Thyrotropin Receptor Autoantibody Assessment in Thyroid Eye Disease: Does the Assay Type Matter?

Purpose: Thyroid receptor antibodies can quantify thyroid eye disease activity, predict outcomes and aid timing of interventions. The type and generation of assay is frequently unspecified, complicating meta-analyses. To determine the clinical andbiochemical relationships between a second-generation thyrotropin receptor-binding inhibition antibody (TRAb) immunoassay,detecting stimulatory and blocking antibodies, with the thyroid stimulating immunoglobulin (TSI) bridging immunoassaydetecting the stimulatory component only. Methods: Retrospective review of 100 consecutive patients attending a regional specialist service. For each patient and visit,both a TRAb and TSI were performed, and a clinical activity score (CAS) recorded. Results: A significant positive correlation between TRAb and TSI (rho = 0.828, p < 0.01) but a weaker correlation betweenthe assays and CAS (TRAb: rho = 0.439, p < 0.01; TSI: r = 0.357, p < 0.01) were found. In 10% of the episodic data, patientshad a TRAb level that was disproportionately high (39.41 ± 52.84 IU/L), compared to their TSI levels (9.53 ± 12.10 IU/L) with ahigher-than-average CAS (2.47 ± 1.78; range, 0-5). Within 12 months of diagnosis, a significant positive correlation betweenCAS and TRAb (rho = 0.503, p < 0.01) as well as between CAS and TSI (rho = 0.329, p < 0.01) were found. In patients with adiagnosis over 12 months, the correlation with CAS for both TSI and TRAb were Spearman rank correlation coefficient of 0.347(p < 0.01) and 0.327 (p < 0.01), respectively. Conclusions: TRAb and TSI correlate strongly and to a lesser extent with the CAS. For most patients, TRAb can be replacedwith the more economical TSI. TRAb also correlates better with newly diagnosed, more active patients than TSI. In a subsetof patients, blocking antibodies may play a significant pathogenic role, requiring different treatment and monitoring. Furtherstudies are required to investigate this relationship.