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

T cells from genetically susceptible mice developing experimental autoimmune thyroiditis (EAT) proliferate in response to restimulation with mouse thyroglobulin (MTg) in vitro. The in vitro-activated cells adoptively transfer EAT as well as differentiate into cells cytotoxic for syngeneic thyroid monolayers. To examine the kinetics of T cell subset infiltration and distribution in situ after adoptive transfer, we applied the avidin-biotin-peroxidase labeling technique to thyroid sections, utilizing rat monoclonal antibodies followed by a biotinylated rabbit anti-rat antibody. Female CBA donor mice were immunized with MTg and lipopolysaccharide. Their spleen cells were obtained 7 days later, cultured with MTg, and transferred into recipient mice. The thyroids were removed on Days 7, 10, and 14 after transfer and serially sectioned. The early phase of transferred EAT showed a higher percentage of L3T4+ cells compared to Lyt-2+ cells, yielding a ratio of 2.3 and total T cells of about 35%. By Day 10, both T cell subsets had increased to a total of about 56%. However, the relative increase was greater in the Lyt-2+ subset; the nearly doubled percentage was statistically significant, resulting in a downward shift in the subset ratio to 1.7. Little change in the in situ distribution was seen on Day 14. The percentages of F4/80+ (macrophage) population in lesions examined on Days 10 and 14 were fairly constant and B cell involvement was minimal. These findings illustrate the pathogenic role of both T cell subsets in adoptively transferred EAT and the time-dependent changes in their relative proportions leading to thyroid gland destruction.
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PMID:In situ analysis of T cell subset composition in experimental autoimmune thyroiditis after adoptive transfer of activated spleen cells. 229

This study describes an assay for the detection of cytotoxicity for thyroid cells in serum of patients with autoimmune thyroiditis. Quantitative measurement may be performed by DNA or [3H] leucine incorporation determinations. The cytotoxic effect is localized in the gamma-globulin fraction, and is complement-mediated. It is thyroid specific i.e. it is not observed with fibroblasts and patients with other autoimmune diseases (patients with lupus erythematosis or glomerulonephritis) do not have cytotoxic antibodies directed against thyroid cells. The thyroid cytotoxicity is related to the presence of antimicrosomal antibodies and the effect of circulating antibodies is inhibited by human thyroid peroxidase. These results strengthen the possible implication of circulating antithyroid peroxidase antibodies in thyroid damage observed in autoimmune thyroiditis.
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PMID:Cytotoxic assay of circulating thyroid peroxidase antibodies. 249 49

L3T4+ T cells from genetically susceptible mice developing experimental autoimmune thyroiditis (EAT) were shown earlier to proliferate in response to restimulation with mouse thyroglobulin (MTg) in vitro and to mediate the adoptive transfer of EAT, whereas Lyt-2+ cells differentiated in vitro into cells cytotoxic for thyroid monolayers. Leukocyte suspensions from disrupted thyroid glands examined on Days 13-21 after immunization revealed the accumulation of both T cell subsets in the infiltrate at varying ratios. To characterize the in situ kinetics of cellular infiltration in chronic EAT, we extended the observation intervals after immunization to include Days 21 to 42. The leukocytes in thyroid sections were labeled immunohistochemically first with rat monoclonal antibodies to L3T4, Lyt-2, Thy-1, k light chain, or F4/80 macrophage antigen, then with biotinylated anti-rat IgG, utilizing the avidin-biotin-peroxidase technique. Throughout the 21- to 42-day interval, no significant variations were detected in the percentages of L3T4+ subset, but those of Lyt-2+ cells increased and then declined. The shift in the L3T4+:Lyt-2+ ratio, down from 2.4 to 1.6 and then up to 3.0, was directly related to changes in the Lyt-2+ subpopulation. The F4/80+ and B cell populations changed little during this period. These findings illustrate the changing kinetics of T cell subsets in situ in the development and perpetuation of EAT and MTg-immunized mice.
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PMID:In situ kinetic analysis of thyroid lymphocyte infiltrate in mice developing experimental autoimmune thyroiditis. 257 37

A retrospective study of various benign salivary gland neoplasms was designed to study the frequency distribution and density of immunoglobulins (Igs) located within their various tissue compartments. Buffered-formalin fixed, paraffin embedded sections of Warthin's tumor, cystadenoma, oncocytoma, autoimmune thyroiditis, normal salivary gland, and reactive peripheral lymph node were obtained and processed via the peroxidase-antiperoxidase method following trypsinization to re-expose antigenic sites. The subepithelial and parafollicular zones of Warthin's tumor show an Ig density distribution (IgA greater than or equal to IgG) much greater than IgM, but the relative densities in the germinal center are (IgG = IgM) much greater than IgA. In contrast, the normal salivary gland displays almost exclusively IgA positive cells with only an occasional IgG or IgM positive cell. In general, the three salivary gland neoplasms considered all display a relatively similar frequency distribution with (IgA greater than or equal to IgG) much greater than IgM and much greater densities of all Igs than encountered in the normal salivary gland; however, the densities of IgA and IgG positive cells are greatest in Warthin's tumor. A similar frequency distribution of immunocytes in the parafollicular zone of autoimmune thyroiditis and Warthin's tumor is noted with an increased density of all Igs occurring in autoimmune thyroiditis. A significant increase in the density of IgA immunocytes is noted in the germinal centers of autoimmune thyroiditis. A comparison of Warthin's tumor with a reactive peripheral lymph node shows a marked increase in the density and frequency of IgA in the parafollicular zone in the former lesion, and significant elevations of IgG and IgM in the latter process both in the parafollicular zone and in the germinal centers. No data generated by this study support an autoimmune etiology of Warthin's tumor. Histopathologically, the oncocytoma appears to represent a pathologic entity distinctly different from papillary cystadenoma lymphomatosum. Our data tend to support the hypothesis that Warthin's tumor arises within ectopic salivary gland elements trapped within paraparotid or intraparotid lymph nodes during embryogenesis. The cystadenoma appears to represent a similar pathologic process arising in salivary gland elements independent of lymphoid tissue.
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PMID:Immunohistopathology of papillary cystadenoma lymphomatosum (Warthin's tumor). 636 53

The peroxidase-antiperoxidase (PAP) staining method was used to identify immunoglobulin-containing cells in the lymphoid infiltrates of thyroids removed from patients with Hashimoto's autoimmune thyroiditis. A composite picture of the distribution of such cells in the thyroid infiltrate was obtained by carefully superimposing cell-distribution maps from serial histological sections, each stained for a different immunoglobulin class. Ig-containing cells were present to varying extents in all areas of the gland, but were most dense in areas of epithelial 'invasion'. IgG was the commonest immunoglobulin, but there were more cells containing IgD and IgE than IgA or IgM. Both lambda and K light chains were identified in cells occupying the follicle centres. Lymphoid follicle structure was strikingly similar to that described previously for gut-associated lymphoid tissue (GALT), and the theory is advanced that autoimmune thyroiditis represents a form of ectopic GALT in which B-cells, which normally home on markers in the gut, are attracted instead to antigenically active sites in the thyroid.
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PMID:The distribution of immunoglobulin-containing cells in human autoimmune thyroiditis. 638 96

Thyroid peroxidase (TPO), a cell surface glycoprotein, is the major autoantigen in autoimmune thyroiditis in humans. The molecular cloning and expression of Ig genes from thyroid-infiltrating B cells has generated a large repertoire of human TPO Fab that have been used to map an immunodominant region on TPO. However, the topological site of this region, consisting of a cluster of highly conformational epitopes, remains unknown. Using the recently elucidated three-dimensional structure of myeloperoxidase as a model, we stably expressed on the surface of eukaryotic cells eight "guided" mutants of the TPO molecule. The sites of these mutations were strategically located to alter the surface contour of the molecule with minimal disruption to its core structure. Remarkably, in the present study (in contrast to previous unguided TPO mutagenesis studies), all eight TPO mutants retained recognition by the TPO Fab. These results support the validity of the model used for mutagenesis. Although not identifying the immunodominant region on TPO in thyroid autoimmunity, our data provide evidence against the involvement of certain topological segments and may help to narrow the search for this region. The most open region remaining as a candidate location is the antero-inferior portion of the molecule.
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PMID:The quest for the autoantibody immunodominant region on thyroid peroxidase: guided mutagenesis based on a hypothetical three-dimensional model. 860 66

Previously, we have shown that it is possible to induce, in naive mice, systemic autoimmune diseases (e.g., antiphospholipid syndrome and systemic lupus erythematosus) by idiotypic manipulation. In the present study we expanded our experience to examine whether idiotypic manipulation could be utilized to induce organ-specific autoantibodies and a disease mediated by cellular mechanisms, namely, experimental autoimmune thyroiditis. Fifteen BALB/c mice were immunized with a monoclonal mouse anti-human thyroglobulin (hTg) antibody; controls were immunized with an irrelevant mouse IgG. The mice immunized with anti-hTg antibody developed, 6 weeks after immunization, autoantibodies to human thyroglobulin, but not to dsDNA, cardiolipin, or myeloperoxidase. The presence of specific autoantibodies was associated with low production of thyroid hormones, and during a follow-up of 20 weeks the mice did not develop characteristic histological signs of thyroiditis. We conclude that idiotypic manipulation can induce anti-thyroglobulin autoantibodies.
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PMID:Induction of thyroid autoantibodies in naive mice by idiotypic manipulation. 862 60

We report here a 15-year-old girl with myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated crescentic glomerulonephritis (CreGN) and subclinical autoimmune thyroiditis. She was found to have proteinuria and hematuria by a school mass-screening a year before the first visit to the hospital, where a routine examination revealed blood urea nitrogen (BUN) 36.8 mg/dl and serum creatinine concentration of 1.63 mg/dl, although she had no apparent disabilities. On admission, the additional laboratory findings showed proteinuria of 1.06 g/day, hematuria of 3+, and a creatinine clearance of 30.1 ml/min. Hypocomplementemia was not observed. A renal biopsy revealed pauci-immune CreGN with 95% fibrocellular crescents, 84% sclerosis and/or hyalinosis and a massive cellular infiltration in the interstitium. She had MPO-ANCA of 865 EU/ml and an anti-thyroid microsome antibody titer of 1:1,600 without the detection of anti-glomerular basement membrane antibodies. Laboratory tests and scintigraphies for the thyroid gland did not show any abnormalities. Under the diagnosis of MPO-ANCA-associated CreGN, cocktail therapy consisting of prednisolone, cyclophosphamide, dilazep hydrochloride and warfarin was started. Improvement of urinary abnormalities and suppression of further deterioration of renal function were observed. Serial renal biopsy 6 months after the initiation of therapy showed decrement of interstitial cell infiltration and no generation of other crescentic glomeruli. The patient's serum titer of anti-thyroid microsome antibody was not affected by the adsorption of MPO-reacted IgG, suggesting that MPO-ANCA was not cross-reactive to thyroid microsome antigen.
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PMID:An adolescent case of anti-neutrophil cytoplasmic autoantibodies-associated crescentic glomerulonephritis complicated with subclinical autoimmune thyroiditis. 894 Aug 29

Asymptomatic chronic thyroiditis (ACT) is a variant of the autoimmune thyroiditis characterized by the presence of circulating anti-thyroid antibodies and the absence of palpable goiter. Thyroid function can be normal but a considerable percentage of ACT patients tend to develop subclinical hypothyroidism over time and thus periodical controls of thyroid hormones and TSH levels are needed. At present, useful parameters for predicting the functional outcome of ACT patients are lacking. To investigate this aspect, we evaluated 57 consecutive ACT patients (51 females, 6 males, aged 22-56 years) by means of thyroid 99mTc-pertechnetate scintigraphy and echography, and by measuring the serum level of anti-peroxidase antibodies (TPOAbs), FT4, T3 and TSH. At first observation, 30 patients were euthyroid whereas 27 had subclinical hypothyroidism. No patient had been previously treated with thyroid hormones. Thyroid scan showed a normal pattern or a diffuse and mild irregular uptake, without differences between euthyroid and subclinical hypothyroid patients. TPOAb levels tend to be higher in patients with subclinical hypothyroidism in comparison to the euthyroid patients (5893 +/- 1423 and 3943 +/- 912 UI/mL, respectively) but the difference was not statistically significant by using Student's "t"-test. Echography showed a normal pattern in 14 patients, while a diffuse hypoechoic pattern in the other cases, mild in 12, moderate in 19 and marked in 12, was found. A significantly higher prevalence of subclinical hypothyroidism was observed in the group of patients with a moderate or marked hypoechoic pattern in comparison to the group with a normo-echoic or mild hypoechoic pattern (70.4% versus 23.0%, Fisher's exact test p = 0.00003). Furthermore, the 3 patients who developed thyroid failure during a one-year follow-up also presented a moderate or marked hypoechoic pattern. Our data suggest that the echo-pattern can be a useful predictor of thyroid failure in ACT patients and thus the echographic evaluation should be included in the diagnostic protocol of these patients.
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PMID:Functional meaning of scintigraphic and echographic patterns, and of circulating anti-peroxidase antibodies in asymptomatic chronic thyroiditis. 905 Mar 41


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