Functional polymorphisms affecting Th1 differentiation are associated with the severity of autoimmune thyroid diseases.

The prognosis for autoimmune thyroid diseases (AITDs), such as Hashimoto's disease (HD) and Graves' disease (GD), varies among patients. Interleukin (IL)-12 and IL-18 also induce Th1 differentiation, and SOCS1 (Suppressor of cytokine signaling 1) and TIM-3 (T cell immunoglobulin and mucin domain-3) are known to be negative regulators of Th1 cells. To clarify the association of functional polymorphisms in the IL12, IL12Rβ1, IL18, SOCS1 and TIM3 genes with the intractability and severity of autoimmune thyroid disease (AITD), we genotyped these polymorphisms in 151 GD patients, including 61 patients with intractable GD and 51 patients with GD in remission, in 140 HD patients, including 59 patients with severe HD and 55 patients with mild HD, and in 74 healthy controls.

Ratio of serum IgG3 to total IgG concentration and goiter size are independent factors in intractability of Graves' disease.

Peripheral immunoglobulin (Ig) G(3)-secreting cells and serum concentrations of interleukin (IL)-10, a class-switching factor to IgG(3)-secreting cells, increase in patients with intractable Graves' disease (GD). However, they are not practical for laboratory tests. To find more stable and easily detectable markers of disease intractability or disease severity in patients with GD or Hashimoto's disease (HD), we examined the serum concentration of IgG(3) in 58 euthyroid GD patients who had been undergoing antithyroid drug treatment for more than 5 years but still must continue drug treatment to maintain a euthyroid state (intractable GD), 26 GD patients who had maintained a euthyroid state for more than 2 years without any treatment (GD in remission), 20 untreated, thyrotoxic GD patients, 40 euthyroid HD patients treated with thyroxine (5 men and 35 women), 13 untreated, euthyroid HD patients, and 39 healthy volunteers.