Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease

Abstract

The prevalence and clinical relevance of thyroid stimulating hormone (TSH) receptor (TSHR) blocking antibodies (TBAb) in patients with autoimmune thyroid disease (AITD) was investigated. Serum TBAb were measured with a reporter gene bioassay using Chinese hamster ovary cells. Blocking activity was defined as percentage inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off 40% inhibition). All samples were measured for TSHR stimulatory antibody (TSAb) and TSHR binding inhibiting immunoglobulins (TBII). A total of 1079 unselected, consecutive patients with AITD and 302 healthy controls were included. All unselected controls were negative for TBAb and TSAb. In contrast, the prevalence of TBAb-positive patients with Hashimoto's thyroiditis and Graves' disease was 67 of 722 (9·3%) and 15 of 357 (4·2%). Of the 82 TBAb-positive patients, thirty-nine (48%), 33 (40%) and 10 (12%) were hypothyroid, euthyroid and hyperthyroid, respectively. Ten patients were both TBAb- and TSAb-positive (four hypothyroid, two euthyroid and four hyperthyroid). Thyroid-associated orbitopathy was present in four of 82 (4·9%) TBAb-positive patients, with dual TSHR antibody positivity being observed in three. TBAb correlated positively with TBII (r = 0·67, P < 0·001) and negatively with TSAb (r = -0·86, P < 0·05). The percentage of TBII-positive patients was higher the higher the level of inhibition in the TBAb assay. Of the TBAb-positive samples with > 70% inhibition, 87% were TBII-positive. Functional TSHR antibodies impact thyroid status. TBAb determination is helpful in the evaluation and management of patients with AITD. The TBAb assay is a relevant and important tool to identify potentially reversible hypothyroidism.

2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

“…A meta-analysis of 21 studies showed that the overall pooled sensitivity and specificity of the serum TSH-R-Ab concentration measured with second-and third-generation binding assays were 97 and 98%, respectively [25]. In contrast, the highly sensitive cell-based bioassays [26][27][28][29][30][31][32][33] exclusively differentiate between the TSH-R-stimulating Ab (TSAb) and TSH-R-blocking Ab [34,35]. Also, TSAb is a highly sensitive and predictive biomarker for the extrathyroidal manifestations of GD [36][37][38][39][40][41][42] as well as a useful predictive measure of fetal or neonatal hyperthyroidism [43,44].…”

Pathogenetic Role of Thrombocytes in the Development of Autoimmune Pathology of the Thyroid Gland

“…We have shown that an increased level of platelet aggregation and its generation (vesicular structures formed predominantly during activation and death of cells), as well as greater agonist susceptibility, is crucial for hemostatic platelet function. Excessive production of microparticles induced by constant cell activation may contribute to the development of chronic inflammatory processes and propensity to autoimmune diseases [11][12][13]. According to the results of our study, we hypothesized that PMPs can interact with circulating autoantibodies and C1q involved in the formation of immune complexes, which can be a pathophysiological cause of the immune response.…”

Alternating hyperthyroidism and hypothyroidism in Graves’ disease

“…Previously, it was thought that people with GD only had stimulating TSH receptor antibodies. However, now it is increasingly recognized that both TSAb and TBAb can be produced concurrently in the same patient; the presence of hyperthyroidism or hypothyroid may depend on the balance between stimulating and blocking antibodies . The phenomenon of TSH receptor antibody switching between stimulating and blocking is infrequent .…”

“…Out of 98 TSAb predominant hyperthyroidism, only two subjects later developed TBAb‐dominant hypothyroidism . In a recent publication where TSAb and TBAb were quantified with a reporter gene bioassay using Chinese hamster ovary cells, <1% (10/1079) patients with autoimmune thyroid disease which included Hashimoto's thyroiditis and GD, were positive for both TSAb and TBAb …”

“…7 In a recent publication where TSAb and TBAb were quantified with a reporter gene bioassay using Chinese hamster ovary cells, <1% (10/1079) patients with autoimmune thyroid disease which included Hashimoto's thyroiditis and GD, were positive for both TSAb and TBAb. 5 Unfortunately, we do not have the availability of TBAb measurement at our institution and only recently have been able to quantify TSAb. Monitoring of TRAb is important in pregnant women with GD, as TSAb and TBAb can cause neonatal thyrotoxicosis and hypothyroidism, respectively, and affect neonatal development.…”