Clinical relevance of thyroid-stimulating immunoglobulins in graves' ophthalmopathy.

Abstract

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 < 0.001) and severity (r=0.81, P < 0.001) of GO. All 59 patients with GO with diplopia were TSI positive, and 50 of 59 patients (85%) were TBII positive. Among patients with moderate-to-severe and mild GO, 75 of 75 (100%) and 31 of 33 (94%) were TSI positive compared with TBII positivity in 63 of 75 (84%) and 24 of 33 (73%), respectively. The TSI levels were higher in moderate-to-severe versus mild GO (489%±137% vs. 251%±100%, P < 0.001). Chemosis and GO activity predicted TSI levels alone (P < 0.001, multivariable analysis). The TSI levels were higher in patients with chemosis (527%±131%) than in patients without chemosis (313%±127%, P < 0.001).

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.

• Authors: Katharina A Ponto, Michael Kanitz, Paul D Olivo, Susanne Pitz, Norbert Pfeiffer, George J Kahaly
• Journal: Ophthalmology (Ophthalmology) Vol. 118 Issue 11 Pg. 2279-85 (Nov 2011) ISSN: 1549-4713 [Electronic] United States
• PMID: 21684605 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Immunoglobulins, Thyroid-Stimulating
• thyrotropin-binding inhibitory immunoglobulin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biological Assay
• Biomarkers (blood)
• Cross-Sectional Studies
• Diplopia (blood, physiopathology)
• Female
• Graves Ophthalmopathy (immunology, physiopathology)
• Humans
• Immunoglobulins, Thyroid-Stimulating (blood)
• Male
• Middle Aged
• Prevalence
• Sensitivity and Specificity
• Severity of Illness Index
• Young Adult