AUTOANTIBODIES TO THYROGLOBULIN CROSS REACTING WITH IODOTHYRONINES

Abstract

Serum thyroxine [T4] was consistently unmeasurable by radioimmunoassay in an elderly patient with myxedema after successful treatment with oral T4. Abnormal binding of T4 was suspected and was due to the presence in serum of antibodies of the IgG variety. The characteristics of these antibodies with respect to their binding of T4, triiodothyronine (T3), reverse T3 (rT3) and human thyroglobulin (Tg) were systematically studied. Three preparations of Tg, and T4, T3 and rT3 were examined for their ability to compete with 125I-Tg, 125I-T4, 125I-T3 and 125I-rT3 for binding to the antibodies. For each tracer used the order of competitive efficiency was Tg > T4 > T3 > rT3. This provides for the 1st time direct evidence that iodothyronine reacting antibodies occurring in man are generated against Tg. All 3 iodothyronines were able to inhibit tracer binding of labeled iodothyronines completely, the order of effectiveness being T4 > T3 > rT3, suggesting antibodies with 1 type of binding site and that these were probably raised against a Tg sequence incorporating T4, although there was some evidence for the existence of a minor subpopulation of antibodies with higher specificity for T3. Complete displacement of labeled Tg by cold iodothyronines was not possible. The experimental evidence suggests 2 classes of Tg antibodies, 70% of which were directed towards the T4 containing region, and 30% directed against other part(s) of the Tg molecule. Despite the presence of such Tg antibodies conventional hemagglutination tests of the patient''s serum for Tg antibodies were negative.