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

被引:45
作者
Furmaniak, Jadwiga [1 ]
Sanders, Jane [1 ]
Young, Stuart [1 ]
Kabelis, Katarzyna [1 ]
Sanders, Paul [1 ]
Evans, Michele [1 ]
Clark, Jill [1 ]
Wilmot, Jane [1 ]
Smith, Bernard Rees [1 ]
机构
[1] RSR Ltd, FIRS Labs, Parc Ty Glas, Cardiff CF14 5DU, S Glam, Wales
关键词
Thyroid; Graves' disease; TSH receptor; Thyroid-stimulating antibodies; Thyroid-blocking antibodies; Autoimmunity;
D O I
10.1007/s13317-011-0025-9
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 lg/animal), K1-70 IgG (10-200 lg/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.
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收藏
页码:19 / 25
页数:7
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