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Horm Metab Res 2009; 41(6): 448-455
DOI: 10.1055/s-0029-1220913
Review

© Georg Thieme Verlag KG Stuttgart · New York

TSH Receptor – Autoantibody Interactions

B. Rees Smith 1 , J. Sanders 1 , M. Evans 1 , T. Tagami 2 , J. Furmaniak 1
  • 1FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, UK
  • 2National Hospital Organization, Kyoto Medical Center, 1-1, Mukaihata-cho, Fukakusa Fushmi-ku, Kyoto, Japan
Further Information

Publication History

received 03.03.2009

accepted 22.04.2009

Publication Date:
20 May 2009 (online)

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Abstract

TSH receptor (TSHR) autoantibodies (TRAbs) activate the TSHR cyclic AMP cascade (stimulating TRAbs) or act as TSHR antagonist (blocking TRAbs), and both types inhibit TSH binding to the TSHR. Isolation of human monoclonal TSHR autoantibodies (stimulating M22 and blocking 5C9) has been a key milestone in studies of the TSHR and TSHR autoimmunity. Comparison of M22 and TSH interactions with the TSHR at the atomic level reveal that M22 heavy and light chains mimic TSH α and β chains, respectively, in the way they bind to the receptor, but the evolutionary forces which have caused this close molecular mimicry are as yet completely unknown. More recently two more human monoclonal antibodies to the TSHR (K1-18 with stimulating and K1-70 with blocking activities) have been isolated from a single blood sample collected from a patient with hypothyroidism who previously presented with hyperthyroidism. K1-18 and K1-70 were derived from different lymphocytes as shown by V region genes analysis. This provides, for the first time, clear proof that a patient can produce both blocking and stimulating TRAbs at the same time. Although it has been postulated that stimulating and blocking TRAbs bind to different regions on the TSHR, our studies showed that antibodies of both types bind well to the TSHR containing only N-terminal amino acids 22–260. Whether TRAbs make contact with other parts of the TSHR in order to produce their biological effects (stimulation or blocking) remains to be elucidated.

Key words

Graves’ disease - TSH - TSH receptor antibodies - autoimmunity

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Correspondence

Dr. B. Rees Smith

FIRS Laboratories

RSR Ltd

Parc Ty Glas

Llanishen

Cardiff CF14 5DU

UK

Phone: +44/29/2076 55 50

Fax: +44/29/2076 45 75

Email: firs@rsrltd.eclipse.co.uk