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

Academic Article

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. © 2011 Springer-Verlag.
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    Author List

  • Furmaniak J; Sanders J; Young S; Kabelis K; Sanders P; Evans M; Clark J; Wilmot J; Smith BR
  • Start Page

  • 19
  • End Page

  • 25
  • Volume

  • 3
  • Issue

  • 1