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

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.

Interferon-gamma ELISPOT detecting reactivity of T cells to TSH receptor peptides in Graves' disease.

OBJECTIVE: While thyrotrophin receptor (TSHR) is recognized as the main autoantigen in Graves' disease (GD), the actual antigen specificity of T cells that infiltrate the thyroid and the orbit is unknown. Identifying T cell responses to TSHR peptides has been difficult in the past due to the low frequency of autoreactive T cells and to the diversity of the putative epitopes identified by proliferation assays. METHODS: We used the interferon-gamma ELISPOT assay to identify T cell reactivity to TSHR peptides in patients with GD. Peripheral blood T cells were exposed in vitro to four pools of 10 overlapping TSHR peptides. RESULTS: T cells from 11 of 31 (35%) patients with GD and 1 of 22 (4%) healthy controls reacted to at least one peptide pool (P = 0·009). Mean time since diagnosis was 3·2 years in responder patients and 5·6 years in nonresponders (P = 0·07). In two patients, T cell reactivity was observed shortly after radioiodine treatment and not thereafter. CONCLUSIONS: Our findings demonstrate that the ELISPOT assay is effective to test T cell reactivity in patients with GD and that patients with GD have significantly more interferon-gamma responses towards TSHR peptides than controls. The data suggest that screening for T cell responses in patients with GD might be more efficient in recent-onset disease or after radioiodine treatment.