In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70)

  • Auto Immun Highlights. 2011 Sep 14;3(1):19-25. doi: 10.1007/s13317-011-0025-9.
Jadwiga Furmaniak  1 ,  Jane Sanders  1 ,  Stuart Young  1 ,  Katarzyna Kabelis  1 ,  Paul Sanders  1 ,  Michele Evans  1 ,  Jill Clark  1 ,  Jane Wilmot  1 ,  Bernard Rees Smith  1
Affiliations
  • 1. FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, CF14 5DU UK.
PMID: 26000124 DOI: 10.1007/s13317-011-0025-9
Abstract

Purpose: To study in vivo effects of the human monoclonal TSH Receptor (TSHR) autoantibodies M22 (stimulating type) and K1-70 (blocking type) on thyroid hormone levels in rats.

Methods: Serum levels of total T4, free T4, M22 and K1-70 were measured following intramuscular injection of M22 IgG (2-4 μg/animal), K1-70 IgG (10-200 μg/animal) or both into rats. Thyroid pathology was assessed in M22-injected rats.

Results: Serum levels of total T4 and free T4 increased in a dose-dependent manner following injection of M22 IgG. Thyroid follicular cell hypertrophy was dependent on the dose of M22 IgG. K1-70 IgG caused a dose dependent decrease of total T4 and free T4 levels in rats receiving K1-70 only. The stimulating effects of M22 IgG on T4 levels in rats were completely inhibited by K1-70 IgG.

Conclusion: M22 is a potent stimulator of thyroid hormone secretion in vivo. In contrast, K1-70 inhibits thyroid hormone secretion in vivo. Furthermore, K1-70 has the ability to inhibit the stimulating activity of M22 in vivo and as such has potential as a new drug to block TSHR stimulation by autoantibodies in Graves' disease.

Keywords
Autoimmunity; Graves’ disease; TSH receptor; Thyroid; Thyroid-blocking antibodies; Thyroid-stimulating antibodies.
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