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:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is evidence to suggest that elevated levels of iodide in the diet are associated with autoimmune thyroid disease (ATD) in susceptible individuals, and that autoimmune thyroiditis (Hashimoto's disease) is less common in susceptible individuals who live in regions with dietary iodine deficiency. There are epidemiologic studies in endemic goiter areas that report an increase in ATD, particularly thyroiditis, after the therapeutic administration of iodized salt, bread and oil. Lymphocytic infiltration of the thyroid is rarely found in patients from severe endemic goiter regions, yet there is a reversal of this observation after dietary iodine supplementation. Thyroid antibodies, both thyroglobulin (TgAb) and peroxidase (TpAb) or microsomal, were not detected in serum from patients with endemic goiter, but became positive in 43% of subjects three and six months after therapy with iodized oil, and there developed transient hyperthyroidism. Similarly, the addition of iodine to the diet or the administration of iodine-containing medications increases the frequency of ATD and the severity of existing autoimmune thyroiditis. Furthermore, autoimmune thyroiditis has been induced by the administration of excess iodide to strains of chickens and rats that are genetically predetermined to develop the disease. We are beginning to understand the pathogenesis of ATD. In hyperthyroidism the evidence clearly supports the hypothesis that TSH receptor antibodies (TRAb) stimulate the TSH receptor to induce excessive and sustained secretion of thyroid hormones. Cellmediated immune mechanisms, such as antibody dependent cellmediated cytotoxicity (ADCC), initiate the lymphocytic infiltration and thyrocytotoxicity in autoimmune thyroiditis. The mechanisms that initiate the development of the abnormal immune response and the relationship of ATD with excess iodide are poorly understood. There is evidence that an increase in the iodination of thyroglobulin (Tg) enhances its immunogenicity. The results of clinical and experimental studies support the requirement of a genetic predisposition to the development of ATD that may be precipitated by exposure to certain environmental factors. Another mechanism supported by experimental data is the direct toxic effect of excess iodide on iodide-deficient thyroid glands. High concentrations of iodide after oxidation to iodine causes epithelial necrosis and inflammation associated with lipofuscin accumulation suggestive of toxicity mediated by lipid peroxidation from excessive amounts of free radicals. The epithelial damage would initiate inflammatory and immune responses. Although these mechanisms would relate to the onset of autoimmune thyroiditis on exposure to excessive amounts of iodide, the relationship of iodide intake and autoimmune hyperthyroidism is less clear.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The relationship between autoimmune thyroid disease and iodine intake: a review. 134 85

Recently described immunological functions for heat shock proteins (HSPs) and our previous demonstration of site-selective HSP-72 expression in cultured fibroblasts derived from extrathyroidal manifestations of Graves' disease (GD) prompted us to determine whether expression of the inducible 72-kilodalton HSP can be detected in human thyroid tissues. Immunohistochemistry was performed on formalin-fixed paraffin-embedded thyroid tissue specimens from patients with GD, Hashimoto's thyroiditis (HD), and multinodular goiter (MNG) as well as on normal thyroid tissue. A mouse monoclonal anti-HSP-72 antibody and an ultrasensitive avidin-biotin-peroxidase complex detection system were used for these studies. Striking differences in HSP-72 immunoreactivity were detected both between tissues from GD and HD compared with MNG and normal thyroid and between GD thyroid glands treated preoperatively with antithyroid medication and untreated GD glands. Strong HSP-72 reactivity in GD and HD tissues was detected in thyroid follicles as well lymphocytic infiltrates. No HSP-72 reactivity was detected in MNG or normal thyroid tissue. HSP-72 immunoreactivity was markedly reduced in GD glands that received preoperative antithyroid drug treatment. In conclusion, high levels of HSP-72 expression in autoimmune thyroid disease may reflect a state of chronic cellular stress, but could also represent an immunomodulatory factor of relevance in the autoimmune process in GD.
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PMID:Immunohistochemical detection and localization of a 72-kilodalton heat shock protein in autoimmune thyroid disease. 154 33

This paper describes the use of an ELISA technique to assess the involvement of the complement system in the pathogenesis of autoimmune thyroid disease (AITD). Microtitre plates coated with thyroid membrane antigen were exposed to serum samples obtained from AITD patients, all of whom showed elevated levels of circulating anti-thyroid autoantibodies, and dilute guinea pig serum, as a source of complement, was then added to the microtitre wells. The degree of activation of the classical complement pathway was assessed by measuring the bound complement component C3 using a peroxidase conjugated anti-guinea pig C3 antiserum. C3 fixation and activation was greater in the presence of serum from patients with Hashimoto's disease when compared with that seen in patients with autoimmune hyperthyroidism (Graves' disease). Serum samples obtained from normal healthy volunteers and from patients with thyroid neoplasia were negative in this assay. The method allows the calculation of a putative "biologically active autoantibody" level and analysis of these data confirm our earlier observation that the species of autoantibody found in autoimmune hypothyroidism are potentially more destructive than those found in other forms of AITD.
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PMID:Elisa for the measurement of complement C3 activation by autoantibodies directed against thyroid membrane antigens. 166 67

Cloned cDNA templates of thyroid peroxidase (TPO) have been used in conjunction with the polymerase chain reaction (PCR) to express selected segments of the thyroid microsomal/peroxidase antigen (TMA/TPO) as recombinant protein in E. coli. Six small, different recombinant fragments averaging 120 amino acid residues and one large fragment (269 amino acids) of TPO which together encompass 80% of the extracellular region of the molecule have been produced and autoantibody (aAb) binding sites analysed by immunoblotting. A minimum of six independent, sequential antigenic determinants have been localized on the recombinant proteins and these map to the amino terminal, the central core region and the carboxyl terminal of the TPO molecule. More accurately, the six antigenic sites reside on overlapping recombinant TPO preparations termed R1a + R1b (residues 1 to 160) R1c (residues 145 to 250), R2b (residues 457 to 589), R3a (residues 577-677), R3b (residues 657-767) and R3c (residues 737-845). The large fragment of TPO termed R3 (residues 577-845) encompassing R3a, R3b and R3c also reacts with the aAbs. Different sera from patients with autoimmune thyroid disease contain antibodies to TMA/TPO which differ in their fine specificity. The use of recombinant molecular biological techniques together with PCR to prepare small segments of a large autoantigen as recombinant protein will now allow studies to progress on autoepitope mapping of the precise amino acid sequences of the TPO molecule with the use of synthetic peptides.
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PMID:Mapping of autoantigenic epitopes on recombinant thyroid peroxidase fragments using the polymerase chain reaction. 171 75

Islet cell antibodies (ICAs) were assayed in 316 patients with autoimmune thyroid disease (AITD; 190 with Graves' disease, 126 with Hashimoto's thyroiditis), 53 patients with insulin-dependent diabetes mellitus (IDDM), and 144 healthy control subjects. ICAs were measured by an immunohistochemical method with peroxidase-labeled protein A and human pancreatic tissues. The prevalence of ICAs in patients with AITD was 7.6% (24 of 316), whereas the prevalence in control subjects was 0.7% (1 of 144). Among 24 ICA+ patients, 20 (83%) had IDDM. In these 20 patients, the duration of diabetes from clinical onset was 5.4 +/- 5.1 yr. ICAs in patients with IDDM alone were positive in 90.9% at 1 yr and 7.7% at 5 yr after the onset of diabetes. These data have shown that most ICA+ patients with AITD have IDDM and that the prevalence of ICAs in patients with AITD in Japanese is as high as that found among whites, whereas the incidence of IDDM in Japanese is approximately one-thirtieth or one-fiftieth of that in whites.
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PMID:Islet cell antibodies in patients with autoimmune thyroid disease. 199 72

Thyroid peroxidase is a heme-containing, membrane-bound, glycoprotein enzyme that catalyzes iodination and coupling in the thyroid gland. It is also the antigen for microsomal autoantibodies that are commonly found in the serum of patients with autoimmune thyroid disease. We examined the effect of deglycosylation on the catalytic functions and the immunoreactivity of this enzyme. A highly purified, solubilized, large tryptic fragment of porcine thyroid peroxidase, retaining all of the N-linked glycosylation sites of the native enzyme and displaying full catalytic activity was used. It was deglycosylated by treatment with N-glycanase under nondenaturing conditions. The loss in relative molecular mass after treatment, determined by gel electrophoresis, was about 75% of the estimated molecular weight of the glycan portion of porcine thyroid peroxidase. Lectin blots performed with horseradish peroxidase-conjugated concanavalin A showed a similar loss in relative molecular mass but some residual carbohydrate. The intensity of the carbohydrate stain was consistent with the loss of about 75% of the glycans. Despite this loss, three different assays for catalytic activity of porcine thyroid peroxidase were not significantly decreased. Immunoreactivity measured by immunoblotting and by enzyme-linked immunosorbent assay was also unimpaired. These findings suggest that N-glycanase-sensitive glycans in porcine thyroid peroxidase do not act as antigenic determinants and play a minor role, if any, in catalytic activity and, presumably therefore, in the maintenance of protein conformation.
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PMID:Enzymatic deglycosylation of porcine thyroid peroxidase: effects on catalytic activity and immunoreactivity. 200 Jun 95

Different phenomena under consideration, lymphocytic and macrophagic infiltration and increased thyrocyte class I and class II antigen expression, normally ascribed to autoimmune thyroid disease (Graves' disease; Hashimoto's thyroiditis) were frequently found in thyroid glands with autonomous nodules, too. Contrary, nodular formations in the vast majority of nodular goiters were not associated with these immunopathological findings. Furthermore, thyroid microsomal, anti-peroxidase and TSH-receptor antibodies although at low frequency rates, were only detected in cases of autonomous nodules but not in cases of nodular goiters. From these findings we conclude that the immune phenomenon observed in thyroid autonomy could not be a consequence of nodular formations but that at least in some cases of thyroid autonomy immunopathogenic mechanisms may play an important role. Based on the fact that class I hyper-expression was more common and that a stronger correlation of cell infiltration with increased class I than with increased class II expression on thyrocytes existed we propose, that if the initial event of the autoimmune process is indeed increased class II expression, this stimulus may more likely originate from increased non-thyrocyte class II positivity (for example dendritic or endothelial cells) than from thyrocyte class II positivity. But, if aberrant class II expression is not the initial stimulus, another candidate could be the increased thyrocyte class I expression observed, probably due to the action of interferon alpha and/or beta induced by any unknown stimulus (viruses?).
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PMID:Immunopathological findings and thyroid autoantibodies in thyroid autonomy. 220 77

The recent cloning of the thyroid peroxidase (TPO) has shown that it is identical to the thyroid microsomal antigen (TMA), a potent antigen involved in autoimmune thyroid disease (ATD), which shares significant sequence homology with myeloperoxidase. The present study shows that autoantibodies (aAb) to the TMA/TPO antigen cross-react with human leucocyte myeloperoxidase, bovine lactoperoxidase and horseradish peroxidase. Cross-reactivity to myeloperoxidase was only apparent by ELISA using reduced and alkylated antigen preparations or by immunoblotting following denaturation with SDS. Sequential absorption of sera on SDS-denatured thyroid microsomes immobilized on Sepharose-4B followed by absorption on native microsomes removed all aAb specificities to TMA/TPO and the three peroxidase preparations, giving compelling evidence on the genuine cross-reactive nature of these aAbs. Sera from different patients contain different qualitative and quantitative specificities of aAb to the TMA/TPO antigen, confirming the polyclonal nature of this autoimmune response.
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PMID:Thyroid microsomal/thyroid peroxidase autoantibodies show discrete patterns of cross-reactivity to myeloperoxidase, lactoperoxidase and horseradish peroxidase. 254 81

An expression plasmid containing both human thyroid peroxidase and mouse dihydrofolate reductase cDNAs was transfected into chinese hamster ovary cells. The stably transformed cells constitutively expressed immunoreactive thyroid peroxidase on the cell surface. These cells were further used to establish a subline producing a large amount of thyroid peroxidase by selecting clones resistant to methotrexate. The molecular weight of the expressed thyroid peroxidase was the same as purified human thyroid peroxidase. This expressed protein had peroxidase activity when determined by guaiacol oxidation. Furthermore, the expressed thyroid peroxidase was immunoreactive to sera of patients with autoimmune thyroid disease in which autoantibodies to thyroid peroxidase appeared.
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PMID:Stable high level expression of human thyroid peroxidase in cultured Chinese hamster ovary cells. 259 Feb 1

In vitro production of antithyroid microsomal antibody (AMA) and antithyroid peroxidase antibody (APA) by peripheral blood lymphocytes from patients with autoimmune thyroid disease (AITD) has been studied and compared, in view of the evidence for identity of the two differently measured antibodies. Peripheral non-T cells (2 x 10(5)) and autologous CD4 (helper/inducer) cells (2 x 10(5)) from patients with positive serum AMA were cultured for 7 days with pokeweed mitogen (PWM). B cells secreting AMA or APA were detected by the enzyme-linked immunosorbent assay (ELISA) spot assay. AMA or APA in the culture supernatants of these cells was also measured by ELISA. There was a significant correlation between the number of AMA- (IgG class) secreting cells and APA- (IgG class) secreting cells (r = 0.89 p less than 0.001). There was also a significant correlation between AMA- and APA-ELISA indices (r = 0.86, p less than 0.001). Furthermore, the number of AMA- or APA-secreting cells significantly correlated with AMA or APA secreted in the culture supernatants (r = 0.91, r = 0.92), respectively. These data show that peripheral blood lymphocytes from patients with AITD were able to produce antibodies against thyroid peroxidase (TPO) in vitro, as well as antibodies against thyroid microsomal antigen, after PWM stimulation. The significant correlation between in vitro AMA versus APA production, or the number of AMA- versus APA-secreting cells, accords with the evidence that TPO is identical to, or at least the major antigenic protein component of, thyroid microsomal antigen.
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PMID:Comparison of measurements of in vitro production of antithyroid microsomal antibody versus antithyroid peroxidase antibody. 285 41


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