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Hashimoto’s Thyroiditis with Heterogeneous Antithyrotropin Receptor Antibodies: Unique Epitopes May Contribute to the Regulation of Thyroid Function by the Antibodies1
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 fo...
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Published in: | The journal of clinical endocrinology and metabolism 2000-06, Vol.85 (6), p.2116-2121 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.85.6.6639 |