title: Clinical relevance of thyroid-stimulating immunoglobulins in graves' ophthalmopathy.
abstract: OBJECTIVE
  Thyroid-stimulating immunoglobulins (TSIs) likely mediate Graves' ophthalmopathy (GO). The clinical relevance of these functional autoantibodies was assessed in GO.
  
  
  METHODS
  Cross-sectional trial.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Department of Ophthalmology, University Medical Center, Mainz, Germany.
authors.forename: Katharina A
authors.initials: KA
authors.lastname: Ponto
authors.forename: Michael
authors.initials: M
authors.lastname: Kanitz
authors.forename: Paul D
authors.initials: PD
authors.lastname: Olivo
authors.forename: Susanne
authors.initials: S
authors.lastname: Pitz
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.forename: George J
authors.initials: GJ
authors.lastname: Kahaly
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001681:Biological Assay; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D004172:Diplopia / Q000097:blood / Q000503:physiopathology; D005260:Female; D049970:Graves Ophthalmopathy / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018828:Immunoglobulins, Thyroid-Stimulating; C094372:thyrotropin-binding inhibitory immunoglobulin