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1.
The autoimmune thyroid diseases (AITD) include Graves' disease (GD) and Hashimoto's thyroiditis (HT), which are characterised by a breakdown in immune tolerance to thyroid antigens. Unravelling the genetic architecture of AITD is vital to better understanding of AITD pathogenesis, required to advance therapeutic options in both disease management and prevention. The early whole-genome linkage and candidate gene association studies provided the first evidence that the HLA region and CTLA-4 represented AITD risk loci. Recent improvements in; high throughput genotyping technologies, collection of larger disease cohorts and cataloguing of genome-scale variation have facilitated genome-wide association studies and more thorough screening of candidate gene regions. This has allowed identification of many novel AITD risk genes and more detailed association mapping. The growing number of confirmed AITD susceptibility loci, implicates a number of putative disease mechanisms most of which are tightly linked with aspects of immune system function. The unprecedented advances in genetic study will allow future studies to identify further novel disease risk genes and to identify aetiological variants within specific gene regions, which will undoubtedly lead to a better understanding of AITD patho-physiology.  相似文献   

2.
We investigated the response to immunoglobulin G-secreting cells (ISC) by peripheral blood mononuclear cells (PB-MNC) and purified B cells following stimulation with Staphylococcus aureus Cowan 1 (SAC) or with B cell stimulatory factor 2 (interleukin 6: IL-6), using the reverse hemolytic plaque assay in an attempt to clarify the immunological functions of peripheral blood B cells in patients with autoimmune thyroid disease (AITD). ISC response by PB-MNC following stimulation with SAC was significantly decreased in patients in the hyperthyroid state of Graves' disease and Hashimoto's thyroiditis as compared with that of normal controls. The difference in SAC-response was not significant between patients with euthyroid state of Graves' disease and normal controls. ISC response by PB-MNC following stimulation with SAC exhibited a reciprocal relationship to TRAb in patients with Graves' disease. Using purified B cells, some spontaneous ISC response without SAC stimulation was observed in patients in the hyperthyroid state of Graves' disease and Hashimoto's thyroiditis. This spontaneous ISC response was further enhanced by IL-6. These results suggest that in organ-specific autoimmune diseases such as AITD, immunological abnormalities exist in B cells and some B cells are nonspecifically activated in the immunologically active state.  相似文献   

3.
Antimicrosomal antibodies are present in the sera of most patients with autoimmune thyroiditis, and Graves' disease. It has, in general, been difficult to separate antimicrosomal activity from that directed against the thyrotropin (TSH) receptor in Graves' IgG preparations. The "microsomal" antigen has been localized to the endoplasmic reticulum and microfollicular aspect of thyrocytes; its structure is however unknown. In an attempt to identify the thyroid microsomal antigen, we studied the interaction of Hashimoto's IgG with high microsomal antibody titre and negative for thyroglobulin with purified thyroid plasma and light microsomal membranes. We allowed Hashimoto's, Graves', and control IgGs to bind to protein blots of thyroid plasma membranes resolved on SDS-PAGE under non-reducing conditions. All seven Hashimoto's IgG at a concentration of 2 mg/ml interacted with an M approximately 197,000 polypeptide corresponding to the TSH holoreceptor. By contrast to Graves' IgG (which were positive at 1 mg/ml), however, this binding was not blocked by pretreatment of the protein blots with TSH. Normal IgGs showed no binding at concentrations of up to 2 mg/ml. Both Hashimoto's and Graves' IgG interacted with TSH-affinity column-purified receptor preparations. Two of the Hashimoto's IgGs induced adenylate cyclase activation in thyroid plasma membranes, three inhibited TSH-stimulated enzyme activation, and two were without effect. Two classes of autoantibodies, other than TSH receptor directed, were encountered; one class raised to antigens common to all seven patients and another class unique to individual patients, eg, Mr 210,000 and Mr 20,000 polypeptides. We propose that the TSH receptor has multiple epitopes (functional domains), and the one to which antimicrosomal antibody bind is likely to be spatially separated from that with which Graves' IgG and TSH interact. Differences in affinity or number of sites allows for the demonstration of Graves' IgG against a background of antimicrosomal antibody.  相似文献   

4.
Abstract. The aim of this study was to determine possible differences in peripheral blood mononuclear cells (PBMC) proliferation of healthy donors and Hashimoto's thyroiditis patients and whether a statistical approach to cell proliferation analysis might be used to discern the differences. The effect of a wide range of 2'-deoxyguanosine (dGuo) concentrations (0–1250 μM) on the mitogen-induced proliferation of PBMC was studied in healthy donors and Hasimoto's thyroiditis patients. Activity levels of purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) in PBMC were also measured. For the first time in a study of these models of dGuo toxicity in vitro , the analysis of polynomial trends of orders from 1 to 7 was applied to evaluate cell proliferation. A dose-dependent inhibition of mitogen-induced PBMC proliferation was observed in both groups. Data for linear trend established that PBMC from Hashimoto's thyroiditis patients were more sensitive to dGuo toxicity than PBMC from healthy donors. A positive quadratic trend at low dGuo doses was found in the cell proliferation of Hashimoto's thyroiditis patients. A decrease in PNP activity ( P < 0.025) and an increase in ADA activity ( P < 0.005) was observed in PBMC of Hashimoto's thyroiditis group. The differences in PBMC proliferation subjected to dGuo toxicity between the two groups could be related with the distinct pattern of purine salvage enzymes observed.  相似文献   

5.
Graves disease and Hashimoto's thyroiditis are autoimmune thyroid diseases (AITD) in which the genetic contribution is complex. The purpose of this work was to analyze the influence of hsp70 gene polymorphisms on the susceptibility to AITD. The hsp 70-2 and hsp 70-hom polymorphism was analyzed, by PCR-RFLP using PstI and NcoI enzymes, respectively, in 40 patients affected with AITD and 38 related healthy individuals belonging to a large consanguineous family named Akr. The transmission disequilibrium test (TDT) was applied on nuclear families, deduced from the Akr pedigree, with at least one heterozygous parent for each studied polymorphism. The corresponding x2 values for hsp 70-2 and hsp 70-hom were, respectively, of 0.52, p > 0.05 and 2.77, p > 0.05. Our data indicated lack of association between these hsp polymorphisms and AITD in this large family.  相似文献   

6.
Chemokines are a family of small, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with their seven-transmembrane, G protein-coupled receptors. Their major function is the recruitment of leukocytes to inflammation sites, but they also play roles in tumor growth, angiogenesis, organ sclerosis, and autoimmunity. A variety of evidence has accumulated to support the concept that thyroid follicular cells as well as intrathyroidal lymphocytes are able to produce CC and CXC chemokines, which, in turn, promote the initiation and maintenance of an inflammatory process resulting in autoimmune thyroid diseases (AITD). Overexpression of several chemokines in AITD has been demonstrated. Moreover, alterations of CCL2, CCL5, CXCL9, and CXCL10 have been shown in circulation of many patients with AITD. In subjects with Graves' disease, antithyroid drug treatment, radioactive iodine ablation, and thyroidectomy can significantly reduce CXCL10 levels. The measurement of chemokines in serum of AITD patients might provide a useful parameter for the evaluation and prediction of disease activity and progression. Further experimental and clinical studies will expand our understanding of the clinical implications of chemokine detection and the effects of chemokines on the pathogenesis of AITD.  相似文献   

7.
BACKGROUND: The etiology of the autoimmune thyroid diseases (AITDs), Graves' disease (GD) and Hashimoto's thyroiditis (HT), is largely unknown. However, genetic susceptibility is believed to play a major role. Two whole genome scans from Japan and from the US identified a locus on chromosome 8q24 that showed evidence for linkage with AITD and HT. Recent studies have demonstrated an association between thyroglobulin (Tg) polymorphisms and AITD in Caucasians, suggesting that Tg is a susceptibility gene on 8q24. OBJECTIVES: The objective of the study was to refine Tg association with AITD, by analyzing a panel of 25 SNPs across an extended 260 kb region of the Tg. METHODS: We studied 458 Japanese AITD patients (287 GD and 171 HT patients) and 221 matched Japanese control subjects in association studies. Case-control association studies were performed using 25 Tg single nucleotide polymorphisms (SNPs) chosen from a database of the Single Nucleotide Polymorphism Database (dbSNP). Haplotype analysis was undertaken using the computer program SNPAlyze version 7.0. PRINCIPAL FINDINGS AND CONCLUSIONS: In total, 5 SNPs revealed association with GD (P<0.05), with the strongest SNP associations at rs2256366 (P?=?0.002) and rs2687836 (P?=?0.0077), both located in intron 41 of the Tg gene. Because of the strong LD between these two strongest associated variants, we performed the haplotype analysis, and identified a major protective haplotype for GD (P?=?0.001). These results suggested that the Tg gene is involved in susceptibility for GD and AITD in the Japanese.  相似文献   

8.
Circulating chemokines in patients with autoimmune thyroid diseases.   总被引:2,自引:0,他引:2  
Chemokines are a group of small proteins that recruit different leukocyte subtypes to sites of inflammation and play important roles in initiating and maintaining immunological responses in autoimmune endocrine diseases including Graves' disease (GD) and Hashimoto's thyroiditis (HT). Previous studies have found increased gene and protein expression of different kinds of chemokines not only within the thyroid gland but also within thyroid cells in GD or HT patients. A few studies have determined serum levels of chemokines, with conflicting results. We measured circulating concentrations of CCL2, CCL5, CXCL9, and CXCL10 in patients with GD, HT, and nontoxic nodular thyroid disease (NNT). While CCL2 and CXCL9 concentrations were comparable in patients with either AITD or NNT, CCL5 was significantly increased in GD patients compared with HT or NNT subjects. In contrast, CXCL10 levels were lower in patients with GD, but the difference was statistically significant only when compared with patients with HT (p=0.0018). Importantly, GD patients who relapsed or went into remission had significantly different levels of CXCL9 (p=0.0252). Serum levels of CCL2, CCL5, CXCL9, and CXCL10 did not reveal any correlation with thyroid volume; with the levels of thyrotropin (TSH), FT3, or FT4; or with the titers of TSH receptor antibody and thyroperoxidase antibody. These data suggest that the expression patterns of chemokines in various thyroid diseases differ from each other, which may reflect the distinct immune responses in HT and GD.  相似文献   

9.
Human anti-thyroid peroxidase (TPO) autoantibodies (aAb) are generated during autoimmune thyroid diseases (AITD). Within recent years, increasing knowledge of the TPO-specific aAb repertoire, gained mainly by the use of combinatorial library methodology, has led to the cloning and sequencing of around 180 human anti-TPO aAb. Analysis of the immunoglobulin (Ig) variable (V) genes encoding the TPO aAb in the ImMunoGeneTics database (IMGT) (http://imgt.cines.fr) reveals major features of the TPO-directed aAb repertoire during AITD. Heavy chain VH domains of TPO-specific aAb from Graves' disease patients preferentially use D proximal IGHV1 genes, whereas those from Hashimoto's thyroiditis are characterized more frequently by IGHV3 genes, mainly located in the middle of the IGH locus. A large proportion of the anti-TPO heavy chain VH domains is obtained following a VDJ recombination process that uses inverted D genes. J distal IGKV1 and IGLV1 genes are predominantly used in TPO aAb. In contrast to the numerous somatic hypermutations in the TPO-specific heavy chains, there is only limited amino acid replacement in most of the TPO-specific light chains, particularly in those encoded by J proximal IGLV or IGKV genes, suggesting that a defect in receptor editing can occur during aAb generation in AITD. Among the predominant IGHV1 or IGKV1 TPO aAb, conserved somatic mutations are the hallmark of the TPO aAb repertoire. The aim of this review is to provide new insights into aAb generation against TPO, a major autoantigen involved in AITD.  相似文献   

10.
INTRODUCTION: Apoptosis, programmed cell death is a regulating mechanism enabling the removal of superabundantly produced and unnecessary at the certain moment cells. Disturbances of the apoptosis regulation contribute to the pathogenesis of many diseases, including autoimmune thyroid disorders. The aim of this study was to estimate expression of proapoptotic Fas/FasL and caspase-8 in thyroid tissues in patients with Graves' disease (GD), non-toxic nodular goiter (NTNG) and Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: Inclusion criteria of Graves' patients were: large goiter, ophthalmopathy, TRAb > 5 U/L, positive titre of anti-TPO and anti-TG antibodies and concentration of TSH < 0.45 microIU/mL for more the 2-3 months from an onset of the disease. Isolated thyrocytes were identified by indirect method: in the first stage mouse monoclonal antibodies (mAbs) anti-TPO were bound to rabbit anti-mouse antibodies IgG (Fab')2 labeled FITC. To obtained cellular suspension mAbs directed against apoptotic Fas/FasL molecules labeled with PE (Phycoerythrin) was added. All investigations were performed on Coulter EPICS XL flow cytometer. Detection of apoptotic proteins was confirmed by Western Blot and immunohistochemistry methods using mAbs in DAB chromogene visuality and marked by Mayer's haematoxylin. Evaluation of caspase-8 expression in thyroid follicular cells was performed by Western Blot test. RESULTS: The analysis of Fas and FasL expression on surface of thyroid follicular cells was higher in patients with Hashimoto's thyroiditis (38%, 26%) in comparison with patients with Graves' disease (18%, 14%). In case of patients with Hashimoto's thyroiditis significantly lower percentage of thyroid tissue infiltrating immune Fas+ (13%) and FasL+ (22%) T cells in comparison with Graves' patients (33%, 43% respectively) was observed . Identification of proapoptotic Fas and FasL molecules in the thyroid follicular cells revealed higher expression of both proteins in patients with GD (++,++) and HT (+++; +++, respectively) in comparison with NTNG patients (+/0; +/0). Caspase-8 expression was detected in band 55 kDa using Western Blot test in patients with thyroid autoimmune diseases. CONCLUSIONS: We conclude that alteration in the expression of proapoptotic proteins in thyroid follicular cells may play a role in pathogenesis of thyroid autoimmune disorders. In addition, suppression of apoptosis in Graves' disease led to increased proliferation of thyroid follicular cells which is responsible for goiter formation.  相似文献   

11.
Uveal autoantigen with coiled coil domains and ankyrin repeats (UACA) is an autoantigen in patients with panuveitis such as Vogt-Koyanagi-Harada disease. The prevalence of IgG anti-UACA antibodies in patients with uveitis is significantly higher than healthy controls, suggesting its potential role as an autoantigen. Originally, UACA was cloned from dog thyroid tissue following TSH stimulation. So, we presumed UACA could be a novel autoantigen in autoimmune thyroid diseases. We measured serum anti-UACA antibody titer using ELISA in patients with autoimmune thyroid diseases (Graves' disease, Hashimoto's thyroiditis, subacute thyroiditis, and silent thyroiditis). The prevalence of anti-UACA antibodies in Graves' disease group was significantly higher than that in healthy group (15% vs. 0%). Moreover, the prevalence of anti-UACA antibodies in Graves' ophthalmopathy was significantly higher than that in Graves' patients without ophthalmopathy (29% vs. 11%). Especially, 75% of severe ocular myopathy cases showed high UACA titer. Immunohistochemical analysis revealed that UACA protein is expressed in eye muscles as well as human thyroid follicular cells. Taken together, UACA is a novel candidate for eye muscle autoantigens in thyroid-associated ophthalmopathy.  相似文献   

12.
A subpopulation of lymphocytes forming rosettes with autologous erythrocytes was studied on peripheral blood and thyroid tissues obtained from the patients with various thyroid diseases. The mean (+/-S.D.) percentage of autorosette-forming cells (ARFC) was 10.1(+/-5.5)% in the peripheral blood from patients with hyperthyroid Graves' disease, which was higher than that in normal subjects (5.6 +/- 2.8%), while the levels of ARFC in the peripheral blood from euthyroid patients with Graves' disease under treatment and Hashimoto's thyroiditis did not significantly differ from the normal level. The mean percentages of ARFC in the thyroid tissues from patients with Graves' disease and Hashimoto's thyroiditis were 14.7(+/-8.5) and 13.3(+/-7.8)%, respectively, which were higher than those in the peripheral blood from the same patients. Most of these cases with abnormally high levels of ARFC were accompanied with the abnormally low T cell to B cell ratios. The microscopic examination of the cytological materials from these patients showed an increased number of large stimulated lymphoid cells or lymphoblasts as compared with those who had few ARFC. These results suggest an increase in an activated T cell subset in the circulation and/or in the thyroid tissue, which is probably caused by active immune response to some stimuli.  相似文献   

13.
The study aimed at determining the incidence of autoantibodies occurrence in the course of autoimmunological diseases of the thyroid gland and in healthy population. Autoantibodies against various structures were assayed, including: cellular nuclei, smooth muscles, mitochondria, biliary tubules, parietal cells, reticular fibres, striated muscles as well as thyroglobulin and thyroid microsomes. The study involved 63 patients with autoimmunological diseases of the thyroid gland (35 patients with Graves-Basedow disease and 28 patients with Hashimoto's disease) and 30 healthy individuals. Thyroid antimicrosomal and antithyroglobulin antibodies were assayed with RIA in stable phase whereas the remaining antibodies--with multifunctional indirect immunofluorescence test. The obtained results are the following: antimicrosomal antibodies were present in 68.3% cases while antithyroglobulin antibodies in 76.2% of the examined patients with autoimmunological diseases of the thyroid gland. Immunofluorescence tests performed in the same group have shown antinuclear antibodies in 13% of cases, antibodies against smooth muscles in 28.6%, antimitochondrial antibodies in 1.6%, antibodies against biliary tubules in 3.4%, antibodies against parietal cells in 11.1%, antibodies against reticular fibres in 7.9%, and antibodies against striated muscles in 9.5% of cases. Antinuclear antibodies, antibodies against smooth muscles, and antibodies against both thyroidal microsome and thyroglobulin (in 3.3%) were the only antibodies found in the control group.  相似文献   

14.
The expression and synthesis of insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) are regulated by various hormones and nutritional conditions. We evaluated the effects of thyroid hormones on serum levels of IGF-I and IGFBP-3 levels in patients with autoimmune thyroid diseases including 54 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis, and in 32 healthy age-matched control subjects. Patients were subdivided into hyperthyroid, euthyroid and hypothyroid groups that were untreated, or were treated with methylmercaptoimidazole (MMI) or L-thyroxine (L-T4). Serum levels of growth hormone (GH), IGF-I and IGFBP-3 were determined by radioimmunoassay. Serum GH levels did not differ significantly between the hyperthyroid and the age-matched euthyroid patients with Graves' disease. The serum levels of IGF-I and IGFBP-3 showed a significant positive correlation in the patients (R=0.616, P<0.001). The levels of both IGF-I and IFGBP-3 were significantly higher in the hyperthyroid patients with Graves' disease or in those with Hashimoto's thyroiditis induced by excess L-T4 administration than in control subjects. Patients with hypothyroid Graves' disease induced by the excess administration of MMI showed significantly lower IGFBP-3 levels as compared to those in healthy controls (P<0.05). Levels of IGFBP-3, but not IGF-I levels, showed a significant positive correlation with the levels of free T4 and free T3. In Graves' disease, levels of TPOAb, but not of TRAb, showed a significant positive correlation with IGFBP-3. We conclude that in patients with autoimmune thyroid diseases, thyroid hormone modulates the synthesis and/or the secretion of IGF-I and IGFBP-3, and this function is not mediated by GH.  相似文献   

15.
Plasmodium and other apicomplexan parasites are deficient in purine biosynthesis, relying instead on the salvage of purines from their host environment. Therefore, interference with the purine salvage pathway is an attractive therapeutic target. The plasmodial enzyme adenosine deaminase (ADA) plays a central role in purine salvage and, unlike mammalian ADA homologs, has a further secondary role in methylthiopurine recycling. For this reason, plasmodial ADA accepts a wider range of substrates, as it is responsible for deamination of both adenosine and 5′-methylthioadenosine. The latter substrate is not accepted by mammalian ADA homologs. The structural basis for this natural difference in specificity between plasmodial and mammalian ADA has not been well understood. We now report crystal structures of Plasmodium vivax ADA in complex with adenosine, guanosine, and the picomolar inhibitor 2′-deoxycoformycin. These structures highlight a drastic conformational change in plasmodial ADA upon substrate binding that has not been observed for mammalian ADA enzymes. Further, these complexes illuminate the structural basis for the differential substrate specificity and potential drug selectivity between mammalian and parasite enzymes.  相似文献   

16.
Two common forms of autoimmune thyroid diseases are Graves' disease and Hashimoto's thyroiditis. Cytotoxic T lymphocyte antigen 4 (CTLA4) encoded by the CTLA4 gene on chromosome 2q33 plays a role in susceptibility to Graves' disease and is probably important also for Hashimoto's thyroiditis as well as for the other endocrine autoimmune disorders. The CTLA4 locus is the only nonhuman leukocyte antigen locus that has been found in association with Graves' disease repeatedly. Particularly, association of three polymorphic markers of CTLA4 gene, namely, C(-318)T, A49G, and (AT)n dinucleotide repeat, with Graves' disease was demonstrated in most of the population-based investigations. On the other hand, there are few studies to reveal the association of these markers with Hashimoto's thyroiditis. A49G polymorphism was proposed to be associated with Hashimoto's thyroiditis, and C(-318)T was suggested to be not associated. The patient groups consisted of 88 patients (10 males and 78 females; mean age: 14.5 +/- 3.2 years [4.6-21.0 years]) with a previous diagnosis of Hashimoto's thyroiditis and 112 euthyroid volunteers (51 males and 61 females; mean age: 14.1 +/- 2.9 years [5.2-18 years]). The frequency of A/G (A49G) genotype was high and statistically significant in patients with Hashimoto's thyroiditis in comparison with the control group. Although the frequency of C/T [C(-318)T] genotype is not significantly high in children with Hashimoto's thyroiditis according to the control group, the risk of Hashimoto's thyroiditis in A/G genotype group was 4.66 times greater than the group with A/A genotype. In this study, we documented that the A49G polymorphism might increase the susceptibility for Hashimoto's thyroiditis.  相似文献   

17.
OBJECTIVES: Thymidine kinase (TK, EC 2.7.1.21) is a part of the pyrimidine salvage pathway, involved in DNA synthesis. In turn, adenosine kinase (AK, EC 2.7.1.20) functions as a part of the purine metabolic pathway, involved in DNA synthesis. Melatonin (Mel) is an indoleamine which is known to inhibit growth processes in the thyroid gland and also in other endocrine and non-endocrine tissues. The aim of our study was to examine TK and AK activities in homogenates of the rat thyroid lobes remaining after contralateral hemithyroidectomy (hemiTx); additionally, incubations with Mel (10(-6), 10(-9), and 10(-12) M) were performed. METHODS: The experiment was performed on young male Wistar rats (6-week old). The enzyme activities were measured by ascending chromatography and expressed as the amounts of radioactive reaction products of the phosphorylation of dThd (for TK) and of dAdo (for AK). RESULTS: 1. HemiTx increased TK activity in homogenates of the remaining thyroid lobe; 2. Mel increased TK activity in all the groups (intact, sham-operated- and hemiTx-rats), except for the concentrations of 10(-9) and 10(-12) M in the hemiTx-rats, in which the increasing effects of Mel on TK activity reached the borderline statistical significance only; 3. Mel increased the AK activity in intact and in shamTx animals; 4. No statistically significant changes were found in AK activity following Mel in vitro in the incubated remaining thyroid lobes, collected from hemiTx-rats.  相似文献   

18.
An immunofluorescence study using unfixed cryostat sections of rat pituitary glands was carried out on sera from 34 patients with Hashimoto's thyroiditis, 28 patients with Graves' disease, 10 patients with thyroid adenoma and 50 healthy subjects. After absorption of sera with rat liver tissues, 19 of 34 patients retained reactivity to anterior pituitary cell antibodies (PCA, 55.8%). On the other hand, immunofluorescence in anterior pituitary cells was faint and detected in only 2 of 28 patients with Graves' disease (7.1%) after absorption of their sera with rat liver aceton powder. A similar result was also obtained when PCA were compared in the sera of Hashimoto's thyroiditis and Graves' disease with high titers of thyroid microsomal autoantibodies. PCA were detected neither in the sera of patients with thyroid adenoma nor in the healthy subjects. The present study suggests that PCA were considerably more prevalent in Hashimoto's thyroiditis than in Graves' disease.  相似文献   

19.
Genetic studies have identified the HLA and CTLA4 regions as susceptibility loci for the development of common autoimmune thyroid diseases (AITDs), including Graves' disease and autoimmune hypothyroidism. Despite numerous studies, the identification of a third locus has remained elusive. Genetic-linkage studies have implicated chromosome 8q24 as a susceptibility locus for AITD. The gene encoding thyroglobulin (Tg), which encodes a major thyroid autoantigen, maps to this region, and a recent study has reported the association of several exonic single-nucleotide polymorphisms (SNPs) with disease. Although these preliminary data are potentially exciting, caution needs to be exercised, and replication of the data sought before Tg can be designated as the third locus for AITD.  相似文献   

20.
Studies on purine enzymes in experimental colitis   总被引:4,自引:0,他引:4  
Although the role of adenosine deaminase (ADA), adenylate deaminase (AMP-DA), purine nucleoside phosphorylase (PNP) is well documented in gastric and intestinal carcinoma, their role in inflammatory bowel diseases remains unknown. In the present study, we investigated the profile of these enzymes in blood and intestinal tissues during colitis. Colitis induced in Wistar rats by acetic acid was monitored by a marker enzyme myeloperoxidase (MPO). The tissue levels of MPO increased on 1, 2, 5 and 6 days post-administration (PA) of acetic acid and declined to the control levels by day 7 PA. In parallel the blood levels of ADA and AMP-DA decreased on days 1, 2 and 5 without any significant change on days 6 and 7 PA. Similar observations were recorded for these enzymes in the cytosolic extracts of colonic tissue specimens. In contrast, PNP remained unaltered in both blood and tissue samples. These findings suggest an inverse-relationship between inflammation and purine deaminases in both blood and tissues.  相似文献   

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