Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.8 (thyroid peroxidase)
3,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the in vitro effects of interleukin-1-beta (IL-1-beta), interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) on the induction of anti-thyroperoxidase (anti-TPO), anti-thyroglobulin (anti-Tg), and IgG-secreting cells (SC) by cultures of pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cells (PBMC) obtained from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), and controls (C). The effect of human thyroglobulin (Tg) together with cytokines was also studied. No differences in the numbers of PWM-induced IgG-SC were found. However, greater numbers of PWM-induced anti-TPO-SC were observed in the HT preparations compared to C, either with or without the addition of Tg (p < 0.05). Inhibition of numbers of IgG-SC with certain cytokines in all 3 groups of preparations was observed (0.01 < p < 0.05). Decreased numbers of anti-TPO-SC were noted in HT preparations after exposing cells to IL-2 and TNF-alpha. Induction of anti-TPO-SC after addition of Tg plus cytokines was significantly lower in HT than in the other 2 groups. In contrast, induction of anti-TPO-SC in C was markedly increased by all cytokines, which was enhanced by Tg. These data suggest that cytokines play a role in auto-antibody regulation in auto-immune thyroid disease (AITD).
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PMID:In vitro effects of cytokines and human thyroglobulin on the induction of antibody-secreting cells in patients with auto-immune thyroid disease. 830 34

Anti-CD3 (OKT3) MoAb is a mitogenic agent which activates lymphocytes. We have studied the effects of murine anti-human OKT3 MoAb (IgG1) alone or in combination with IL-2, human thyroglobulin (Tg) and thyroperoxidase (TPO) antigens on the proliferation of whole peripheral blood mononuclear cells (PBMC) (including monocytes) or subtypes (T, CD4+, CD8+, B) as measured by tritiated thymidine (3H-TdR) incorporation. B cell differentiation was studied by measuring numbers of IgG-secreting cells and specific anti-TPO/anti-Tg-secreting cells by SPOT ELISA. PBMC or lymphocyte subtypes, obtained from 45 patients with Hashimoto's thyroiditis (HT), 40 Graves' disease (GD) and 51 normal controls were cultured in 96 microtitre plates for 6 days in the presence of OKT3 MoAb at final concentrations 25-250 ng/ml, IL-2 15 U/ml, Tg and TPO (1 micrograms/ml). Then cultures were pulsed with 0.2 microCi 3H-TdR/well and incorporation was measured after 18 h. IgG and anti-TPO/Tg-secreting cells were detected at 7 days. Higher proliferative responses from whole PBMC preparations in response to any of the combinations including OKT3 MoAb were observed in the HT preparations, while the basal values were the lowest. IL-2 alone increased these responses markedly, but equally in all groups. IL-2 in combination with OKT3 had an additive effect on proliferation, with higher responses in HT. Tg and TPO antigens did not change these responses. Most HT preparations responded with their maximum proliferation to the lowest concentration of OKT3 MoAb (25 ng/ml), whereas in GD and control preparations of PBMC these responses were shifted to higher concentrations (250 ng/ml); even with those, proliferation was not so enhanced in controls when compared with HT and GD preparations. In contrast, the proliferative responses of T cells alone and subpopulations of CD8+ suppressor/cytotoxic cells were decreased in HT preparations compared with controls. Monocytes were necessary for proliferation. In the subpopulation of B cells (> 95% pure) and CD4+ helper/inducer cells, differences did not reach significance. In spite of the effect on proliferation, OKT3 MoAb only mildly but significantly increased the numbers of IgG-secreting cells in HT and GD preparations and did not stimulate synthesis of specific antibodies. Our data suggest that the increased proliferative responses of whole PBMC to OKT3 MoAb in HT preparations might be due to insufficient activation of T suppressor/cytotoxic cells.
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PMID:Study of induction of activation of human peripheral blood mononuclear cells with a non-activating form of anti-CD3 MoAb in autoimmune thyroid disease (AITD). 844 62

The presence of sexual steroid receptor proteins in thyroid tissue has been previously demonstrated by biochemical means. The aim of this study was to determine the estrogen (ER) and progesterone (PR) receptors in malignant (12 papillary and 1 follicular carcinoma) and nonmalignant (19 multinodular goiters, 1 Graves' disease, 1 Hashimoto's thyroiditis) thyroid diseases using immunocytochemical assay employing monoclonal anti-ER and anti-PR antibodies and the peroxidase-antiperoxidase technique. Positive results were obtained in 24/34 (70%) for ER (ER-ICA+) and 22/34 (64%) for PR (PR-ICA+). To evaluate the possible interference of thyroperoxidase in the immunostaining, in consecutive sections of a positive specimen, primary antibody or primary antibody plus bridging antibody or PAP complex was omitted. Using these modified procedures, staining distribution was similar to that obtained by the standard procedure: in contrast, no staining was found in the positive control, i.e. a breast cancer specimen. The inhibition of the endogenous peroxidase caused a loss of staining in both the standard and modified procedures on thyroid specimens; no staining modification was obtained in the positive control. These results suggest that the staining observed in thyroid tissue is not specific and related to the activity of thyroperoxidase on chromogen solution. The complete loss of staining after peroxidase inhibition appears to be in contrast with the results obtained by biochemical method, and different antigenicity of thyroid receptors in comparison with breast receptors may explain this discrepancy.
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PMID:Interference of thyroperoxidase on immuno-cytochemical determination of steroid receptors in thyroid tissue. 844 55

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.
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PMID:Significance of thyroglobulin antibodies cross-reactive with thyroperoxidase (TGPO antibodies) in individual patients and immunized mice. 846 65

The prevalence of circulating autoantibodies against thyroperoxidase (mic-TPO) was determined in 3,000 healthy blood donors (age range: 23 to 60 years) from the Hamburg area. Of the blood donors, 153 (5.1%) were found to have high titer of mic-TPO (> 350 IU/ml). Only two autoantibody positive subjects (0.06%) were chemically hyper- and hypothyroid, respectively. Analysis of HLA-DR specificities revealed that HLA-DR specificities DR3 and DR5 were significantly increased when compared to controls (n = 1,863). Comparison of the autoantibody-positive probands with a group of disease controls, i.e., Graves' patients and patients with lymphocytic thyroiditis, revealed a higher prevalence of HLA-DR3-positive HLA haplotypes in the disease controls when compared to autoantibody positives. Individuals with a mic-TPO level greater than 2,000 IU/ml were almost exclusively found to have one HLA-DR3 or HLA-DR5 positive HLA haplotype. We conclude that a high prevalence of high-titer mic-TPO can be found in healthy blood donors. Circulating signs of thyroid autoimmunity were associated with HLA specificities also found to be associated with autoimmune thyroid diseases.
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PMID:HLA-DR3 and HLA-DR5 confer risk for autoantibody positivity against the thyroperoxidase (mic-TPO) antigen in healthy blood donors. 848 24

We have recently reported that about 50% of papillary thyroid carcinomas harbor an activated TRK or RET oncogene. Two retroviral vectors containing the activated TRK or RET/PTC oncogene have been used to infect a differentiated rat thyroid epithelial cell line, namely the PC Clone 3 cell line. Upon infection with the TRK virus, the PC Clone 3 cells lost only the ability to trap iodide and to express the thyroperoxidase gene. Conversely, when infected with the PTC virus, the PC Clone 3 cells completely lost all of their differentiated functions. However, both the PC-TRK and PC-PTC cell lines were unable to grow in soft agar, and they were not tumorigenic when injected into nude mice. A completely undifferentiated and malignant phenotype was obtained by the cooperation between the TRK or RET and the viral Ha-ras or Ki-ras oncogenes.
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PMID:The TRK and RET tyrosine kinase oncogenes cooperate with ras in the neoplastic transformation of a rat thyroid epithelial cell line. 849 86

Amiodarone has been used in cardiology for more than 20 years as an anti-angina and anti-arrhythmia agent. In the seventies, variations in thyroid hormone and TSH concentrations were described in treated patients. Only recently, however the pathogenic mechanisms leading to dysthyroidism in long-term treatment have been described. Today, the gravity of amiodarone-induced hyperthyroidism has been greatly reduced due to a better understanding of the underlying mechanisms and better surveillance of thyroid function. In clinical practice, the following attitude can be proposed. Thyroid exploration should be completed before prescribing amiodarone: clinical examination should emphasize personal or familial history in search of dysthyroidism or goitre; hormone assays (TSH, free T4) are needed to eliminate any latent thyroid dysfunction, particularly hyperthyroidism with little or no clinical manifestation but sometimes the causal factor in cardiac symptomatology; search for a significant level of anti-thyroperoxidase antibodies can reveal underlying chronic thyroiditis. After prescription, clinical surveillance and TSH assay should be performed at 3 months then every 6 months during treatment. After withdrawal, surveillance should be continued with check-ups at 6 and 12 months.
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PMID:[Effects of amiodarone on thyroid function]. 854 16

Methods for measuring thyroid autoantibodies--to thyroperoxidase (TPOAb), thyroglobulin (TgAb), and thyrotropin receptor (TRAb)--have improved over the last decade, but increasingly, accurate and sensitive methods are needed for identifying patients with autoimmune thyroid diseases and individuals at high risk for onset of thyroid autoimmunity. With the increased quality requirements for these methods, it becomes more important to look at the functional sensitivities and precision profiles of the various methods. International standardization in this field is also needed. Because most sera containing human thyroid autoantibodies display a variety of antigen-specific immunoglobulins of different classes and subclasses with different affinity and avidity in their epitope reaction, investigators must decide whether the autoantibodies should be quantified in terms of immunoglobulin content, antigen/epitope reactivity, or binding capacity. Until these problems are solved, the best means for standardization are the Medical Research Council calibrators for TPOAb and TgAb, whereas no standardization exists for TRAb.
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PMID:Analytical and clinical performance goals for testing autoantibodies to thyroperoxidase, thyroglobulin, and thyrotropin receptor. 856 20

The phosphorylation of thyroid transcription factor-1 (TTF-1), is homeodomain-containing transcription factor that is required for thyroid-specific expression of the thyroglobulin and thyroperoxidase gene promoters, has been studied. Phosphorylation occurs on a maximum of seven serine residues that are distributed in three tryptic peptides. Mutant derivatives of TTF-1, with alanine sites, have been constructed and used to assess the functional relevance of TTF-1 phosphorylation. The DNA binding activity of TTF-1 appears to be phosphorylation-independent, as indicated also by the performance of TTF-1 purified from an overexpressing Escherichia coli strain. Transcriptional activation by TTF-1 could require phosphorylation only in specific cell types since in a co-transfection assay in heterologous cells both wild-type and mutant proteins show a similar transcriptional activity.
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PMID:Mapping and functional role of phosphorylation sites in the thyroid transcription factor-1 (TTF-1). 856 86

We describe a patient with monoclonal gammopathy who subsequently developed thyrotoxicosis, pretibial myxedema and thyroid-associated ophthalmopathy. The pathogenesis of thyrotoxicosis in Graves' disease is due to the presence of autoantibodies that mimic the action of thyrotropin (TSH), called thyroid-stimulating antibodies (TS-ab); these antibodies may or may not inhibit the binding of TSH to the receptor (thyroid-binding inhibiting immunoglobulin, TBII). The patient's immunoglobulins were TS-ab positive and TBII negative when measured on CHO cells expressing the human TSH receptor. The pathogenetic link between the thyroid, orbit and skin is yet to be established but several candidate shared antigens have been proposed, including the TSH receptor itself. The monoclonal immunoglobulins were in evidence before the symptoms of pretibial myxedema, thyrotoxicosis and ophthalmopathy. In addition, the patient had no autoantibodies to thyroglobulin or thyroperoxidase, which are classic markers of thyroid autoimmunity. This combination led us to postulate that the monoclonal gammopathy could be the cause of all the observed pathology. One method to test this hypothesis would be to show that the monoclonal immunoglobulin is a TS-ab. Various methods were used to separate the monoclonal from the polyclonal components of the patient's serum. Preparative isoelectric focusing enabled us to obtain fractions containing only the monoclonal (as revealed by polyacrylamide gel electrophoresis), which were devoid of TS-ab activity (measured as cAMP accumulation in CHO cells expressing the human TSH receptor in a hypotonic bioassay). Subsequently, different oligoclonal fractions were shown to have varying degrees of TS-ab activity, with one fraction having faint biological activity and able to recognize a recombinant TSH receptor preparation in a Western blot. In conclusion, the monoclonal antibody does not seem to be responsible for the thyrotoxicosis, pretibial myxedema and ophthalmopathy. We confirm previous data showing that TSH receptor antibodies in patients with Graves' disease are heterogeneous in nature and we present the first demonstration of autoantibodies capable of binding the TSH receptor but devoid of TBII activity.
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PMID:Patient with monoclonal gammopathy, thyrotoxicosis, pretibial myxedema and thyroid-associated ophthalmopathy; demonstration of direct binding of autoantibodies to the thyrotropin receptor. 859 Sep 66


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