Anti-thyroid Hormone Antibodies Research Articles

The Effect of Levothyroxine and Selenium versus Levothyroxine Alone on Reducing the Level of Anti-thyroid Peroxidase Antibody in Autoimmune Hypothyroid Patients.

Background:Due to the prevalence of autoimmune hypothyroidism and its effects on physical and mental health it is necessary to provide a treatment which is also effective in preventing the progression of sub-clinical hypothyroidism in these patients. This study aims to investigate the effect of selenium supplementation on of anti-thyroid hormone antibodies in these patients.Materials and Methods:In a randomized clinical trial, 70 patients with autoimmune hypothyroidism randomly divided into two groups of 35 each, the first group was treated with oral selenium treatment with levothyroxine (LT4) and to the second group along with LT4, placebo was also prescribed. Serum selenium level, thyroid hormones and anti-thyroid hormone antibodies before and after 3 months of treatment in both groups, were determined, and the results were analyzed using SPSS software.Results:The mean of the serum anti-thyroid peroxidase serum level in the intervention group before and after treatment was 682.18 ± 87.25 and 522.96 ± 47.21 and the difference before and after treatment was statistically significant (P = 0.021). The level of this antibody before and after treatment in the control group was 441 ± 53.54 and 501.18 ± 77.68, and no significant differences between two groups were observed before and after treatment (P = 0.42).Conclusion:Selenium supplementation may help to reduce the levels of antibodies in patients with autoimmune hypothyroidism.

The Risk from Anti-Thyroid Hormone Antibody Interference in Neonatal Congenital Hypothyroidism Screening

Neonatal congenital hypothyroidism screening is considered to be one of the most effective newborn screening strategies. Neonatal screening for congenital hypothyroidism involves the analysis of thyroid hormone and thyrotropin levels using an immunoassay based technique. Immunoassays are also prone to analytical problems such as assay interference. Immunoassays used for thyroid hormone measurement are known to be affected from anti-thyroid hormone antibody interference. This is the first reported case of interference presumably caused by anti-thyroid hormone antibodies transferred from mother to child during pregnancy, affecting the measurement of free-thyroxine in a cord-blood sample. We report a case of a full-term newborn with presumed anti-thyroid hormone antibody interference present in both cord blood and subsequent venous blood samples. In the context of a newborn screening programme based solely on thyroxine measurement, this is an important finding, since it has the potential to cause false negative screening results.

Spuriously high thyroid hormone concentrations measured by chemiluminescent immunoassay attributable to anti-iodothyronine antibodies in a dog

A 2.5-year-old female English setter was presented with clinicopathological findings suggestive of hypothyroidism. Thyroid-stimulating hormone (TSH: 4.3 ng/ml, normal <0.5), but also free thyroxine (FT4: 77 pmol/l, normal 7.7–48), total...

Nature and significance of calcium oxalate crystals in normal human thyroid gland. A clinicopathological and immunohistochemical study.

To elucidate the significance and nature of calcium oxalate crystals in the thyroid, we studied these crystals clinicopathologically and immunohistochemically in 182 normal thyroids from patients autopsied within 5 h of death. Under polarized light, calcium oxalate crystals showed brilliant birefringence and were invariably found within the colloid. The crystals were found in 73.1% of all cases but were more prevalent and denser in older individuals, with the highest prevalence (85.2%) being observed in those over 70 years of age. No crystals were seen in those under 10 years of age. Although underlying diseases seemed to have little influence, post-mortem delay apparently affected the prevalence and density of occurrence since the crystals tended to disappear with hours after death. An immunohistochemical study using anti-thyroid hormone antibodies revealed that the crystals were within negatively or weakly stained colloid and were not common in strongly stained colloid. These findings support the hypothesis that the occurrence of calcium oxalate crystals in normal human thyroid is associated with a low functional state of the thyroid follicles.

Thyroid hormones in human follicular fluid and thyroid hormone receptors in human granulosa cells

To demonstrate the presence of thyroid hormone in human follicular fluid (FF) and the binding of antithyroid hormone antibodies in human granulosa cells (GCs). Follicular fluids and GCs collected from women undergoing oocyte retrieval after superovulation. In Vitro Fertilization-America/Allegheny General Hospital and Reproductive Sciences Research Laboratories, the Department of Obstetrics and Gynecology, The Medical College of Pennsylvania/Allegheny Campus. Follicular fluid levels of triiodothyronine (T3) determined by a microparticle enzyme immunoassay and FF levels of thyroxine (T4) determined by a fluorescence polarization immunoassay. Three anti-thyroid receptor antibodies were used to determine the presence of thyroid receptor. The binding of these antibodies in GCs was assessed by fluorescent microscopy and flow cytometry. Both T3 and T4 were present in the FF of eight patients studied. A large majority of the samples of individual fluids fell within the normal range for serum. There was a positive correlation between serum T4 values and FF T4 values. The three antithyroid receptor antibodies showed positive nuclear staining of GCs by fluorescent microscopy. The antibody to all thyroid hormone receptors yielded 35% positive cells by flow cytometry, and the site specific antibody for either the alpha-1 or beta-1 receptors yielded 78% and 44% positive cells, respectively. These data demonstrated, for the first time, the presence of T3 and T4 in human FF and the presence of T3 binding sites in human GCs and suggest a role for thyroid hormone in the regulation of human GCs.

Antithyroid hormone antibodies induced by interferon-alpha

Antithyroid hormone antibodies induced by interferon-alpha

Two cases of Graves’ disease with antithyroid hormone antibodies: Implication on the role of thyroglobulin as an antigen

We have experienced two cases of Graves' disease with antithyroid hormone autoantibodies (Case 1: anti-T4; Case 2: anti-T3) who finally underwent subtotal thyroidectomy after antithyroid drug treatment. Using serial sera obtained before and after operation, the correlation between titers of antithyroglobulin (anti-Tg) and anti-T4 or anti-T3 autoantibodies was examined in each case. There was a significant positive correlation between titers of anti-T4 (Case 1, r = 0.90, p less than 0.05), or anti-T3 (Case 2, r = 0.64, p less than 0.01) and anti-Tg antibodies. Using the homogenate of the thyroid tissue, it was found that the sole iodoprotein in the thyroid gland in each patient was 660 KDa Tg. In addition, Tg purified from the thyroid gland from Case 2 showed different immunological activity with normal Tg in two out of four murine monoclonal anti-Tg antibodies tested. On the other hand, Tg from Case 1 had identical immunological activity with normal Tg in every four monoclonal antibodies. These results are consistent with the view that the antigen responsible for the development of antithyroid hormone autoantibodies is Tg, at least in our two cases. The reason for the persistence of anti-T3 autoantibodies in Case 2, despite the subtotal thyroidectomy, could be due to some unidentified structural abnormalities of Tg which was detected only by the monoclonal anti-Tg antibodies.

Effect of 8-anilino-1-naphthalene sulfonic acid (ANS) on the interaction between thyroid hormone and anti-thyroid hormone antibodies

Effect of 8-anilino-1-naphthalene sulfonic acid (ANS) on the interaction between thyroid hormone and anti-thyroid hormone antibodies was examined. Addition of 5.1 × 10 6 or 6.3 × 10 6 molar excess of ANS, respectively, enhanced the binding of 125I-T 3 or 125I-T 4 to their respective autoantibodies. However, further increase in ANS concentration resulted in a decrease in binding. These results suggest that the optimum concentration of ANS for the detection of anti-thyroid hormone antibodies is 5 ~ 6 × 10 6 molar excess of ANS to 125I-T 3 or 125I-T 4. On the other hand, addition of 10 4 molar excess of ANS concentration decreased the binding of 125I-insulin to anti-insulin antibodies. It was therefore suggested that the effect of ANS could be a nonspecific one and likely due to its negative charge.

Two cases of Graves' disease with anti-thyroid hormone antibodies

Two cases of Graves' disease with anti-thyroid hormone antibodies

Autoimmune recognition of thyroglobulin and thyroid hormones in rabbits

Two rabbits (RG-1, RG-2) were immunized with rabbit thyroglobulin (RTg) purified from thyroid glands of four other normal rabbits of the same strain, and bled serially. Antisera were obtained at different times after the first immunization and kept separately and studied. Production of anti-RTg as well as anti-thyroid hormone antibodies such as anti-thyroxine (T4) and anti-triiodothyronine (T3) antibodies was observed in both rabbits. Physicochemical parameters of anti-RTg antibodies with RTg, T4, and T3 were calculated in two selected antisera (70-day and 253-day) of each of the rabbits, using a Scatchard plot. Extraction of serial sera from both rabbits disclosed the presence of larger amounts of T3 and T4 in immune sera than in preimmune serum. Examination of pathology of thyroid glands and kidneys in both rabbits was negative for the lesions of autoimmune thyroiditis and immune nephritis. These results indicate that anti-Tg as well as anti-thyroid hormone autoantibodies can be raised without thyroid pathology in rabbit by immunization with autologous Tg.

Production of anti-human thyroglobulin and anti-thyroid hormone antibodies in rabbits immunized with homogenate of human papillary cancer tissue

Papillary cancer tissue of the thyroid gland removed from each of three patients was homogenized in phosphate buffer followed by centrifugation. Each of three rabbits was immunized with each of the supernatants (TC-1, TC-2, TC-3). These rabbits were immunized on days 0, 7, 14, and 21, and serum from each rabbit, obtained 4 weeks after the first immunization, was examined for the presence of anti-human thyroglobulin (HTg), anti-thyroxine (T4), and anti-triiodothyronine (T3) antibodies. Production of anti-HTg antibodies was observed in all three rabbits. In addition, despite the low content of iodine, T3, and T4 in thyroglobulin that had been purified from the papillary cancer tissues (p-HTg), production of anti-T4 and anti-T3 was observed in two of the three rabbits, and the other immunized with TC-1 showed anti-T4 but no anti-T3 antibodies. The significance of the production of anti-thyroid hormone antibodies in rabbits with respect to the antigenic structure of p-HTg with low content of iodine and thyroid hormone is discussed.

Genetic control of the production of anti-thyroid hormone antibodies in mice immunized with human thyroglobulin.

Various strains of mice with different H-2 and Igh-I allotypes were immunized with human thyroglobulin (HTg) and genetic control of the production of anti-thyroid hormone antibodies was examined. Anti-HTg antisera obtained from different strains of mice were examined for the presence of anti-thyroid hormone antibodies. At least one Ir-gene which controls the production of anti-T4 antibodies by immunization with HTg was identified in the I-A subregion. The presence of Ir-genes outside the H-2 was also suspected. Concerning the production of anti-T3 antibodies, only three strains (B10.A, C3H.SW, BALB/cJ) were high responders and therefore we were unable to identify the Ir-gene for them. These results indicate the presence of Ir-gene which controls the immune response in mice against thyroid hormone and suggest that the anti-thyroid hormone antibodies observed in various thyroidal and non-thyroidal disorders could be anti-HTg antibodies. The significance of genetic control of the production of anti-thyroid hormone antibodies in mice immunized with HTg is discussed.

Concentrations of free thyroxine, total thyroxine, and total triiodothyronine in rabbits immunized with human thyroglobulin.

Levels of serum free thyroxine, total triiodothyronine and total thyroxine were measured in two rabbits (TG-1, TG-2) which had been immunized with human thyroglobulin and produced both anti-thyroglobulin and anti-thyroid hormone antibodies. Despite the presence of both anti-triiodothyronine and -thyroxine antibodies, levels of serum free thyroxine in serial sera obtained from a rabbit (TG-1) stayed within normal range up to 249 days after the first immunization, whereas in the other rabbit (TG-2), serum free thyroxine concentrations of serial sera declined after three immunizations and stayed at lower levels than normal range up to 249 days. Extraction of serial sera from both rabbits disclosed the presence of larger amounts of triiodothyronine and thyroxine in immune sera than preimmune sera. From these results, it is concluded that the presence of anti-thyroid hormone antibodies per se can reduce serum level of free thyroxine in rabbits.

Production of anti-human thyroglobulin and anti-thyroid hormone antibodies in rabbits immunized with human thyroglobulin.

Two rabbits (TG-1, TG-2) were immunized with human thyroglobulin (HTg) and bled serially. Antisera were obtained at different times after the first immunization and kept separately and studied. In both rabbits production of anti-HTg, and anti-thyroid hormone antibodies such as anti-thyroxine (T4) and anti-triiodothyronine (T3) antibodies was observed. Binding parameters of anti-HTg antibodies with HTg, T4, and T3 were calculated in two selected antisera (70-day and 249-day). The Scatchard's plots of these antibodies were all curve-linear and were analyzed in two components: one, higher binding constant (Ka1) and smaller binding capacity (Cap1) and the other, lower binding constant (Ka2) and larger binding capacity (Cap2). Ka1 values of anti-HTg, anti-T4, and anti-T3 antibodies in sera from TG-1 obtained from 70-day and 249-day bleeding were 1.1 X 10(10) M-1, 6.0 X 10(9) M-1. 7.9 X 10(8) M-1 and 1.7 X 10(10) M-1, 6.5 X 10(9) M-1, 1.0 X 10(9) M-1, respectively. Those from TG-2 were 1.7 X 10(10) M-1, 1.8 X 10(9) M-1, 6.4 X 10(8) M-1 and 2.0 X 10(10) M-1, 3.1 X 10(9) M-1, 1.6 X 10(9) M-1, respectively. The significance of the production of anti-HTg and anti-thyroid hormone antibodies in rabbits immunized with HTg in relation to the antigenic structure of HTg molecule was discussed.

Investigations on the mechanism(s) of the production of anti-thyroid hormone antibodies 4: the effect of adjuvant on the immune response to human thyroglobulin

Forty-five female DDYK mice were divided into three groups and immunized with different preparations of human thyroglobulin (HTg). Group 1 mice were immunized subcutaneously in the back with HTg emulsified with FCA. Group 2 mice were immunized subcutaneously in the back with HTg dissolved in PBS. Group 3 mice were immunized with HTg dissolved in PBS and FCA separately in the right (HTg) and left (FCA) of the back. After the fourth immunization (45 days after the first immunization), antisera as well as thyroid glands were obtained, and titers of anti-HTg, anti-T3, anti-T4 and the presence of lesions of autoimmune thyroiditis were examined. In group 1 mice, titers of anti-HTg and anti-T4 antibodies were significantly higher than those of the other two groups, whereas titers of anti-T3 antibodies were significantly lower than those of the other two groups. In group 1 mice, a significant correlation between titers of anti-T3 and anti-T4 antibodies was observed, whereas in group 2 and group 3 mice, no such correlation was observed. The incidence of lesions of autoimmune thyroiditis was significantly higher in group 2 and group 3 mice than in group 1 mice. Thus emulsification of HTg with FCA had inhibitory effects on the induction of experimental thyroiditis in mice immunized with HTg. These results indicate the possibility that FCA has a modulatory effect both quantitatively and qualitatively on the immune response against HTg in mice.

Production of anti-rabbit thyroglobulin and anti-thyroid hormone antibodies in rabbits immunized with rabbit thyroglobulin

Production of anti-rabbit thyroglobulin and anti-thyroid hormone antibodies in rabbits immunized with rabbit thyroglobulin

Participation of ir-gene on the production of anti-thyroid hormone antibodies in mice immunized with human thyroglobulin

Participation of ir-gene on the production of anti-thyroid hormone antibodies in mice immunized with human thyroglobulin

Investigations on the mechanism(s) of the production of anti-thyroid hormone antibodies 3:Production of anti-rabbit thyroglobulin and anti-thyroid hormone antibodies in rabbits immunized with rabbit thyroglobulin

Recently, the presence of anti-thyroid hormone antibodies has been reported in many cases of thyroidal and non-thyroidal disorders. In order to elucidate the immunological mechanism(s) in the production of anti-thyroid hormone antibodies, we immunized outbred rabbits and mice with different H-2 and Igh allotypes with human thyroglobulin (HTg) and showed that the production of both anti-HTg and anti-thyroid hormone antibodies is genetically controlled. In our present study, rabbit thyroglobulin (RTg) was purified from 4 rabbit thyroid glands and was immunized in two rabbits (RG-I, RG-2). The two rabbits were then serially bled and tested for the presence of anti-RTg and anti-thyroid hormone antibodies. In both rabbits, the production of anti-RTg and anti-thyroid hormone antibodies was observed. The binding constant of anti-RTg, anti-T4 and anti-T3 antibodies in RG-1 were 6 X 10(9)M-1, 9.5 X 10(8)M-1, 4.6 X 10(8)M-1, and those in RG-2 were 6.5 X 10(9)M-1, 5.6 X 10(8)M-1, 1.6 X 10(8)M-1, respectively. These results further strengthen the possibility that the antigen of the anti-thyroid hormone antibodies observed in various disorders so far reported is the HTg molecule. In addition, the fact that anti-RTg antibodies had a higher binding constant and capacity than anti-thyroid hormone antibodies suggests that the antigenic site(s) of RTg, which contains thyroid hormones, is not highly immunogenic.

An Investigation on the Mechanism (s) of the Production of Antithyroid Hormone Antibodies

Recently anti-thyroid hormone antibodies have been found in many cases of thyroidal and non-thyroidal disorders. However, the exact mechanism(s) of production of anti-thyroid hormone antibodies in these patients is so far obscure. Thyroxine (T4) and triiodothyronine (T3) are haptens and are not immunogenic in free form. In this respect, human thyroglobulin (HTg) has long been suggested as an antigen of the anti-thyroid hormone antibodies observed in them because it carries thyroid hormones on its surface. In our previous communication, we reported the production of anti-HTg antibodies and anti-thyroid hormone antibodies in two rabbits and various strains of mice immunized with HTg. In order to elucidate the gene(s) which controls the production of anti-HTg and anti-thyroid hormone antibodies, various strains of mice which have different H-2 and Igh allotypes were immunized with HTg. The titers of anti-HTg and anti-thyroid hormone antibodies were measured, and the locus (loci) which controls the immune response against them was determined. Our present investigation has revealed that the Ir-gene(s) which controls the production of anti-HTg and anti-T4 antibodies is located in the I-A subregion. Concerning the production of anti-T4 antibodies in mice, the presence of Ir-gene(s) outside of H-2 is also suggested. The significance of the genetic mechanisms controlling the immune response against thyroid hormones in various thyroidal disorders is discussed.

Investigations on the mechanism(s) of the production of anti-thyroid hormone antibodies. 1. Anti-thyroid hormone antibodies in rabbits and mice immunized with human thyroglobulin

Recently we reported anti-thyroid hormone antibodies in two cases of Hashimoto's thyroiditis and one case of Graves' disease. In order to elucidate the immunological mechanism (s) of production of anti-thyroid hormone antibodies, animal studies using outbred rabbits and inbred mice were performed.Two rabbits (TG-1, TG-2) were immunized with human thyroglobulin and bled serially. In both rabbits production of anti-human thyroglobulin and anti-thyroid hormone antibodies such as thyroxine (T4), triiodothyronine (T3) and 3, 3', 5'-triiodothyronine (rT3) were observed. These results suggested to us the presence of the immune response gene (s) which controls the immune response against human thyroglobulin and thyroid hormones.Accordingly, fifteen strains of mice which had different Ig h allotypes and H-2 loci were immunized with human thyroglobulin and antibody activities against human thyroglobulin as well as thyroid hormones were examined. Although there were high and low responders, all strains of mice produced anti-human thyroglobulin antibodies. Among them, some strains of mice were high responders against T4 and T3. There was no high responder against rT3.These experimental results clearly indicate the presence of immune response gene (s) in mice against human thyroglobulin and thyroid hormones. The significance of the genetic control of the immune response against thyroid hormones in relation to the presence of antithyroid hormones antibodies in various thyroidal disorders was discussed.