Thyrotrophin receptor antibody concentration and activity, several years after treatment for Graves’ disease

Abstract

Summary Objective TSH receptor antibodies (TRAb) are responsible for autoimmune hyperthyroid disease (Graves’ disease; GD) with TRAb levels tending to decrease following treatment. Measurement of TRAb activity during follow‐up could prove valuable to better understand treatment effectiveness. Study design TRAb concentration and stimulating (TSAb) and blocking (TSBAb) activity of patient serum were assessed following different treatment modalities and follow‐up length. Methods Sixty‐six subjects were recruited following treatment with carbimazole (n = 26), radioiodine (n = 27) or surgery (n = 13). TRAb, TPOAb, TgAb and GADAb were measured at a follow‐up visit as well as bioassays of TSAb and TSBAb activity. Results Forty‐five per cent of all patients remained TRAb‐positive for more than one year and 23% for more than 5 years after diagnosis, irrespective of treatment method. Overall, TRAb concentration fell from a median (IQR) of 6.25 (3.9‐12.7) to 0.65 (0.38‐3.2) U/L. Surgery conferred the largest fall in TRAb concentration from 11.4 (6.7‐29) to 0.58 (0.4‐1.4) U/L. Seventy per cent of TRAb‐positive patients were positive for TSAb, and one patient (3%) was positive for TSBAb. TRAb and TSAb correlated well (r = 0.83). In addition, 38/66 patients were TgAb‐positive, 47/66 were TPOAb‐positive and 6/66 were GADAb‐positive at follow‐up. Conclusions TRAb levels generally decreased after treatment but persisted for over 5 years in some patients. TRAb activity was predominantly stimulatory, with only one patient demonstrating TSBAb. A large proportion of patients were TgAb/TPOAb‐positive at follow‐up. All treatment modalities reduced TRAb concentrations; however, surgery was most effective.

Experimental Reproduction of Dynamic Fluctuation of TSH Receptor–Binding Antibodies Between Stimulation and Inhibition

“…Patients with GD have polyclonal TSHR-Abs that include stimulating and blocking components in their sera, and the ratio of those components may vary from patient to patient and may change during the clinical course [18]. Actually, we often experience the discrepancies that are observed in the detection of TSHR-Abs between a binding assay and bioassay in various clinical views of AITDs (Fig.…”

Changes in Th9 and Th17 lymphocytes and functional cytokines and their relationship with thyroid-stimulating hormone receptor antibodies at different stages of graves’ disease

“…This is related to fluctuations in immune response in the body, but it is also largely affected by treatment type (15, 16). Simultaneously, the initial expression and TRAb titer changes also guide the choice and modification of clinical treatment strategies and can accurately predict the prognosis and short-term recurrence risk of GD treatment (17). TRAb persistence suggests that GD patients require ablation therapy or long-term maintenance of low-dose antithyroid drugs.…”

TSH receptor specific monoclonal autoantibody K1‐70TM targeting of the TSH receptor in subjects with Graves' disease and Graves' orbitopathy—Results from a phase I clinical trial

“…Current therapies for GD usually target the ability of the thyroid to produce thyroid hormones and include antithyroid drugs (ATD) and destruction of the thyroid using radioiodine or surgical thyroidectomy . 3 However, they often have variable and unsatisfactory outcomes, 3 highly dependent on the treatment modality used 4 . In a study of 549 GD patients, 21% were still positive for TSHR autoantibodies (TRAb) after 5 years of continuous therapy with ATD 5 …”

“…3 However, they often have variable and unsatisfactory outcomes, 3 highly dependent on the treatment modality used. 4 In a study of 549 GD patients, 21% were still positive for TSHR autoantibodies (TRAb) after 5 years of continuous therapy with ATD. 5 Standard treatment for moderate to severe Graves' orbitopathy (GO) includes systemic steroids and/or surgical interventions as appropriate, but is often unsatisfactory.…”

“… 3 However, they often have variable and unsatisfactory outcomes, 3 highly dependent on the treatment modality used. 4 In a study of 549 GD patients, 21% were still positive for TSHR autoantibodies (TRAb) after 5 years of continuous therapy with ATD. 5 …”