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RESEARCH PRODUCT

Clinical Relevance of Thyroid-Stimulating Immunoglobulins in Graves' Ophthalmopathy

Katharina A. PontoPaul D. OlivoNorbert PfeifferSusanne PitzMichael KanitzGeorge J. Kahaly

subject

endocrine systemmedicine.medical_specialtyendocrine system diseasesbiologybusiness.industryGraves' diseaseAutoantibodymedicine.diseaseThyrotropin receptorGraves' ophthalmopathyOphthalmologychemistry.chemical_compoundEndocrinologychemistryInternal medicineImmunopathologyImmunologymedicinebiology.proteinThyroid Stimulating ImmunoglobulinCyclic adenosine monophosphateAntibodybusiness

description

Purpose Thyroid-stimulating immunoglobulins (TSIs) likely mediate Graves' ophthalmopathy (GO). The clinical relevance of these functional autoantibodies was assessed in GO. Design Cross-sectional trial. Participants A total of 108 untreated patients with GO. Methods Thyroid-stimulating immunoglobulins, assessed with a novel bioassay, bind to the thyrotropin receptor (TSHR) and transmit signals for cyclic adenosine monophosphate (cAMP)-dependent activation of luciferase gene expression. The cAMP/cAMP response element-binding protein/cAMP-regulatory element complex induces luciferase that is quantified after cell lysis. The TSI levels were correlated with activity and severity of GO and compared with a TSHR binding inhibitory immunoglobulin (TBII) assay. Main Outcome Measures Thyroid-stimulating immunoglobulins, activity and severity of GO, diplopia, and TBII. Results Thyroid-stimulating immunoglobulins were detected in 106 of 108 patients (98%) with GO. All 53 hyperthyroid patients were TSI positive versus 47 patients (89%) who were TBII positive. All 69 patients with active GO were TSI positive, whereas only 58 of 69 patients (84%) were TBII positive. Thyroid-stimulating immunoglobulins correlated with the activity ( r =0.83, P r =0.81, P P P P Conclusions Thyroid-stimulating immunoglobulins show more significant association with clinical features of GO than TBII and may be regarded as functional biomarkers for GO. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

https://doi.org/10.1016/j.ophtha.2011.03.030