Search results for "Thyrotropin receptor"
showing 10 items of 19 documents
A cyclic peptide significantly improves thyroid function, thyrotropin-receptor antibodies and orbital mucine /collagen content in a long-term Graves’…
2021
BALB/c mice which received long-term immunizations of adenovirus (Ad) expressing thyrotropin receptor A-subunits (TSHR) developed stable Graves' disease (GD). TSHR-derived cyclic peptide 19 (P19) was identified as effective therapy in this model.In Ad-TSHR mice, we investigated shorter disease intervals up to 4 months for histological alterations of the orbits, fine tuning of anti-TSHR antibodies (Ab) and free thyroxine (fT4) hormone levels by using novel detection methods in an independent laboratory. Therapy (0.3 mg/kg P19 or vehicle) was given intravenously after the fourth Ad-TSHR immunization (week 11) and continued until week 19.Thyrotropin binding inhibitory immunoglobulins (TBII, br…
TSH/IGF-1 Receptor Cross Talk in Graves' Ophthalmopathy Pathogenesis.
2016
AbstractContext:The TSH receptor (TSHR) is considered the main target of stimulatory autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO); however, it has been suggested that stimulatory IGF-1 receptor (IGF-1R) autoantibodies also play a role.Objective:We previously demonstrated that a monoclonal stimulatory TSHR antibody, M22, activates TSHR/IGF-1R cross talk in orbital fibroblasts/preadipocytes obtained from patients with GO (GO fibroblasts [GOFs]). We show that cross talk between TSHR and IGF-1R, not direct IGF-1R activation, is involved in the mediation of GO pathogenesis stimulated by Graves' autoantibodies.Design/Setting/Participants:Immunoglobulins were purified from the…
Prospective Trial of Functional Thyrotropin Receptor Antibodies in Graves Disease
2019
Abstract Context Scarce data exist regarding the relevance of stimulatory (TSAb) and blocking (TBAb) thyrotropin receptor antibodies in the management of Graves disease (GD). Objective To evaluate the clinical utility and predictive value of TSAb/TBAb. Design Prospective 2-year trial. Setting Academic tertiary referral center. Patients One hundred consecutive, untreated, hyperthyroid GD patients. Methods TSAb was reported as percentage of specimen-to-reference ratio (SRR) (cutoff SRR < 140%). Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bovine thyrotropin (TSH, thyroid stimulating hormone) alone (cutoff > 40% inhibitio…
Subclinical hyperthyroidism due to a thyrotropin receptor (TSHR) gene mutation (S505R).
2006
Aim: To identify the molecular defect by which non-autoimmune subclinical hyperthyroidism was caused in a 6-mo-old infant who presented with weight loss. Methods: Congenital non-autoimmune hyperthyroidism is caused by activating germline mutations in the thyrotropin receptor (TSHR) gene. Therefore, the TSHR gene was sequenced directly from the patient's genomic DNA. Results: Molecular analysis revealed a heterozygous point mutation (S505R) in the TSHR gene as the underlying defect. Conclusion: A constitutively activating mutation in the TSHR gene has to be considered not only in patients with severe congenital non-autoimmune hyperthyroidism, but also in children with subclinical non-autoimm…
Analytical performance and clinical utility of a bioassay for thyroid-stimulating immunoglobulins.
2013
Abstract The analytical performance and the clinical utility of a thyrotropin receptor (TSHR)–stimulating immunoglobulin (TSI) bioassay were compared with those of a TSHR-binding inhibitory immunoglobulin (TBII) assay. Limits of detection (LoD) and quantitation (LoQ), assay cutoff, and the half-maximal effective concentration (EC50) were measured. Dilution analysis was performed in sera of hyperthyroid patients with Graves disease (GD) during antithyroid treatment (ATD). Titer was defined as the first dilution step at which measurement of TSI or TBII fell below the assay cutoff. The LoD, LoQ, cutoff, and EC50 of the bioassay were 251-, 298-, 814-, and 827-fold lower than for the TBII assay.…
A Novel Anti-CD40 Monoclonal Antibody, Iscalimab, for Control of Graves Hyperthyroidism—A Proof-of-Concept Trial
2019
Abstract Context The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves disease (GD) by promoting autoreactive B-cell activation. Objective Evaluate efficacy and safety of a human, blocking, nondepleting anti-CD40 monoclonal antibody, iscalimab, in hyperthyroid patients with GD. Design Open-label, phase II proof-of-concept study. Setting Multicenter. Patients Fifteen with GD. Intervention Patients received 5 doses of iscalimab at 10 mg/kg intravenously over 12 weeks. Main outcome measures Thyroid-related hormones and autoantibodies, plasma soluble CD40, free CD40 on B cells, soluble CXCL13, pharmacokinetics, and safety were assessed. Results The iscalima…
High Titers of Thyrotropin Receptor Antibodies Are Associated With Orbitopathy in Patients With Graves Disease.
2018
AbstractContextSerum TSH receptor autoantibody (TSH-R-Ab) is a biomarker of Graves disease (GD). Studies have shown that the levels of this TSH-R-Ab have clinical significance.ObjectiveTo differentiate between thyroidal GD only and Graves orbitopathy (GD + GO).DesignControlled, follow-up study.SettingAcademic tertiary referral center for GD + GO.SubjectsSixty patients with GD, GD + GO, and controls.InterventionSerial serum dilution analyses with six automated, ELISA, and cell-based assays for TSH-R-Ab.Main Outcome MeasureDifferentiation among GD phenotypes.ResultsAll undiluted samples of hyperthyroid-untreated GD patients were positive with the six assays but became negative at dilution 1:9…
Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves' Hyperthyroidism: A Phase I Study
2019
Background: Graves' disease is one of the most common autoimmune conditions, but treatment remains imperfect. This study explores the first-in-human use of antigen-specific immunotherapy with a combination of two thyrotropin receptor (TSHR) peptides (termed ATX-GD-59) in Graves' hyperthyroidism. Methods: Twelve participants (11 female) with previously untreated mild to moderate Graves' hyperthyroidism were enrolled in a Phase I open label trial to receive 10 doses of ATX-GD-59 administered intradermally over an 18-week period. Adverse events, tolerability, changes in serum free thyroid hormones, and TSHR autoantibodies were measured. Results: Ten subjects received all 10 doses of ATX-GD-59,…
Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins
2000
After autoimmune inflammation, interactions between CD95 and its ligand (CD95L) mediate thyrocyte destruction in Hashimoto's thyroiditis (HT). Conversely, thyroid autoimmune processes that lead to Graves' disease (GD) result in autoantibody-mediated thyrotropin receptor stimulation without thyrocyte depletion. We found that GD thyrocytes expressed CD95 and CD95L in a similar manner to HT thyrocytes, but did not undergo CD95-induced apoptosis either in vivo or in vitro. This pattern was due to the differential production of TH1 and TH2 cytokines. Interferon gamma promoted caspase up-regulation and CD95-induced apoptosis in HT thyrocytes, whereas interleukin 4 and interleukin 10 protected GD …
Analytical Performance and Validation of a Bioassay for Thyroid-Blocking Antibodies
2016
A cell-based bioassay for the measurement of thyroid blocking autoantibodies (TBAb) has been recently reported. The analytical performance and validation of this bioassay is assessed and described.Chinese hamster ovary cells expressing a chimeric thyrotropin receptor were treated with bovine (b) TSH and different concentrations of an immunoglobulin G (IgG) monoclonal human TBAb (K1-70). TBAb was measured as a function of luciferase activity relative to bTSH alone and expressed as percent inhibition. Results obtained in the chimeric cell line were compared with those of a wild-type cell line. Analytical performance studies were subsequently performed with the chimeric cell line only.Immunode…