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

• Published in: Endocrine Vol. 52; no. 3; pp. 587 - 596
• Main Authors: Côté-Bigras, Sarah, Tran, Viet, Turcotte, Sylvie, Rola-Pleszczynski, Marek, Verreault, Jean, Rottembourg, Diane
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2016
• Subjects: Adult; Aged; Antithyroid Agents - therapeutic use; Autoimmunity - drug effects; Autoimmunity - radiation effects; Cells, Cultured; Cytoprotection - drug effects; Cytoprotection - immunology; Diabetes; Endocrinology; Female; Graves Disease - drug therapy; Graves Disease - immunology; Graves Disease - radiotherapy; Humanities and Social Sciences; Humans; Internal Medicine; Iodine Radioisotopes - therapeutic use; Killer Cells, Natural - drug effects; Killer Cells, Natural - pathology; Killer Cells, Natural - radiation effects; Male; Medicine; Medicine & Public Health; Methimazole - therapeutic use; Middle Aged; multidisciplinary; Original Article; Radiation Injuries - prevention & control; Science; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - radiation effects; Young Adult; Radioactive iodine; Regulatory T cells; Antithyroid drugs; Graves’ disease; Natural killer T cells
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-015-0832-2

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.