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Horm Metab Res 2015; 47(10): 727-734
DOI: 10.1055/s-0035-1559633
Review

Graves’ Disease Mechanisms: The Role of Stimulating, Blocking, and Cleavage Region TSH Receptor Antibodies

S. A. Morshed
1   Thyroid Research Unit, Icahn School of Medicine at Mount Sinai, James J. Peters VA Medical Center, New York, USA
,
T. F. Davies
1   Thyroid Research Unit, Icahn School of Medicine at Mount Sinai, James J. Peters VA Medical Center, New York, USA
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Abstract

The immunologic processes involved in Graves’ disease (GD) have one unique characteristic – the autoantibodies to the TSH receptor (TSHR) – which have both linear and conformational epitopes. Three types of TSHR antibodies (stimulating, blocking, and cleavage) with different functional capabilities have been described in GD patients, which induce different signaling effects varying from thyroid cell proliferation to thyroid cell death. The establishment of animal models of GD by TSHR antibody transfer or by immunization with TSHR antigen has confirmed its pathogenic role and, therefore, GD is the result of a breakdown in TSHR tolerance. Here we review some of the characteristics of TSHR antibodies with a special emphasis on new developments in our understanding of what were previously called “neutral” antibodies and which we now characterize as autoantibodies to the “cleavage” region of the TSHR ectodomain.

Key words

Graves’ disease - thyroid - TSH-receptor antibodies - TSH - signaling


Publication History

Received: 13 April 2015

Accepted: 10 July 2015

Article published online:
11 September 2015

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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