甲状腺疾患における抗TSH受容体抗体の意義に関する研究
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概要
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Graves' immunoglobulins have been shown to displace labeled TSH bound to thyroid plasma membranes. However, TSH displacing activity (TDA) could not be detected in all of the cases. Its relationship to thyroid function and to clinical symptoms has not yet been clearly demonstrated. The present study was carried out to clarify the specificity and pathogenetic importance of TDA of IgGs mainly found in patients with Graves' disease. <BR>IgG was purified using DEAE cellulose column chromatography. A radioreceptor assay was carried out according to the method of Smith and Hall. Human thyroid adenylate cyclase stimulator (HTACS) activity of IgG was determined according to the method of Orgiazzi et al. with slight modifications. Mean %B/F, calculated as percentage of B/F to that of the control obtained in the absence of IgG, was 98.5 ± 8.3 (SD), 94.7 ± 7.8, 90.0 ± 9.3 and 75.5 ± 11.0% in the presence of 1, 5, 10 and 20 mg/ml of normal IgGs, respectively. Since this decrease in %B/F with normal IgGs was considered as a nonspecific inhibitory effect of IgG itself, %B/F of sample IgG was corrected by dividing the obtained data by the mean %B/F of normal IgGs at each concentration, which was designated as corrected %B/F (C-%B/F). The percentage of patients with untreated Graves' disease who showed positive TDA increased as did IgG concentration up to 10 mg/ml of IgG. When assayed at 10 mg/ml of IgG, 40 out of 48 cases (83.3%) were TDA positive in untreated Graves' disease, 3 out of 18 (16.7%) in Hashimoto's thyroiditis, 2 out of 12 (16.7%) in thyroid neoplasm and 5 out of 9 (5 5.6%) in subacute thyroiditis. <BR>All the untreated patients with Graves' disease including the displacing activity negative ones, showed a dose-dependent decrease in C-%B/F up to 10 mg/ml of IgG. On the other hand, the values obtained in most patients with thyroid neoplasm and Hashimoto's thyroiditis showed random dose-independent variations within normal ranges. In 5 out of 6 patients with subacute thyroiditis, dose-dependent decreases in C-%B/F were observed. <BR>In patients with untreated Graves' disease, TDA was significantly correlated to the size of struma and to the values of Hertel's exophthalmometry. With antithyroid drug treatment, the numbers of TDA positive patients gradually decreased. Among the patients treated for more than a year, only 26% were TDA positive. Six out of 9 patients who had been TDA positive at the time of cessation of therapy relapsed immediately thereafter, while 8 out of 11 TDA negative patients remained euthyroid for more than 9 months. HTACS activity was positive in all of the 8 patients with untreated Graves' disease examined. IgG with stronger TDA tended to show higher HTACS activity. <BR>On the other hand, serum IgG from a mother with nongoitrous hypothyroidism exhibited strongly positive TDA; C-%B/F being 4.1%. IgGs obtained from umbilical cord blood of her hypothyroid neonates (nonidentical twins) demonstrated positive TDA as strong as that of herself, which became undetectable in the surviving baby 6 months after birth, when her thyroid function became normal. Maternal IgG was devoid of HTACS activity, and it definitely inhibited thyroidal adenylate cyclase stimulation induced by TSH. The presence of a blocking antibody to TSH receptor in maternal serum and its trans-placental transfer to her children were suggested. <BR>In summary, correlations between TDA and clinical symptoms, courses, prognosis and HTACS strongly suggested the pathogenetic role of anti-TSH receptor antibody in Graves' disease. However, the presence of a blocking antibody against TSH receptor in non-goitrous hypothyroidism suggested the diversity of anti-TSH receptor antibody concerning biological activity.
- 日本内分泌学会の論文