-CRP-stimulated spleen cells were shown by Western blot analysis to contain antibodies that recognized the ETSHR. These results identify for the first time two envelope proteins of Yersinia that have mitogenic activity and therefore could represent important proteins involved in the pathogenesis of Yersinia infections. Because these mitogenic proteins also contain epitopes crossreactive with the TSHR, they are potentially important for advancing our understanding of the role molecular mimicry plays in the induction of autoimmunity to the TSHR.",
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AU - Kaur, Indreshpal

AU - Niesel, David W.

AU - Seetharamaiah, Gattadahalli

AU - Peterson, Johnny W.

AU - Justement, Louis B.

AU - Prabhakar, Bellur S.

AU - Klimpel, Gary R.

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