title: In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70).
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, CF14 5DU UK.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Furmaniak
authors.affiliation: FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, CF14 5DU UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Sanders
authors.affiliation: FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, CF14 5DU UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Young
authors.affiliation: FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, CF14 5DU UK.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kabelis
authors.affiliation: FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, CF14 5DU UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Sanders
authors.affiliation: FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, CF14 5DU UK.
authors.forename: Michele
authors.initials: M
authors.lastname: Evans
authors.affiliation: FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, CF14 5DU UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Clark
authors.affiliation: FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, CF14 5DU UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Wilmot
authors.affiliation: FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, CF14 5DU UK.
authors.forename: Bernard
authors.initials: B
authors.lastname: Rees Smith
keywords: Autoimmunity; Graves’ disease; TSH receptor; Thyroid; Thyroid-blocking antibodies; Thyroid-stimulating antibodies