A Novel Monoclonal Antibody Degrades the Thyrotropin Receptor Autoantibodies in Graves' Disease.

Autor:	Wolf J; Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany., Alt S; Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany., Krämer I; Department of Pharmacy, Johannes Gutenberg University Medical Center, Mainz, Germany., Kahaly GJ; Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany. Electronic address: george.kahaly@unimedizin-mainz.de.
Jazyk:	angličtina
Zdroj:	Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists [Endocr Pract] 2023 Jul; Vol. 29 (7), pp. 553-559. Date of Electronic Publication: 2023 Apr 18.
DOI:	10.1016/j.eprac.2023.04.002
Abstrakt:	Objective: Autoantibodies against the thyrotropin receptor (TSH-R-Ab) are key mediators for the pathogenesis of Graves' disease (GD). TSH-R-Ab degradation was evaluated using several immunoassays within an exploratory, controlled trial in patients with GD receiving a monoclonal antibody (mAb) targeting the neonatal crystallizable fragment receptor (FcRn). Methods: Serial measurements of TSH-R-Ab serum levels were performed using 3 different binding and cell-based assays in patients with GD either on medication or on placebo. Results: In contrast to the placebo group, in which no changes were observed, a 12-week mAb therapy led to an early and significant decrease (>60%) in the serum TSH-R-Ab levels in patients with thyroidal and extrathyroidal GD, as unanimously shown in all 3 assays. These marked changes were noted already at week 7 post baseline (P <.0001 for the binding immunoassay and for the luciferase (readout) bioassay). The 3 TSH-R-Ab binding and bioassays were highly correlated in the samples of both study groups (binding immunoassay vs luciferase bioassay, r =.91, P <.001, binding vs cyclic adenosine monophosphate (cAMP) bioassay, r = 0.86, P <.001, and luciferase vs cAMP bioassay, r = 0.71, P =.006). The serological results correlated with the course of the extrathyroidal clinical parameters of GD, that is, clinical activity score and proptosis. Conclusion: Targeting the FcRn markedly reduces the disease-specific TSH-R-Ab in patients with GD. The novel and rapid TSH-R-Ab bioassay improves diagnosis and management of patients with GD. Competing Interests: Disclosure The JGU Medical Center receives research-associated funding from Quidelortho, San Diego, CA, USA, and from Immunovant Inc., New York City, NY, USA. G.J.K. consults for Immunovant and QuidelOrtho. (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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