Evaluation of the first fully automated immunoassay method for the measurement of stimulating TSH receptor autoantibodies in Graves' disease

Background: Thyroid stimulating hormone (TSH) receptor autoantibodies (TRAb) are pathogenetic and diagnostic hallmarks of Graves' disease (GD). Three varieties of TRAb have been described: stimulating (S-TRAb), blocking (B-TRAb), and apoptotic (A-TRAb) autoantibodies. Very recently, the first immunoassay method (Immulite TSI assay, Siemens Healthcare Diagnostics) declared to measure serum S-TRAb concentration, has been made available in an automated commercial platform. The aim of the study was to evaluate the ability of this new test to identify patients suffering from GD, in comparison with two current IMA methods for total TSH receptor autoantibodies (T-TRAb) measurement. Methods: Sera of 383 subjects [72 patients with untreated GD, 55 patients with autoimmune thyroiditis (AIT), 36 patients with multinodular non-toxic goiter, 100 patients with other non-thyroid autoimmune diseases (NTAD) and 120 healthy subjects (HS)] were evaluated. Results: The threshold obtained by receiver-operating characteristic (ROC) analysis was 0.54 IU/L, very similar to that proposed by the manufacturer (0.55 IU/L). -Thyroid-stimulating immunoglobulins (TSI) were-positive in all GD patients and negative in all but three controls (clinical sensitivity and specificity of 100% and 98.7%, respectively). Passing and Bablok regression analysis and Bland-Altman plot showed an acceptable agreement between TSI Immulite assay and other two immunoassay methods (Cobas/Elecsys, Roche and TRAK RIA, BRAHMS Thermo Scientific). Conclusions: The diagnostic performance of fully automated Immulite TSI assay in GD patients is at least comparable to that of current TRAb immunoassays (IMAs) suggesting the possibility of including such assay in rapid and cost-saving diagnostic and monitoring algorithms. However, our results do not provide full evidence that this assay is specific for S-TRAb only, and future studies comparing Immulite TSI assay to stimulating activity are required.