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

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 μ...

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Autores principales: Furmaniak, Jadwiga, Sanders, Jane, Young, Stuart, Kabelis, Katarzyna, Sanders, Paul, Evans, Michele, Clark, Jill, Wilmot, Jane, Rees Smith, Bernard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389019/
https://www.ncbi.nlm.nih.gov/pubmed/26000124
http://dx.doi.org/10.1007/s13317-011-0025-9
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author Furmaniak, Jadwiga
Sanders, Jane
Young, Stuart
Kabelis, Katarzyna
Sanders, Paul
Evans, Michele
Clark, Jill
Wilmot, Jane
Rees Smith, Bernard
author_facet Furmaniak, Jadwiga
Sanders, Jane
Young, Stuart
Kabelis, Katarzyna
Sanders, Paul
Evans, Michele
Clark, Jill
Wilmot, Jane
Rees Smith, Bernard
author_sort Furmaniak, Jadwiga
collection PubMed
description 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.
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spelling pubmed-43890192015-05-21 In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70) Furmaniak, Jadwiga Sanders, Jane Young, Stuart Kabelis, Katarzyna Sanders, Paul Evans, Michele Clark, Jill Wilmot, Jane Rees Smith, Bernard Auto Immun Highlights Original Article 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. Springer International Publishing 2011-09-14 /pmc/articles/PMC4389019/ /pubmed/26000124 http://dx.doi.org/10.1007/s13317-011-0025-9 Text en © Springer-Verlag 2011
spellingShingle Original Article
Furmaniak, Jadwiga
Sanders, Jane
Young, Stuart
Kabelis, Katarzyna
Sanders, Paul
Evans, Michele
Clark, Jill
Wilmot, Jane
Rees Smith, Bernard
In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70)
title In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70)
title_full In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70)
title_fullStr In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70)
title_full_unstemmed In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70)
title_short In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70)
title_sort in vivo effects of a human thyroid-stimulating monoclonal autoantibody (m22) and a human thyroid-blocking autoantibody (k1-70)
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389019/
https://www.ncbi.nlm.nih.gov/pubmed/26000124
http://dx.doi.org/10.1007/s13317-011-0025-9
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