Hashimoto’s Thyroiditis with Heterogeneous Antithyrotropin Receptor Antibodies: Unique Epitopes May Contribute to the Regulation of Thyroid Function by the Antibodies1
| Autor: | Kazuwa Nakao, Kazuo Tahara, Misa Saijo, Takashi Akamizu, Hitomi Hiratani, Leonard D. Kohn |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
endocrine system
medicine.medical_specialty Goiter endocrine system diseases Endocrinology Diabetes and Metabolism Clinical Biochemistry Biochemistry Thyroiditis Epitope Endocrinology Internal medicine medicine business.industry Biochemistry (medical) Thyroid medicine.disease eye diseases Anti-thyroid autoantibodies medicine.anatomical_structure Immunology Thyroid Stimulating Immunoglobulin Thyroid function Myxedema business hormones hormone substitutes and hormone antagonists |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 85:2116-2121 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.85.6.6639 |
| Popis: | Blocking-type TSH-binding inhibitor Igs (TBIIs) are known to cause hypothyroidism and an atrophic thyroid gland in patients with primary myxedema. They can block the activity of thyroid-stimulating antibodies (TSAbs) in Graves' patients as well as the activity of TSH. The majority of the epitopes for these blocking-type TBIIs have been, and are shown herein, to be present on the C-terminal region of the extracellular domain of the human TSH receptor (TSHR), whereas those for Graves' TSAbs are on the N-terminus. We report on a patient with Hashimoto's thyroiditis who suffered from mild hypothyroidism and a moderately sized goiter. Her serum had a potent blocking-type TBII and a weak TSAb in human and porcine TSHR systems. Using human TSHR/lutropin-CG receptor chimeras, we determined that the functional epitope of her blocking-type TBII was uniquely present on the N-terminal, rather than the C-terminal, region of the extracellular domain of the TSHR, unlike the case for blocking-type TBIIs in primary myxedema patients. The epitope of her TSAb was also unusual. Although the functional epitopes of most TSAbs are known to involve the N-terminal region of the receptor, her TSAb epitope did not seem to be present solely on the N- or C-terminus of the extracellular domain of the receptor. Blocking-type TBIIs from patients with primary myxedema blocked her TSAb activity as well as stimulation by TSH; her blocking-type TBII was able to only partially block her TSAb. In contrast, her blocking-type TBII almost completely blocked TSAbs from Graves' patients. Thus, we suggest that the unique epitopes of this patient's heterogeneous population of TSH receptor antibodies, at least in part, contribute to regulation of her thyroid function. |
| Databáze: | OpenAIRE |
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