Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004364 (autoimmune disease)
 24,845 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A detailed examination of the epitopes recognized by autoantibodies (aAbs) to the thyroid microsomal antigen/thyroid peroxidase (TMA/TPO) in patients with thyroid autoimmune disease has been made using a combination of immunochemical and enzymatic techniques. Our results demonstrate the the autoimmune response to thyroid microsomal antigen/thyroid peroxidase (TMA/TPO) is multifocal and far more heterogeneous than hitherto recognized. By immunoblotting with aAbs, antigenic determinants on the TMA/TPO have been recognized that are either susceptible to polypeptide denaturation and/or sensitive to the effects of reducing agents. Furthermore, these aAbs can inhibit, to varying degrees, the enzymatic activity of solubilized preparations of TPO in microsomes, as ascertained by peroxidation of guaiacol and iodide. A large proportion of the autoimmune response is directed to the guaiacol peroxidation site. The data support the view that the autoimmune reactivity to the TMA/TPO is a specific polyclonal response with a minimum of six distinct, independent determinants that are recognized by aAbs.
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PMID:Autoantibodies to the thyroid microsomal/thyroid peroxidase antigen are polyclonal and directed to several distinct antigenic sites. 245 86

We have reviewed the impact of cellular and molecular biology on our understanding of the immune system and thyroid autoimmune disease and presented the evidence that MHC, TCR and immunoglobulin genes are involved in susceptibility to such disease. At the level of the target thyroid epithelial cell, the identification of the genes for Tg and TPO (the microsomal antigen) using recombinant DNA techniques are evidence of dramatic progress. On the humoral side of the immune response, the investigation of restricted clonality is still hampered by the technical difficulties in obtaining immortal B cell lines producing thyroid antigen specific high affinity IgG antibodies, although the advent of tools to sequence the immunoglobulin V genes from small quantities of DNA will overcome this difficulty (e.g. by polymerase chain reactions). T cells have also begun to be characterized both phenotypically, thanks to the advent of ever better characterized monoclonal antibodies, and functionally at the clonal level, thanks to refinement of cell culture techniques. Future studies in this area will also need to focus on cell immortalization and maintenance of antigen-specific responses although, major strides in the direct sequencing of the TCR are taking place and investigation of T cell receptors in antigen-specific T cells should be feasible. MHC associations with thyroid autoimmune disease, as studied by analysis of RFLP patterns, have not significantly improved already established serological HLA associations and direct MHC gene sequencing will be required. Analysis of the organ-specific regulation of MHC class II gene expression has led to a better understanding of the functional role of MHC class II genes in thyroid autoimmune disease at the target cell level. Such studies have pointed out important local immune responses within the thyroid gland but have not yet provided the initiating factor or factors for human autoimmune thyroid disease in genetically susceptible individuals.
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PMID:Human autoimmune thyroid disease: cellular and molecular aspects. 307 47

The aim of this study is to determine whether antithyroid drugs (ATD) act via inhibiting thyroid hormone synthesis or by interfering with the immune process which leads to autoimmune disease. Previously we had demonstrated that ATD do not affect HLA-DR and TPO antigen expressions induced by appropriate stimulus in normal thyrocytes, so we decided to study what happens when the same experiments are performed using autoimmune thyrocytes. Cultured thyroid tissue from patients operated on for Graves' Disease or Hashimoto's Thyroiditis were stimulated with TSH or TBII alone or associated with ATD; TPO antigen expression was evaluated by the Cytotoxicity Assay using human monoclonal antiTPO. When autoimmune thyrocytes were cultured and no stimulus was used or with the addition of MMI or PTU alone, very low values of TPO expression were noted (8.6 +/- 6.7, 5.0 +/- 7.1 and 4.2% +/- 2.3% respectively); if they were stimulated with TSH or TBII, a sharp rise of TPO antigen expression was detected (54.4 +/- 23.3 and 62.6 +/- 16.5%), these figures being significantly different from unstimulated cells (p < 0.001). If both stimulus were used associated with ATD, the high TPO antigen expression was unaffected. It is concluded that, at least in vitro, ATD have no effect upon induced-antigen expression in autoimmune thyrocytes. Since they do not alter antigen presentation, a primary step in the immune process, it is difficult to accept that their mechanism of action is through interference with the immune response.
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PMID:[Lack of in vitro effect of antithyroid drugs upon peroxidase antigen expression in autoimmune thyroid disease]. 751 5

This chapter has outlined the complex process required for thyroid growth and function. Both events are regulated by TSHR via a multiplicity of signals, with the aid of and requirement for a multiplicity of hormones that regulate the TSHR via receptor cross-talk: insulin, IGF-I, adrenergic receptors, and purinergic receptors. Cross-talk appears to regulate G-protein interactions or activities induced by TSH as well as TSHR gene expression. The TSHR structure and its mechanism of signal transduction is being rapidly unraveled in several laboratories, since the recent cloning of the receptor. In addition, the epitopes for autoantibodies against the receptor that can subvert the normal regulated synthesis and secretion of thyroid hormones, causing hyper- or hypofunction, have been defined. Studies of regulation of the TSHR minimal promotor have uncovered a better understanding of the mechanisms by which TSH regulates both growth and function of the thyroid cell. A key novel component of this phenomenon involves TSH AMP positive and negative regulation of the TSHR. Negative transcriptional regulation is a common feature of MHC class I genes in the thyroid. Subversion of negative regulation or too little negative regulation is suggested to result in autoimmune disease. Methimazole and iodide at autoregulatory levels may be important in reversing this process and returning thyroid function to normal. Their action appears to involve factors that react with the IREs on both the TSHR and the TG promoter. Too much negative regulation, as in the case of ras transformation, results in abnormal growth without function. TTF-1 is implicated as a critical autoregulatory component in both positive and negative regulation of the TSHR and appears to be the link between TSH, the TSHR, TSHR-mediated signals, TG and TPO biosynthesis, and thyroid hormone formation. Differentially regulated expression of the TSHR and TG by cAMP and insulin depend on differences in the specificity of the TTF-1 site, that is, the lack of Pax-8 interactions with the TSHR, and the IRE sites. Single-strand binding proteins will become important in determining how TSHR transcription is controlled mechanistically.
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PMID:The thyrotropin receptor. 770 2

Hashimoto disease is a representative organ-specific autoimmune disease. It occurs very frequently in middle-aged women. Generally, the symptom is only diffuse and elastic hard goiters detected by careful plpation. Immunological tests frequently reveal anti-thyroglobulin antibody and anti-TPO antibody. Hypothyroidism develops in some patient along with progression of the disease. In some patient, on the other hand, a condition called destructive thyroiditis may develop during the course of the disease, in which the thyroid gland is transiently destroyed, accompanied by thyrotoxic state. In this state, namely painless thyroiditis, 123I-uptake ratio is extremely low and TSH-receptor antibody is generally not observed. The thyroid hormone is administered to patient with large goiter or hypothyroidism, and antiphlogistic analgesics or adrenocortical hormone with beta-blockers in case of destructive thyroiditis.
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PMID:[Hashimoto disease]. 1048 44

Type 1 diabetes mellitus is an autoimmune disease in which the presence of different autoantigens can often be found. The aim of our study was to evaluate the prevalence of antibodies against insulin (IA) and autoantibodies against glutamic acid decarboxylase (anti-GAD), tyrosine phosphatase IA-2 (anti-IA-2), thyroid microsomal peroxidase (anti-TPO) and thyroglobulin (anti-TG) in 55 randomly selected Type 1 diabetic patients (34 males, 21 females). Mean age of these patients was 39 +/- 12 yrs, mean duration of diabetes 18 +/- 13 yrs. Positivity of anti-GAD was found in 29 (58%) patients, anti-IA-2 in 13 (25%) patients, IA in 46 (85%) patients, anti-TPO in 10 (21%) and anti-TG in 11 (23%) patients. Simultaneous positivity of thyroid and islet autoantibodies was found in 6 (11%) patients whereas the positivity at least one of them was in 38 (69%) patients. No relationship between glycated hemoglobin and autoantibody concentration was found in the whole group of patients. The autoimmune thyroid disease was newly detected in 4 patients from high concentration of thyroid autoantibodies together with impaired TSH and T4 values and ultrasonography finding. No clinical evidence of thyroid disease was previously found in these patients. Positivity of anti-GAD or anti-IA-2 was found in almost 65% and of any thyroid autoantibody in almost 30% of our patients. Four patients with autoimmune thyroid disease were newly identified. We conclude that the evaluation of thyroid autoantibodies in Type 1 diabetic patients may improve the diagnosis of thyroid disease in very early stage and thus prevent consequent complications.
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PMID:The evaluation of thyroid and islet autoantibodies in type 1 diabetes mellitus. 1122 67

It has been shown that TSH upregulates rat NIS gene expression in vitro, and this induction can be modulated by cytokines. Analysis of the distribution of rat NIS mRNA ex vivo demonstrated variable levels of NIS transcription in different tissue samples. - IL-1beta and IL-6 have been found to decrease NIS mRNA expression in TSH-stimulated FRTL-5-cells. IL-6 has no effect on NIS functional activity, whereas IL-1beta suppresses iodide accumulation. The NIS is expressed in thyroid tissue of patients with autoimmune thyroid diseases, and its expression is increased in Graves' disease. With respect to other thyroidal autoantigens such as TPO and Tg, NIS obviously shows a very similar pattern to the well-described antigenic targets and may participate as an autoantigen in these diseases. Up to now only data of in vitro studies are available which started to evaluate the effects of different cytokines on NIS expression. The mechanisms of NIS regulation with respect to cytokine modulation in thyroid autoimmune disease remain still unproven and data of experimental in vivo studies and clinical trials in patients with thyroid autoimmune disease have to further elucidate these open questions in the future.
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PMID:Sodium/iodide symporter (NIS) and cytokines. 1157 36

Cortisol and prolactin, which are considered to have an immunomodulatory effect, and selected autoantibodies were determined in Hashimoto's thyroiditis. 37 patients (8 males and 29 females) (54 +/- 13.8 years) and an equal number of sex- and age-matched normal subjects (52.6 +/- 14.2 years) were studied. None of the 74 subjects suffered from any other immunological, infectious, hepatic, renal or malignant diseases. Patients with Hashimoto's thyroiditis exhibited significantly higher (p < 0.016) prolactin values (14.0 +/- 3.8 ng/ml) than did control subjects (6.5 +/- 1.3 ng/ml). In contrast, cortisol levels were lower in Hashimoto's thyroiditis (13.5 +/- 3.2 microg/dl) vs. normal state (16.0 +/- 1.13 microg/dl), (p < 0.05). The prevalence of anti-TPO and anti-Tg antibodies was 100 % and 43 % in the patients with Hashimoto's disease. In contrast, no subject of the control group was positive for anti-TPO, although 9 subjects (24 %) were positive for anti-Tg autoantibodies. The percentage of positive autoantibodies to nucleus, smooth-muscle, and parietal cells in the patients (36.0, 10.9 and 18.5 %, respectively) was higher than that in healthy group (11.0 and 0 % respectively). Notably, neither group was positive for antibodies against double-stranded DNA or mitochondria. In conclusion, our results provide evidence for a polyclonal activity in Hashimoto's thyroiditis, an organ-specific autoimmune disease, associated with an altered prolactin-adrenocortical status. Such information should initiate longitudinal studies to clarify the exact time sequence of these events related to the disease's activity.
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PMID:Elevated prolactin to cortisol ratio and polyclonal autoimmune activation in Hashimoto's thyroiditis. 1160 77

The use of highly sensitive immunometric methods in clinical laboratories to assay anti-thyroid antibodies has progressively expanded in recent years but it is not known whether the new techniques have improved the analytical variability connected with the preceding methodologies. The Italian Society of Laboratory Medicine Study Group on Autoimmune Diseases conducted a collaborative study with the biomedical industry to evaluate the degree of standardization of the new analytical procedures. Twelve companies agreed to participate in the study on the search for anti-thyroglobulin (anti-Tg) and anti-thyroperoxidase (anti-TPO) antibodies in nine sera from patients with autoimmune thyroiditis, and in six sera from patients with non-autoimmune thyroid disease; ten immunometric and three immunofluorescence methods were employed. Agreement of qualitative results was close to 90% for anti-Tg and 97% for anti-TPO, with no important differences between the methods; variability of the quantitative results, expressed as CV% of absolute (in lU/ml) and relative (in cut-off concentration multiples) values was 93.9% and 102.3%, respectively, for anti-Tg, and 75.5% and 62.9%, respectively, for anti-TPO. These findings show that despite the progressive improvement in the analytical techniques, the variability between methods for the assay of anti-Tg and anti-TPO is still unexpectedly high, and probably due to several factors such as uncertainty in defining the positive cutoff concentration, absence of adequate international reference preparations, modality of autoantigen purification, and analytical variability in the assay procedures.
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PMID:Immunoassay of anti-thyroid autoantibodies: high analytical variability in second generation methods. 1221 50

The patient is a 71-year-old woman who underwent splenectomy after the diagnosis of idiopathic portal hypertension (IPH) at the age of 51 years. Thirst and polyuria occurred in December 1995. In April 1996, she was hospitalized for assessment because of elevation of her blood glucose and HbA1c levels to 535 mg/dl and 14.9%, respectively. The GAD antibody level was high (256 units/ml) and tests for ICA and anti-TPO antibody were positive. Since her HLA type was A 24, B 13, B 46, CW 1, CW 3, DRB 1*[0901/0901], DQB 1*[0303/0303], and DPB 1*[0201/0201], this patient was regarded as being susceptible to type 1 diabetes mellitus. There was no evidence of portal hypertension at the time of consultation. Although there was a considerable difference in the time of onset between IPH and type I diabetes mellitus, we reported this patient as a valuable case for investigating the complications of autoimmune disease.
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PMID:[A case of type 1 diabetes mellitus in an elderly patient with a history of idiopathic portal hypertension]. 1268 17


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