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Article: Epitope mapping of TSH receptor-blocking antibodies in Graves' disease that appear during pregnancy

TitleEpitope mapping of TSH receptor-blocking antibodies in Graves' disease that appear during pregnancy
Authors
Issue Date2001
PublisherThe Endocrine Society. The Journal's web site is located at http://jcem.endojournals.org
Citation
Journal Of Clinical Endocrinology And Metabolism, 2001, v. 86 n. 8, p. 3647-3653 How to Cite?
AbstractSpontaneous remission of Graves' disease during pregnancy is thought to be due to a reduction of thyroid-stimulating antibody activity. We suspected, however, that a broader change in TSH receptor antibody characteristics might play an important role in modulating disease activity during pregnancy. We measured TSH binding inhibitory Ig, thyroid-stimulating antibody, and thyroid stimulating-blocking antibody activities in 13 pregnant Graves' disease patients at first, second, and third trimesters and 4 months postpartum. To measure and epitope-map thyroid-stimulating antibody and thyroid stimulating-blocking antibody activities, we used CHO cells transfected with wild-type human TSH receptor or with several TSH receptor-LH/hCG receptor chimeras: Mc1+2, Mc2, and Mc4. These chimeric cells have their respective TSH receptor residues 9-165, 90-165, and 261-370 substituted with equivalent residues of the LH/hCG receptor. Overall thyroid-stimulating antibody decreased, whereas thyroid stimulating-blocking antibody increased progressively during pregnancy. TSH binding inhibitory Ig fluctuated in individual patients, but overall the activities remained statistically unchanged. Thyroid stimulating-blocking antibody appeared in subjects who were either negative for thyroid-stimulating antibody or whose thyroid-stimulating antibody activity increased or decreased during pregnancy. Epitope mapping showed that the thyroid-stimulating antibodies were mainly directed against residues 9-165 of the N-terminus of the TSH receptor extracellular domain. All thyroid stimulating-blocking antibodies had blocking activities against residues 261-370 of the C-terminus of the ectodomain. However, the majority of the thyroid stimulating-blocking antibodies had a hybrid conformational epitope directed against N-terminal residues 9-89 or 90-165 as well. Despite a change in the activity level, we did not observe any change in the epitope of either the stimulatory or blocking Abs as pregnancy advanced. In conclusion, a change in the specificity of TSH receptor antibody from stimulatory to blocking activity was observed during pregnancy, and the appearance of thyroid stimulating-blocking antibody may contribute to the remission of Graves' disease during pregnancy.
Persistent Identifierhttp://hdl.handle.net/10722/162475
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.940
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKung, AWCen_US
dc.contributor.authorLau, KSen_US
dc.contributor.authorKohn, LDen_US
dc.date.accessioned2012-09-05T05:20:18Z-
dc.date.available2012-09-05T05:20:18Z-
dc.date.issued2001en_US
dc.identifier.citationJournal Of Clinical Endocrinology And Metabolism, 2001, v. 86 n. 8, p. 3647-3653en_US
dc.identifier.issn0021-972Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/162475-
dc.description.abstractSpontaneous remission of Graves' disease during pregnancy is thought to be due to a reduction of thyroid-stimulating antibody activity. We suspected, however, that a broader change in TSH receptor antibody characteristics might play an important role in modulating disease activity during pregnancy. We measured TSH binding inhibitory Ig, thyroid-stimulating antibody, and thyroid stimulating-blocking antibody activities in 13 pregnant Graves' disease patients at first, second, and third trimesters and 4 months postpartum. To measure and epitope-map thyroid-stimulating antibody and thyroid stimulating-blocking antibody activities, we used CHO cells transfected with wild-type human TSH receptor or with several TSH receptor-LH/hCG receptor chimeras: Mc1+2, Mc2, and Mc4. These chimeric cells have their respective TSH receptor residues 9-165, 90-165, and 261-370 substituted with equivalent residues of the LH/hCG receptor. Overall thyroid-stimulating antibody decreased, whereas thyroid stimulating-blocking antibody increased progressively during pregnancy. TSH binding inhibitory Ig fluctuated in individual patients, but overall the activities remained statistically unchanged. Thyroid stimulating-blocking antibody appeared in subjects who were either negative for thyroid-stimulating antibody or whose thyroid-stimulating antibody activity increased or decreased during pregnancy. Epitope mapping showed that the thyroid-stimulating antibodies were mainly directed against residues 9-165 of the N-terminus of the TSH receptor extracellular domain. All thyroid stimulating-blocking antibodies had blocking activities against residues 261-370 of the C-terminus of the ectodomain. However, the majority of the thyroid stimulating-blocking antibodies had a hybrid conformational epitope directed against N-terminal residues 9-89 or 90-165 as well. Despite a change in the activity level, we did not observe any change in the epitope of either the stimulatory or blocking Abs as pregnancy advanced. In conclusion, a change in the specificity of TSH receptor antibody from stimulatory to blocking activity was observed during pregnancy, and the appearance of thyroid stimulating-blocking antibody may contribute to the remission of Graves' disease during pregnancy.en_US
dc.languageengen_US
dc.publisherThe Endocrine Society. The Journal's web site is located at http://jcem.endojournals.orgen_US
dc.relation.ispartofJournal of Clinical Endocrinology and Metabolismen_US
dc.rightsJournal of Clinical Endocrinology and Metabolism. Copyright © The Endocrine Society.-
dc.subject.meshAdulten_US
dc.subject.meshAnalysis Of Varianceen_US
dc.subject.meshAntithyroid Agents - Therapeutic Useen_US
dc.subject.meshEpitopes - Analysisen_US
dc.subject.meshFemaleen_US
dc.subject.meshGraves Disease - Blood - Drug Therapy - Immunologyen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoglobulin G - Blooden_US
dc.subject.meshImmunoglobulins, Thyroid-Stimulating - Blooden_US
dc.subject.meshPostpartum Period - Blood - Immunologyen_US
dc.subject.meshPregnancyen_US
dc.subject.meshPregnancy Complications - Blood - Immunologyen_US
dc.subject.meshReceptors, Thyrotropin - Immunologyen_US
dc.subject.meshThyroid Function Testsen_US
dc.subject.meshThyrotropin - Blood - Immunologyen_US
dc.subject.meshThyroxine - Blooden_US
dc.subject.meshTime Factorsen_US
dc.subject.meshTriiodothyronine - Blooden_US
dc.titleEpitope mapping of TSH receptor-blocking antibodies in Graves' disease that appear during pregnancyen_US
dc.typeArticleen_US
dc.identifier.emailKung, AWC:awckung@hku.hken_US
dc.identifier.authorityKung, AWC=rp00368en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1210/jc.86.8.3647en_US
dc.identifier.pmid11502791-
dc.identifier.scopuseid_2-s2.0-0034886412en_US
dc.identifier.hkuros66569-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034886412&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume86en_US
dc.identifier.issue8en_US
dc.identifier.spage3647en_US
dc.identifier.epage3653en_US
dc.identifier.isiWOS:000170430200027-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridKung, AWC=7102322339en_US
dc.identifier.scopusauthoridLau, KS=35205833900en_US
dc.identifier.scopusauthoridKohn, LD=8887452100en_US

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