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An Elevation of Serum Immunoglobulin E Provides a New Aspect of Hyperthyroid Graves’ Disease

Department of Medicine, Kashiwa City Hospital (T.Y., T.N., Y.I., A.T.), Kashiwa, Chiba 277; Department of Medicine, Dokkyo Koshigaya Hospital, Dokkyo University School of Medicine (A.S.), Koshigaya, Saitama 343-8555; Second Department of Medicine, Faculty of Medicine, University of the Ryukyus (I.K.), Nishihara, Okinawa 903-0215; and First Department of Medicine, University of Occupational and Environmental Health (S.E., Y.T.), Yawatanishiku, Kitakyushu 807-8555, Japan

Address all correspondence and requests for reprints to: Akira Sato, M.D., Department of Medicine, Dokkyo Koshigaya Hospital, Dokkyo University School of Medicine, Koshigaya, Saitama 343-8555, Japan. E-mail: asato{at}dokkyomed.ac.jp

In hyperthyroid Graves’ disease, short-term methimazole is sufficient to induce lasting remission in some patients, but even long-term treatment fails to do so in others. We have evaluated the role of autoimmune abnormalities in the helper T cell type 2 (TH2)-interleukin-13 (IL-13)-TSH receptor system in maintaining hyperthyroidism by comparing IgE levels in patients with various thyroid diseases.

One hundred and ninety-three patients with hyperthyroid Graves’ disease were treated with methimazole, and blood samples were obtained to measure serum levels of T₄, T₃, TSH, thyroglobulin, antimicrosomal antibody, TSH binding inhibitory Ig (TBII), thyroid-stimulating antibody, thyroid stimulation-blocking antibody, IgE, interferon-, IL-4, and IL-13. Elevation of serum IgE (170 U/mL) was found in 35.5% of patients with hyperthyroid Graves’ disease, and serum levels of T₄, T₃, antimicrosomal antibody, and TBII were significantly greater in patients with IgE elevation than in those with normal serum IgE. During methimazole treatment, there was a parallel decrease in the serum T₄ concentration in the presence or absence of an IgE elevation. However, there was a significantly smaller decrease in TBII in patients with elevated IgE than in those with normal IgE. As a result, the remission rate was significantly greater in patients with normal IgE than in those with IgE elevation. Serum levels of IL-13 were elevated in 64.7% of patients with IgE elevation in the absence of detectable TH1 marker, interferon-.

These findings suggest that in one third of patients with hyperthyroid Graves’ disease, TH2 cells are stimulated and secrete excess amounts of IL-13, which subsequently stimulates B cells to synthesize more TSH receptor antibody and IgE, so that during methimazole treatment TBII decreases less in patients with IgE elevation, producing a lower remission rate.

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