Changes in expression of T-helper (Th) 1- and Th2-associated chemokine receptors on peripheral blood lymphocytes and plasma concentrations of their ligands, interferon-inducible protein-10 and thymus and activation-regulated chemokine, after antithyroid drug administration in hyperthyroid patients with Graves’ disease

Abstract

Objective: Although Graves' disease is considered an autoantibody-mediated, T-helper 2 (Th2)-dominant disease, Th1-dominance may prevail in its initial phase. We longitudinally investigated Th1/Th2 balance in untreated hyperthyroid patients with Graves' disease after treatment of methimazole (MMI), an antithyroid drug. Design: University clinic outpatients were studied prospectively. Patients: Subjects included 23 untreated hyperthyroid patients with Graves' disease and 17 agematched control subjects. Methods: Before and after treatment, we measured Th1-and Th2-associated chemokine receptors (CXCR)3 and CCR4, on peripheral blood lymphocytes using flow cytometry, as well as plasma concentrations of their ligands, interferon-inducible protein (IP)-10 and thymus and activationregulated chemokine (TARC). Results: The percentage of CXCR3-expressing cells among CD4C T lymphocytes and plasma IP-10 was significantly higher in hyperthyroid Graves' disease patients than in controls. At 12 and 24 weeks after initiation of MMI, percentage of CXCR3-expressing CD4 C T lymphocytes had decreased significantly, while the percentage of CCR4-expressing CD4 C T lymphocytes had increased significantly at 24 weeks. The CXCR3/CCR4 ratio had decreased significantly at 24 weeks. Plasma concentrations of IP-10 had decreased significantly at 12 and 24 weeks. Plasma concentrations of TARC also had decreased significantly at 24 weeks. Conclusions: In hyperthyroid patients with Graves' disease in the active phase, Th1 cells rather than Th2 cells predominated among peripheral blood lymphocytes. After initiation of MMI, an ongoing transition from Th1 to Th2 dominance occurred. 156 623-630 European Journal of Endocrinology

Function of regulatory T-cells improved by dexamethasone in Graves' disease

“…Following the improvement in Treg cell function, the proportion of Th2 cells decreased with DEX treatment in this study. Although GD's classification as a typical Th1-dominant disease is up for debate, some studies have suggested that Th1 cells play a role in the induction of GD (9,27). In this study, we found an increase in the proportion of Th1 cells in GD patients, which corresponds to the result of other reports (9,28).…”

“…The balance between Th1 and Th2 lymphocytes may determine the outcome of autoimmune diseases. Recent studies have suggested that both Th1 and Th2 cells participate in the pathogenesis of GD, and the roles of Th1 and Th2 on the pathogenesis of GD are diverse at different phases of GD (9). The development of GD is related to the production of antithyroid antibodies, which suggests the importance of Th2 cells in the pathogenesis of GD.…”

“…The imbalance of Th1/Th2 cells caused by Treg cell dysfunction may determine the outcome of autoimmune diseases (8). Although GD is considered an autoantibody-mediated Th2-dominant disease, Th1 dominance may prevail in its initial phase (9).…”

Abnormal Chemokine Receptor Profile on Circulating T Lymphocytes from Nonallergic Asthma Patients

“…Organ-specific or systemic immune system-mediated diseases are characterized by the involvement of circulating lymphocytes [14,15,16]. These findings would support the hypothesis of alterations in circulating T cells from nonallergic asthmatic patients.…”

The Concept of Vitamin D Sufficiency and Insufficiency in Graves’ Disease

“…7 In this regards it can be said that the suppression of Th1 response by Vitamin D may counteract the onset of Graves' Disease, as Th1 dominance seems to be involved in the induction of the disease. 8 Many studies highlighted the role of vitamin D in the development of thyroid autoimmune diseases (AITD), which has been also demonstrated in animal models. 9 In human studies on the association of vitamin D levels with antithyroid antibodies, lower 25(OH)D levels were found in subjects with higher levels of antithyroid antibodies compared with those who were negative for thyroid autoimmunity.…”