title: Highly variable sensitivity of five binding and two bio-assays for TSH-receptor antibodies.
abstract: OBJECTIVE
  TSH-receptor (TSHR) antibodies (Ab) can be measured with binding or bio-assays. Sensitivity and specificity of five binding and two bio-assays were compared.
  
  
  METHODS
  TSHR-blocking (TBAb) and TSHR-stimulating (TSAb) Ab were measured with reporter bio-assays. Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bTSH alone. TSAb was reported as percentage of specimen-to-reference ratio (SRR%). TSHR-binding inhibitory immunoglobulins (TBII) were measured with Kronus, Dynex, Kryptor, Cobas, and Immulite.
  
  
  RESULTS
  Sixty patients with Graves' disease (GD), 20 with Hashimoto's thyroiditis (HT), and 20 healthy controls (C) were included. C tested negative in all assays (specificity 100 %) while all 60 hyperthyroid GD patients tested positive in the TSAb bio-assay (sensitivity 100 %). Among these 60 GD patients, 20 had low TSAb positivity (SRR% 140-279), but were TBII positive in only 20 (100 %), 7 (35 %), 9 (45 %), 11 (55 %), and 18 (90 %) using the Kronus, Dynex, Kryptor, Cobas, and Immulite, respectively. In 20 moderate TSAb-positive (SRR% 280-420) patients, TBII tested positive in 20 (100 %), 14 (70 %), 13 (65 %), 16 (80 %), and 19 (95 %), respectively. The high (SRR% > 420) TSAb-positive patients were all TBII positive. All 20 hypothyroid HT patients tested TBAb positive (sensitivity 100 %) in the bio-assay while they tested TBII positive in 20 (100 %), 18 (90 %), 20, 20, and 18, respectively. Results obtained with two luminometers correlated for TSAb positive (r = 0.99, p < 0.001), TBAb positive (r = 0.88, p < 0.001), and C (r = 0.86, p < 0.001). None of the binding assays differentiated between TSAb and TBAb.
  
  
  CONCLUSIONS
  Sensitivity is highly variable between binding and bio-assays for TSHR-Abs.
authors.affiliation: Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Diana
authors.affiliation: Endocrine Practice, Mainz, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Wüster
authors.affiliation: Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kanitz
authors.affiliation: Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany. kahaly@ukmainz.de.
authors.forename: G J
authors.initials: GJ
authors.lastname: Kahaly
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011989:Receptors, Thyrotropin / Q000276:immunology*; D013959:Thyroid Diseases / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin; C094372:thyrotropin-binding inhibitory immunoglobulin
keywords: Binding assays; Bio-assays; Sensitivity; Specificity; TSH-receptor binding inhibitory immunoglobulins; Thyroid-blocking antibodies; Thyroid-stimulating antibodies