Evaluation of T cell stimulation by thyrotropin-receptor epitopes in Graves’ disease
In Graves’ disease (GD) immunized T cells reactive to TSH-receptor epitopes contribute to pathogenesis through B cell help, and cytotoxicity. We evaluated T cell responses to synthetic TSH-receptor epitopes in hyperthyroid patients with GD prior to therapy, at 6–8 weeks after radioactive iodine (RAI...
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| Published in | Journal of endocrinological investigation Vol. 32; no. 1; pp. 52 - 56 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Cham
Springer International Publishing
01.01.2009
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0391-4097 1720-8386 1720-8386 |
| DOI | 10.1007/BF03345679 |
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| Abstract | In Graves’ disease (GD) immunized T cells reactive to TSH-receptor epitopes contribute to pathogenesis through B cell help, and cytotoxicity. We evaluated T cell responses to synthetic TSH-receptor epitopes in hyperthyroid patients with GD prior to therapy, at 6–8 weeks after radioactive iodine (RAI) administration, or 6–8 months later when euthyroid, and in control subjects. All T cell responses were relatively low as generally found in human autoimmune diseases. Responses in hyperthyroid GD patients were significantly greater than among controls, were augmented 6–8 weeks after RAI treatment, were still present after patients became euthyroid, and did not differ between DR3+ and non-DR3+ patients. Patient’s T cells reacted to multiple different epitopes, and reactivity differed depending on the course of the disease and treatment. While certain epitopes most commonly cause T cell reactivity, we did not find evidence for a single or few “dominant” epitopes. |
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| AbstractList | In Graves' disease (GD) immunized T cells reactive to TSH-receptor epitopes contribute to pathogenesis through B cell help, and cytotoxicity. We evaluated T cell responses to synthetic TSH-receptor epitopes in hyperthyroid patients with GD prior to therapy, at 6-8 weeks after radioactive iodine (RAI) administration, or 6-8 months later when euthyroid, and in control subjects. All T cell responses were relatively low as generally found in human autoimmune diseases. Responses in hyperthyroid GD patients were significantly greater than among controls, were augmented 6-8 weeks after RAI treatment, were still present after patients became euthyroid, and did not differ between DR3+ and non-DR3+ patients. Patient's T cells reacted to multiple different epitopes, and reactivity differed depending on the course of the disease and treatment.While certain epitopes most commonly cause T cell reactivity, we did not find evidence for a single or few "dominant" epitopes. In Graves' disease (GD) immunized T cells reactive to TSH-receptor epitopes contribute to pathogenesis through B cell help, and cytotoxicity. We evaluated T cell responses to synthetic TSH-receptor epitopes in hyperthyroid patients with GD prior to therapy, at 6-8 weeks after radioactive iodine (RAI) administration, or 6-8 months later when euthyroid, and in control subjects. All T cell responses were relatively low as generally found in human autoimmune diseases. Responses in hyperthyroid GD patients were significantly greater than among controls, were augmented 6-8 weeks after RAI treatment, were still present after patients became euthyroid, and did not differ between DR3+ and non-DR3+ patients. Patient's T cells reacted to multiple different epitopes, and reactivity differed depending on the course of the disease and treatment.While certain epitopes most commonly cause T cell reactivity, we did not find evidence for a single or few "dominant" epitopes.In Graves' disease (GD) immunized T cells reactive to TSH-receptor epitopes contribute to pathogenesis through B cell help, and cytotoxicity. We evaluated T cell responses to synthetic TSH-receptor epitopes in hyperthyroid patients with GD prior to therapy, at 6-8 weeks after radioactive iodine (RAI) administration, or 6-8 months later when euthyroid, and in control subjects. All T cell responses were relatively low as generally found in human autoimmune diseases. Responses in hyperthyroid GD patients were significantly greater than among controls, were augmented 6-8 weeks after RAI treatment, were still present after patients became euthyroid, and did not differ between DR3+ and non-DR3+ patients. Patient's T cells reacted to multiple different epitopes, and reactivity differed depending on the course of the disease and treatment.While certain epitopes most commonly cause T cell reactivity, we did not find evidence for a single or few "dominant" epitopes. |
| Author | De Groot, L. J. Pan, D. Gopalakrishnan, G. Hennessey, J. V. Shin, Y. Ha |
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| Keywords | autoimmune thyroid disease epitopes T cells Graves’ disease TSH-receptor |
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| References | PichurinPPhamNDavidCSRapoportBMcLachlanSMHLADR3 transgenic mice immunized with adenovirus encoding the thyrotropin receptor: T cell epitopes and functional analysis of the CD40 Graves’ polymorphismThyroid200616122171:CAS:528:DC%2BD2sXltFWr1719943210.1089/thy.2006.16.1221 GoodellVdela RosaCSlotaMMacLeodBDisisMLSensitivity and specificity of tritiated thymidine incorporation and ELISPOT assays in identifying antigen specific T cell immune responsesBMC Immunol200782120345951785066610.1186/1471-2172-8-21 RubioIGSilvaMNKnobelMPeripheral blood levels of thyroglobulin mRNA and serum thyroglobulin concentrations after radioiodine ablation of multinodular goiter with or without pre-treatment with recombinant human thyrotropinJ Endocrinol Invest200730535401:CAS:528:DC%2BD2sXht1yktrzI1784883410.1007/BF03346345 HidakaYGuimaraesVSolimanMProduction of thyroid-stimulating antibodies in mice by immunization with T-cell epitopes of human thyrotropin receptorEndocrinology1995136164271:CAS:528:DyaK2MXks1CisLo%3D7534706 SolimanMKaplanEStrausFGraves’ disease in severe combined immunodeficient miceJ Clin Endocrinol Metab1995802848551:CAS:528:DyaK2MXoslCnsrs%3D7559863 DeGroot LJ. Graves’ Disease; Chapter 10. Endocrine Education, Inc. www.thyroidmanager.org. Accessed October 10, 2007. FisfalenMEPalmerEMVan SeventerGAThyrotropin-receptor and thyroid peroxidase-specific T-cell clones and their cytokine profile in autoimmune thyroid diseaseJ Clin Endocrinol Metab1997823655631:CAS:528:DyaK2sXnt1Clsr0%3D9360522 SolimanMKaplanEGuimaraesVYanagawaTDeGrootLJT-cell recognition of residue 158–176 in thyrotropin receptor confers risk for development of thyroid autoimmunity in SIblings in a family with Graves’ diseaseThyroid19966545511:STN:280:DyaK2s7lsVCksg%3D%3D900118810.1089/thy.1996.6.545 SolimanMKaplanEYanagawaTHidakaYFisfalenMEDeGrootLJT-cells recognize multiple epitopes in the human thyrotropin receptor extra-cellular domainJ Clin Endocrinol Metab199580905141:CAS:528:DyaK2MXktlOntb0%3D7533773 TanJTSurhCDT cell memoryCurr Top Microbiol Immunol2006311851151:CAS:528:DC%2BD28Xht1WrsbbK17048706 EisenbarthGSUpdate in type 1 diabetesJ Clin Endocrinol Metab200792240371:CAS:528:DC%2BD2sXotVymu70%3D1761663410.1210/jc.2007-0339 FenziGHashizumeKRoudebushCPDeGrootLJChanges in thyroid-stimulating immunoglobulins during antithyroid therapyJ Clin Endocrinol Metab19794857261:STN:280:DyaE1M7ltFeksw%3D%3D58187510.1210/jcem-48-4-572 KamphuisSHrafnkelsdottirKKleinMRNovel self-epitopes derived from aggrecan, fibrillin, and matrix metalloproteinase-3 drive distinct autoreactive T-cell responses in juvenile idiopathic arthritis and in healthArthritis Res Ther20068R17817945231712937810.1186/ar2088 SolimanMKaplanEAbdel-LatifAScherbergNDeGrootLJDoesthyroidectomy, radioactive iodine therapy, orantithyroid drug treatment alter reactivity of patients’ T cells to epitopes of thyrotropin receptor in autoimmune thyroid diseases?J Clin endocrinol Metab1995802312211:CAS:528:DyaK2MXnsVCjsbc%3D754311210.1210/jcem.80.8.7543112 TandonNFreemanMAWeetmanAPT-cell responses to synthetic TSH receptor peptides in Graves’ diseaseClin Exp Immunol199289468731:CAS:528:DyaK3sXnvFWgug%3D%3D1554462151626110.1111/j.1365-2249.1992.tb06982.x DeGrootLJBenjasuratwongYEvaluation of thyroid ablative therapy for ophthalmopathy of Graves’ diseaseOrbit1996151879610.3109/01676839609150236 YouSLeforbanBGarciaCBachJFBluestoneJAChatenoudLAdaptive TGF-beta-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatmentProc Natl Acad Sci U S A20071046335401:CAS:528:DC%2BD2sXks1aqsrw%3D18510301738938210.1073/pnas.0701171104 SeddikiNSantner-NananBMartinsonJExpression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cellsJ Exp Med200620316937001:CAS:528:DC%2BD28XntVCgs7w%3D21183331681867610.1084/jem.20060468 WeetmanAPDeGrootLJJamesonJLAutoimmune thyroid diseaseEndocrinology20055thWB SaundersPhiladelphia197994 InabaHMartinWDe GrootASQinSDe GrootLJThyrotropin receptor epitopes and their relation to histocompatibility leukocyte antigen-DR molecules in Graves’ diseaseJ Clin Endocrinol Metab2006912286941:CAS:528:DC%2BD28XlvVCgtr0%3D1659560210.1210/jc.2005-2537 MartinANakashimaMZhouAAronsonDWernerAJDaviesTFDetection of major T-cell epitopes on human thyroid stimulating hormone receptor by overriding immune heterogeneity in patients with Graves’ diseaseJ Clin Endocrinol Metab199782336161:CAS:528:DyaK2sXmslOhsLk%3D9329369 GuimaraesVQuintansJFisfalenM-ESuppression of development of experimental autoimmune thyroiditis by oral administration of thyroglobulinEndocrinology1995136335391:CAS:528:DyaK2MXntFKntr4%3D7543043 ReijonenHNovakEJKochikSDetection of GAD65-specific T-cells by major histocompatibility complex class II tetramers in type 1 diabetic patients and at-risk subjectsDiabetes2002511375821:CAS:528:DC%2BD38XjtlGmt70%3D1197863310.2337/diabetes.51.5.1375 A Martin (BF03345679_CR9) 1997; 82 GS Eisenbarth (BF03345679_CR3) 2007; 92 Y Hidaka (BF03345679_CR8) 1995; 136 N Seddiki (BF03345679_CR21) 2006; 203 P Pichurin (BF03345679_CR11) 2006; 16 M Soliman (BF03345679_CR13) 1995; 80 V Guimaraes (BF03345679_CR23) 1995; 136 AP Weetman (BF03345679_CR2) 2005 H Inaba (BF03345679_CR12) 2006; 91 M Soliman (BF03345679_CR4) 1995; 80 JT Tan (BF03345679_CR18) 2006; 311 ME Fisfalen (BF03345679_CR7) 1997; 82 N Tandon (BF03345679_CR10) 1992; 89 G Fenzi (BF03345679_CR16) 1979; 48 LJ DeGroot (BF03345679_CR19) 1996; 15 BF03345679_CR1 H Reijonen (BF03345679_CR22) 2002; 51 IG Rubio (BF03345679_CR17) 2007; 30 V Goodell (BF03345679_CR20) 2007; 8 M Soliman (BF03345679_CR5) 1995; 80 S Kamphuis (BF03345679_CR14) 2006; 8 S You (BF03345679_CR15) 2007; 104 M Soliman (BF03345679_CR6) 1996; 6 17048706 - Curr Top Microbiol Immunol. 2006;311:85-115 17199432 - Thyroid. 2006 Dec;16(12):1221-7 17848834 - J Endocrinol Invest. 2007 Jul-Aug;30(7):535-40 16595602 - J Clin Endocrinol Metab. 2006 Jun;91(6):2286-94 17616634 - J Clin Endocrinol Metab. 2007 Jul;92(7):2403-7 17850666 - BMC Immunol. 2007 Sep 12;8:21 7559863 - J Clin Endocrinol Metab. 1995 Oct;80(10):2848-55 9001188 - Thyroid. 1996 Dec;6(6):545-51 9360522 - J Clin Endocrinol Metab. 1997 Nov;82(11):3655-63 17389382 - Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6335-40 7543112 - J Clin Endocrinol Metab. 1995 Aug;80(8):2312-21 16818676 - J Exp Med. 2006 Jul 10;203(7):1693-700 7534706 - Endocrinology. 1995 Apr;136(4):1642-7 11978633 - Diabetes. 2002 May;51(5):1375-82 17129378 - Arthritis Res Ther. 2006;8(6):R178 1516261 - Clin Exp Immunol. 1992 Sep;89(3):468-73 7543043 - Endocrinology. 1995 Aug;136(8):3353-9 7533773 - J Clin Endocrinol Metab. 1995 Mar;80(3):905-14 581875 - J Clin Endocrinol Metab. 1979 Apr;48(4):572-6 9329369 - J Clin Endocrinol Metab. 1997 Oct;82(10):3361-6 |
| References_xml | – reference: MartinANakashimaMZhouAAronsonDWernerAJDaviesTFDetection of major T-cell epitopes on human thyroid stimulating hormone receptor by overriding immune heterogeneity in patients with Graves’ diseaseJ Clin Endocrinol Metab199782336161:CAS:528:DyaK2sXmslOhsLk%3D9329369 – reference: RubioIGSilvaMNKnobelMPeripheral blood levels of thyroglobulin mRNA and serum thyroglobulin concentrations after radioiodine ablation of multinodular goiter with or without pre-treatment with recombinant human thyrotropinJ Endocrinol Invest200730535401:CAS:528:DC%2BD2sXht1yktrzI1784883410.1007/BF03346345 – reference: PichurinPPhamNDavidCSRapoportBMcLachlanSMHLADR3 transgenic mice immunized with adenovirus encoding the thyrotropin receptor: T cell epitopes and functional analysis of the CD40 Graves’ polymorphismThyroid200616122171:CAS:528:DC%2BD2sXltFWr1719943210.1089/thy.2006.16.1221 – reference: DeGroot LJ. Graves’ Disease; Chapter 10. Endocrine Education, Inc. www.thyroidmanager.org. Accessed October 10, 2007. – reference: SolimanMKaplanEStrausFGraves’ disease in severe combined immunodeficient miceJ Clin Endocrinol Metab1995802848551:CAS:528:DyaK2MXoslCnsrs%3D7559863 – reference: YouSLeforbanBGarciaCBachJFBluestoneJAChatenoudLAdaptive TGF-beta-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatmentProc Natl Acad Sci U S A20071046335401:CAS:528:DC%2BD2sXks1aqsrw%3D18510301738938210.1073/pnas.0701171104 – reference: SolimanMKaplanEGuimaraesVYanagawaTDeGrootLJT-cell recognition of residue 158–176 in thyrotropin receptor confers risk for development of thyroid autoimmunity in SIblings in a family with Graves’ diseaseThyroid19966545511:STN:280:DyaK2s7lsVCksg%3D%3D900118810.1089/thy.1996.6.545 – reference: FenziGHashizumeKRoudebushCPDeGrootLJChanges in thyroid-stimulating immunoglobulins during antithyroid therapyJ Clin Endocrinol Metab19794857261:STN:280:DyaE1M7ltFeksw%3D%3D58187510.1210/jcem-48-4-572 – reference: HidakaYGuimaraesVSolimanMProduction of thyroid-stimulating antibodies in mice by immunization with T-cell epitopes of human thyrotropin receptorEndocrinology1995136164271:CAS:528:DyaK2MXks1CisLo%3D7534706 – reference: TandonNFreemanMAWeetmanAPT-cell responses to synthetic TSH receptor peptides in Graves’ diseaseClin Exp Immunol199289468731:CAS:528:DyaK3sXnvFWgug%3D%3D1554462151626110.1111/j.1365-2249.1992.tb06982.x – reference: KamphuisSHrafnkelsdottirKKleinMRNovel self-epitopes derived from aggrecan, fibrillin, and matrix metalloproteinase-3 drive distinct autoreactive T-cell responses in juvenile idiopathic arthritis and in healthArthritis Res Ther20068R17817945231712937810.1186/ar2088 – reference: WeetmanAPDeGrootLJJamesonJLAutoimmune thyroid diseaseEndocrinology20055thWB SaundersPhiladelphia197994 – reference: SolimanMKaplanEAbdel-LatifAScherbergNDeGrootLJDoesthyroidectomy, radioactive iodine therapy, orantithyroid drug treatment alter reactivity of patients’ T cells to epitopes of thyrotropin receptor in autoimmune thyroid diseases?J Clin endocrinol Metab1995802312211:CAS:528:DyaK2MXnsVCjsbc%3D754311210.1210/jcem.80.8.7543112 – reference: SolimanMKaplanEYanagawaTHidakaYFisfalenMEDeGrootLJT-cells recognize multiple epitopes in the human thyrotropin receptor extra-cellular domainJ Clin Endocrinol Metab199580905141:CAS:528:DyaK2MXktlOntb0%3D7533773 – reference: ReijonenHNovakEJKochikSDetection of GAD65-specific T-cells by major histocompatibility complex class II tetramers in type 1 diabetic patients and at-risk subjectsDiabetes2002511375821:CAS:528:DC%2BD38XjtlGmt70%3D1197863310.2337/diabetes.51.5.1375 – reference: GoodellVdela RosaCSlotaMMacLeodBDisisMLSensitivity and specificity of tritiated thymidine incorporation and ELISPOT assays in identifying antigen specific T cell immune responsesBMC Immunol200782120345951785066610.1186/1471-2172-8-21 – reference: GuimaraesVQuintansJFisfalenM-ESuppression of development of experimental autoimmune thyroiditis by oral administration of thyroglobulinEndocrinology1995136335391:CAS:528:DyaK2MXntFKntr4%3D7543043 – reference: TanJTSurhCDT cell memoryCurr Top Microbiol Immunol2006311851151:CAS:528:DC%2BD28Xht1WrsbbK17048706 – reference: DeGrootLJBenjasuratwongYEvaluation of thyroid ablative therapy for ophthalmopathy of Graves’ diseaseOrbit1996151879610.3109/01676839609150236 – reference: EisenbarthGSUpdate in type 1 diabetesJ Clin Endocrinol Metab200792240371:CAS:528:DC%2BD2sXotVymu70%3D1761663410.1210/jc.2007-0339 – reference: FisfalenMEPalmerEMVan SeventerGAThyrotropin-receptor and thyroid peroxidase-specific T-cell clones and their cytokine profile in autoimmune thyroid diseaseJ Clin Endocrinol Metab1997823655631:CAS:528:DyaK2sXnt1Clsr0%3D9360522 – reference: SeddikiNSantner-NananBMartinsonJExpression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cellsJ Exp Med200620316937001:CAS:528:DC%2BD28XntVCgs7w%3D21183331681867610.1084/jem.20060468 – reference: InabaHMartinWDe GrootASQinSDe GrootLJThyrotropin receptor epitopes and their relation to histocompatibility leukocyte antigen-DR molecules in Graves’ diseaseJ Clin Endocrinol Metab2006912286941:CAS:528:DC%2BD28XlvVCgtr0%3D1659560210.1210/jc.2005-2537 – volume: 104 start-page: 6335 year: 2007 ident: BF03345679_CR15 publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0701171104 – volume: 82 start-page: 3655 year: 1997 ident: BF03345679_CR7 publication-title: J Clin Endocrinol Metab – volume: 6 start-page: 545 year: 1996 ident: BF03345679_CR6 publication-title: Thyroid doi: 10.1089/thy.1996.6.545 – volume: 8 start-page: R178 year: 2006 ident: BF03345679_CR14 publication-title: Arthritis Res Ther doi: 10.1186/ar2088 – volume: 136 start-page: 1642 year: 1995 ident: BF03345679_CR8 publication-title: Endocrinology doi: 10.1210/endo.136.4.7534706 – volume: 92 start-page: 2403 year: 2007 ident: BF03345679_CR3 publication-title: J Clin Endocrinol Metab doi: 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| Snippet | In Graves’ disease (GD) immunized T cells reactive to TSH-receptor epitopes contribute to pathogenesis through B cell help, and cytotoxicity. We evaluated T... In Graves' disease (GD) immunized T cells reactive to TSH-receptor epitopes contribute to pathogenesis through B cell help, and cytotoxicity. We evaluated T... |
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| SubjectTerms | Endocrinology Epitopes - immunology Graves Disease - immunology Graves Disease - radiotherapy Humans Iodine Radioisotopes - therapeutic use Medicine Medicine & Public Health Metabolic Diseases Original Articles Receptors, Thyrotropin - immunology Reproducibility of Results T-Lymphocytes - immunology |
| Title | Evaluation of T cell stimulation by thyrotropin-receptor epitopes in Graves’ disease |
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