Immunization of Mice with Yersinia enterocolitica Leads to the Induction of Antithyrotropin Receptor Antibodies

Guoyang Luo, Ji Lao Fan, Gattadahalli S. Seetharamaiah, Rajesh K. Desai, John S. Dallas, Neelam Wagle, Richard Doan, David Niesel, Gary R. Klimpel, Bellur S. Prabhakar

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

It is well established that autoimmune Graves' disease, which is characterized by hyperthyroidism, is mediated by autoantibodies to the thyrotropin receptor (TSHr). Although what initially triggers this autoantibody response is not known, a number of studies have suggested that Yersinia enterocolitica, an enterobacteria, could initiate the immune response against the TSHr. In this study, we produced antibodies against purified extracellular domain of human TSHr (ETSHr) and showed that anti-ETSHr antibodies reacted with envelope preparations from Y. enterocolitica. This reactivity was specifically blocked by preincubating sera with purified ETSHr. Moreover, antibodies reactive with ETSHr were induced by immunizing mice with Y. enterocolitica but not with Shigella flexneri SA100, Salmonella typhimurium TML, and Listeria monocytogenes. Anti-Y. enterocolitica antisera specifically reacted with the ETSHr protein and the reactivity could be blocked both by ETSHr and Y. enterocolitica envelope proteins. Our studies provide the first direct evidence that immunization with Y. enterocolitica can lead to the production of antibodies capable of reacting with TSHr and might provide the initial stimulus necessary for breakdown of self-tolerance to TSHr, eventually leading to the development of autoimmunity to TSHr.

Original languageEnglish (US)
Pages (from-to)922-928
Number of pages7
JournalJournal of Immunology
Volume151
Issue number2
StatePublished - Jul 15 1993

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Yersinia enterocolitica
Immunization
Antibodies
Autoantibodies
Shigella flexneri
Self Tolerance
Thyrotropin Receptors
Graves Disease
Listeria monocytogenes
Enterobacteriaceae
Hyperthyroidism
Salmonella typhimurium
Autoimmunity
Autoimmune Diseases
Antibody Formation
Immune Sera
Anti-Idiotypic Antibodies
Proteins
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Luo, G., Fan, J. L., Seetharamaiah, G. S., Desai, R. K., Dallas, J. S., Wagle, N., ... Prabhakar, B. S. (1993). Immunization of Mice with Yersinia enterocolitica Leads to the Induction of Antithyrotropin Receptor Antibodies. Journal of Immunology, 151(2), 922-928.

Immunization of Mice with Yersinia enterocolitica Leads to the Induction of Antithyrotropin Receptor Antibodies. / Luo, Guoyang; Fan, Ji Lao; Seetharamaiah, Gattadahalli S.; Desai, Rajesh K.; Dallas, John S.; Wagle, Neelam; Doan, Richard; Niesel, David; Klimpel, Gary R.; Prabhakar, Bellur S.

In: Journal of Immunology, Vol. 151, No. 2, 15.07.1993, p. 922-928.

Research output: Contribution to journalArticle

Luo, G, Fan, JL, Seetharamaiah, GS, Desai, RK, Dallas, JS, Wagle, N, Doan, R, Niesel, D, Klimpel, GR & Prabhakar, BS 1993, 'Immunization of Mice with Yersinia enterocolitica Leads to the Induction of Antithyrotropin Receptor Antibodies', Journal of Immunology, vol. 151, no. 2, pp. 922-928.
Luo G, Fan JL, Seetharamaiah GS, Desai RK, Dallas JS, Wagle N et al. Immunization of Mice with Yersinia enterocolitica Leads to the Induction of Antithyrotropin Receptor Antibodies. Journal of Immunology. 1993 Jul 15;151(2):922-928.
Luo, Guoyang ; Fan, Ji Lao ; Seetharamaiah, Gattadahalli S. ; Desai, Rajesh K. ; Dallas, John S. ; Wagle, Neelam ; Doan, Richard ; Niesel, David ; Klimpel, Gary R. ; Prabhakar, Bellur S. / Immunization of Mice with Yersinia enterocolitica Leads to the Induction of Antithyrotropin Receptor Antibodies. In: Journal of Immunology. 1993 ; Vol. 151, No. 2. pp. 922-928.
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abstract = "It is well established that autoimmune Graves' disease, which is characterized by hyperthyroidism, is mediated by autoantibodies to the thyrotropin receptor (TSHr). Although what initially triggers this autoantibody response is not known, a number of studies have suggested that Yersinia enterocolitica, an enterobacteria, could initiate the immune response against the TSHr. In this study, we produced antibodies against purified extracellular domain of human TSHr (ETSHr) and showed that anti-ETSHr antibodies reacted with envelope preparations from Y. enterocolitica. This reactivity was specifically blocked by preincubating sera with purified ETSHr. Moreover, antibodies reactive with ETSHr were induced by immunizing mice with Y. enterocolitica but not with Shigella flexneri SA100, Salmonella typhimurium TML, and Listeria monocytogenes. Anti-Y. enterocolitica antisera specifically reacted with the ETSHr protein and the reactivity could be blocked both by ETSHr and Y. enterocolitica envelope proteins. Our studies provide the first direct evidence that immunization with Y. enterocolitica can lead to the production of antibodies capable of reacting with TSHr and might provide the initial stimulus necessary for breakdown of self-tolerance to TSHr, eventually leading to the development of autoimmunity to TSHr.",
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