Increase in immunoglobulin G3-secreting cells in intractable Graves' disease.

Isotype switching of immunoglobulin (Ig)-secreting cells is regulated by a set of cytokines. In the present study, we studied the relation between the number of peripheral blood mononuclear cells spontaneously secreting IgG, IgM, IgA, and their subclasses and the disease severities in autoimmune thyroid diseases. Ig-secreting cells were measured by enzyme-linked immunospot (ELISPOT) assay in 99 euthyroid patients with Graves' disease (GD) or Hashimoto's disease (HD) and 13 normal subjects. The number of IgG3-secreting cells was significantly higher in patients with intractable GD who had been undergoing treatment with antithyroid drugs for more than 5 years but who did not go into remission than in patients with GD in remission. This number correlated significantly with the serum level of thyrotropin receptor antibody (TRAb) in all patients with GD. These data suggest that the number of IgG3-secreting cells whose isotype switching is stimulated by interleukin (IL)-10 and IL-4 may be related to the disease severity of GD and to the level of TRAb after long-term treatment with antithyroid drugs.