Impaired immune regulation after radioiodine therapy for Graves’ disease and the protective effect of Methimazole

Abstract

Both therapies for Graves' disease (GD), radioactive iodine (RAI) and antithyroid drugs (ATD), were reported to have specific immune effects. We aimed at investigating the effects of RAI therapy on cellular subsets involved in immune regulation. We conducted a thirty day follow-up prospective cohort study of adult patients. Patients eligible for RAI therapy at our centre were approached. Twenty seven patients with GD were recruited, among whom 11 were treated with ATD. Twenty-two healthy subjects (HS) were also studied. Over time, frequency of regulatory T cells (Treg) and of invariant natural killer T cells (iNKT), along with Treg cell-mediated suppression and underlying mechanisms, were monitored in the peripheral blood. Variance in frequency of Treg and iNKT after RAI therapy was higher in GD patients than in HS over time (p < 0.0001). Reduced Treg suppressive function was observed after RAI therapy in GD patients (p = 0.002). ATD medication prior to RAI dampened these outcomes: less variation of Treg frequency (p = 0.0394), a trend toward less impaired Treg function, and prevention of reduced levels of suppressive cytokines (p < 0.05). Shortly after RAI therapy, alterations in immunoregulatory cells in patients with GD were observed and partially prevented by an ATD pretreatment. Worsening of autoimmunity after RAI was explained in previous studies by enhanced immune activity. This study adds new highlights on immune regulation deficiencies after therapeutic interventions in thyroid autoimmunity.

Limited cutaneous systemic sclerosis arising in a patient with Graves’ disease

“…This phenomenon has been explained by the release of preformed thyroid hormones and autoantibodies into the bloodstream following RAI-mediated destruction of the thyroid gland 1. It has also been associated with increased levels of peripheral blood lymphocytes (CD3+, CD4+ and CD3+ HLA-DR+), which are instrumental in the pathogenesis of SSc 16. However, the absence of active eye disease in our patient plus the complete resolution of her hyperthyroid state after RAI both make this theory less likely.…”

Impact of Radioiodine Treatment on Doppler Flow Parameters in the Central Retinal Artery and Ophthalmic Artery in Patients With Hyperthyroidism

“…Radioiodine treatment in patients with Graves disease can enhance the autoimmune response and lead to a higher TRAb concentration 16 . Another factor underlying the increased autoimmune response is a disturbance in the number and suppressive function of natural killer cells and conventional T cells 17 . A statistically significant increase in the PSV in both the CRA and OA in both patient groups is thus related to an abrupt change in the hormonal status after radioiodine therapy and is derived from intensified peripheral hyperkinetic circulation dependent on cardiac muscle performance 18 …”

“…16 Another factor underlying the increased autoimmune response is a disturbance in the number and suppressive function of natural killer cells and conventional T cells. 17 A statistically significant increase in the PSV in both the CRA and OA in both patient groups is thus related to an abrupt change in the hormonal status after radioiodine therapy and is derived from intensified peripheral hyperkinetic circulation dependent on cardiac muscle performance. 18 In both groups, there were no statistically significant differences in RI values (in both the CRA and OA) across 3 consecutive measurements (before iodine treatment and 2 weeks and 4 weeks after radioiodine administration).…”

Percentage and function of CD4+CD25+ regulatory T cells in patients with hyperthyroidism

“…Hyperthyroidism is the most common organ-specific autoimmune disease and the most important reason for Graves' ophthalmopathy ( 13 – 15 ). Although the pathogenesis of hyperthyroidism has not been completely elucidated, recent studies indicated that the change of immunologic function may be closely correlated with the occurrence of hyperthyroidism ( 16 , 17 ). The maintenance of immune function is closely associated with immunosuppressive cells existing in the body.…”