A Study on Anti-T3 and Anti-T4 Autoantibodies Found in Two Sisters with Juvenile Hypothyroidism due to Hashimoto's Thyroiditis

We previously reported that two sisters with juvenile hypothyroidism due to Hashimoto's thyroiditis (case 1: 13 years old, case 2: 10 years old) had antibodies against T3 and T4, and that the titers of these antibodies decreased but remained above normal levels even in the euthyroid state during L-T4 treatment. In our further investigations we found the binding of 125I-rT3 to serum gamma-globulin in both cases in the pre-treatment period. This binding was completely inhibited by the addition of unlabelled rT3. In addition to these findings, we also found the presence of anti-rT3 antibodies in two rabbits (TG-1, TG-2) immunized with human thyroglobulin. Since it has been suggested that autoantibodies against thyroglobulin cross-react with T3 and T4, we examined the specificities of anti-rT3 antibodies which were found in both cases and in the two rabbits in order to clarify the role of thyroglobulin in rT3 antibody production. The association constants and binding capacities of rT3 antibodies in cases 1 and 2 were 2.9 X 10(8) M -1 and 50 ng/ml serum, and 2.2 X 10(9) M -1 and 1.5 ng/ml serum, respectively. Cross reactivities of these anti-rT3 antibodies with T3 and T4 were 1.8% and 276% in case 1, and 0.24% and 38% in case 2, respectively. These results suggest that anti-rT3 antibodies in case 1 are anti-T4 antibodies interacting with rT3, and those in case 2 are antibodies against rT3 which have a high cross reactivity with T4. In both cases, however, cross reactivities with T3 were very small. Cross reactivities of anti-rT3 antibodies with T3 and T4 in TG-1 and TG-2 were 4.0% and 53%, and 53% and 182%, respectively. These data were compatible with those obtained from both cases. The observation that anti-rT3 antibodies found in two sisters and two rabbits immunized with human thyroglobulin had similar characteristics in terms of cross reactivities with T3 and T4 suggests the role of thyroglobulin as an antigen in rT3 antibody production in both patients.