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Thyroglobulin (TG) and thyroperoxidase (TPO), both involved in thyroid hormone synthesis, represent major autoantigens in thyroid autoimmune disease. Despite numerous studies, the emergence, pathophysiological significance and role of autoantibodies to TG and TPO remain elusive. The recent identification of a new category of thyroid-specific autoantibody interacting with both TG and TPO (TGPO autoantibodies) offers a new opportunity in the study of thyroid autoimmunity. To gain a better insight into the significance of these TGPO autoantibodies, measurement in individual samples appeared necessary. The unique property of TGPO autoantibodies, simultaneous binding to TG and TPO, was used to set up a sandwich method which combined coated TG and radio-iodinated TPO. This method was found to be strictly specific for TGPO autoantibodies and sensitive enough to assay TGPO autoantibodies in serum. In humans, TGPO autoantibodies were found in most of the sera with high TG and TPO autoantibody titres, but not in sera negative for TG autoantibodies, whatever the TPO autoantibody titre. Furthermore, high TGPO autoantibody titres were found in sera strongly cytotoxic for cultured porcine thyroid cells. However, significant correlation of TGPO autoantibody titre was observed neither with TG and TPO autoantibody titres (n = 48) nor with complement-dependent cytotoxicity (n = 50). TGPO antibody assay was also performed in individual plasma of CBA/J mice immunized with either human TG (n = 6) or human TPO (n = 6). Immunization with TG induced high levels of not only TG but also TGPO antibodies, which exhibited a strong reactivity for TPO and whose binding to TG and TPO was fully inhibited by TG. In contrast, immunization with TPO induced high levels of only specific TPO antibodies accompanied by low levels of specific TG antibodies. In this case TGPO antibodies were not detected. Of note, TG- and TPO-immunized mice mounted an immune response against their own TG, but did not exhibit histological signs of thyroiditis. Large panels of TG and TPO MoAbs were also investigated with this method: 18/25 TG MoAbs and only 1/13 TPO MoAbs were found cross-reactive. Taken together, these data provide evidence that TGPO antibodies are effectively present in individual patients and TG-immunized mice, are different from specific TG and TPO antibodies, and may derive from natural B cell repertoire by autoimmune processes involving TG and not TPO.

In one study on patients with thyroideopathies at Hospital Escuela, Tegucigalpa, Honduras, four patients were found with psychosis, and high values of antimicrosomal, and antithyroid globulin antibodies. In one control study, the presence of ATA is associated to a high incidence of family antecedents of immunological disease, thyroids, and mental diseases--especially schizophrenia.

Fluid from fourteen thyroid cysts has been submitted to electrophoretic and immunochemical procedures in order to describe the biochemical structure of the fluid. Two patterns have been identified: a pattern showing a composition similar to that of normal serum ("serum-like"); thyroglobulin concentration is low, IgG are sometimes above normal and hTg-Abs are frequently detectable. A second pattern shows instead, a picture in which serum protein fractions are largely denatured and not identifiable ("denatured"); thyroglobulin concentration has been found markedly increased. It is suggested that in "serum like" the formation of the cysts occurs in the interstitium, whereas in the "denatured" type cyst the hemorrhagic necrosis appears to be the consequence of a massive damage of the follicular tissue.

The present report deals with the measurement of serum thyroglobulin (Tg) in various thyroid disorders by using radioimmunoassay (RIA). The results were as follows: 1) A specific and simple solid-state RIA for the measurement of Tg in human serum was used. This system was a direct RIA using plactic cups coated with crude anti-thyroglobulin antibodies (anti-Tg) and 125I labeled purified anti-Tg. The purification of anti-Tg was performed by affinity chromatography using Tg-Sepharose, as an immunoadsorbent. 2) Affinity chromatography was carried out using a modification of the method of Cuatrecasas. The immunoadsorbent (Tg-Sepharose conjugate) was used in a column procedure for the isolation of anti-Tg from globulin fractions obtained from Hashimoto's sera. The elution was performed with 4M NaI or 0.17M Glycine-HCl with pH 2.3. The eluted materials contained a very small amount of Tg which was removed by Sephadex G-200 chromatography using the same elution buffer. The high purity of the anti-Tg obtained was demonstrated by the fact that almost all of the final product was bound with Tg by using Sepahdex G-200 chromatography. 3) A direct RIA consisting of two incubation steps was applied for Tg measurement. During the first incubation, standard Tg or Tg in serum was bound to the antibody coated cup. After washing, equal amounts of radioactive purified anti-Tg were incubated with the bound Tg. The cups were then washed again, and counted separately. The radioactive counts thus obtained, increased with the amounts of Tg bound to the anti-Tg by the first incubation. The sensitivity of the assay was 4 ng/ml. T3 and T4 did not cross-react against Tg, and did not interfere with the binding between Tg and 125I-anti-Tg. A dilution curve was constructed using the serum of a patient with Graves' disease; the post-operative serum contained a very high level of Tg. This curve paralleled the standard curve. By adding constant Tg to a normal serum or Graves' serum, Tg recovery was good. However, in regard to Hashimoto's serum, Tg recovery was unsatisfactory. 4) Serum Tg concentrations were measured in patients with various thyroid disorders. ..