scholarly journals CTLA-4 gene polymorphisms and their influence on predisposition to autoimmune thyroid diseases (Graves’ disease and Hashimoto’s thyroiditis)

2012 ◽  
Vol 3 ◽  
pp. 415-421 ◽  
Author(s):  
Dorota Pastuszak-Lewandoska ◽  
Ewa Sewerynek ◽  
Daria Domańska ◽  
Aleksandra Gładyś ◽  
Renata Skrzypczak ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Gene Polymorphisms ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

scholarly journals Defect of a subpopulation of natural killer immune cells in Graves’ disease and Hashimoto’s thyroiditis: normalizing effect of dehydroepiandrosterone sulfate

2005 ◽  
Vol 152 (5) ◽  
pp. 703-712 ◽  
Author(s):  
Sebastiano Bruno Solerte ◽  
Sara Precerutti ◽  
Carmine Gazzaruso ◽  
Eleonora Locatelli ◽  
Mauro Zamboni ◽  
...  
Keyword(s):  
Nk Cells ◽  
Hashimoto’S Thyroiditis ◽  
Nk Cell ◽  
Secretory Activity ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Tnf Α

Background: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves’ disease (GD) and Hashimoto’s thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. Objective: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. Design: We studied 13 patients with recent onset Graves’ disease, 11 patients with Hashimoto’s thyroiditis at first diagnosis and 15 age-matched healthy subjects. Methods: NK cells were concentrated at a density of 7.75 × 106 cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16 + /CD56 + cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-β (IFN-β) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-α (TNF-α) from NK cells. Results: Lower spontaneous, IL-2- and IFN-β-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P < 0.001). A decrease in spontaneous and IL-2-modulated TNF-α release from NK cells was also found in both groups of patients (P < 0.001). The co-incubation of NK cells with IL-2/IFN-β + DHEAS at different molar concentrations (from 10−8 to 10−5 M/ml/NK cells) promptly normalized NKCC and TNF-α secretion in GD and HT patients. Conclusions: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.

scholarly journals Polymorphisms of IKZF3 Gene and Autoimmune Thyroid Diseases: Associated with Graves’ Disease but Not with Hashimoto’s Thyroiditis

2018 ◽  
Vol 45 (5) ◽  
pp. 1787-1796 ◽  
Author(s):  
Ling Li ◽  
Xiaolian Ding ◽  
Xuan Wang ◽  
Qiuming Yao ◽  
Xiaoqing Shao ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Zinc Finger Protein ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Control Group ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Significant Difference ◽  
Proliferation And Differentiation

Background/Aims: The IKZF3 gene encodes a zinc-finger protein that plays an important role in the proliferation and differentiation of B lymphocytes. Autoimmune thyroid diseases (AITDs), mainly include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are probably caused by the aberrant proliferation of B cells. The objective of this study was to explore the association between IKZF3 polymorphisms and AITDs. Methods: We examined 915 AITD patients (604 GD and 311 HT) and 814 healthy controls. IKZF3 variants (rs2941522, rs907091, rs1453559, rs12150079 and rs2872507) were tested by PCR-ligase detection reaction. Results: It was manifested that that the minor alleles of the five loci increased susceptibility to GD (p<0.05 for rs2941522, and p<0.01 for rs907091, rs1453559, rs12150079 and rs2872507) but in HT patients, these loci showed no significant difference compared with controls. Similarly, the genotype distributions of GD patients manifested obvious differences in all these loci compared with the control group, whereas no statistical differences were observed between HT patients and controls. Furthermore, bioinformatics tools were used to analyze rs1453559, rs12150079 and rs907091. These variants were believed to be the transcription regulator. Conclusion: It is the first time we reported the association between the IKZF3 polymorphisms and GD, indicating that IKZF3 gene tends to bean important risk factor for the development of GD.

scholarly journals IRF7 Gene Variations Confer Susceptibility to Autoimmune Thyroid Diseases and Graves’ Ophthalmopathy

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Qiuming Yao ◽  
Xiaofei An ◽  
Jing Zhang ◽  
Kaida Mu ◽  
Ling Li ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Susceptibility Gene ◽  
Thyroid Diseases ◽  
Minor Allele ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Graves Ophthalmopathy ◽  
Significant Difference

The objective of this study was to investigate whether IRF7 polymorphisms are associated with autoimmune thyroid diseases (AITDs). We selected three single nucleotide polymorphisms (SNPs) of IRF7, namely, rs1061501, rs1131665, and rs1061502 for genotyping using PCR-based ligase detection reaction (LDR) method in a total of 1659 participants (592 with Graves’ disease, 297 with Hashimoto’s thyroiditis, and 770 healthy controls). Gene-disease and genotype-clinical phenotype associations were evaluated for the three SNPs. Our results showed that the AG genotype and the minor allele G frequency of rs1131665 and rs1061502 in AITD patients were both higher than those of the controls (rs1131665: AG genotype: P=0.017, OR=1.968; allele G: P=0.018, OR=1.946; rs1061502: AG genotype: P=0.029, OR=1.866; allele G: P=0.031, OR=1.847). Subgroup analysis also showed that the AG genotype and the minor allele G frequency of rs1131665 and rs1061502 in Graves’ disease patients were both higher than those of the controls (rs1131665: AG genotype: P=0.015, OR=2.074; allele G: P=0.016, OR=2.048; rs1061502: AG genotype: P=0.034, OR=1.919; allele G: P=0.035, OR=1.898). Furthermore, the allele G frequency of rs1061501 was associated with Graves’ ophthalmopathy (P=0.035, OR=1.396). No significant difference in IRF7 polymorphisms was found between Hashimoto’s thyroiditis patients and controls. Our study has revealed for the first time that IRF7 is a susceptibility gene for AITD, especially for Graves’ disease and Graves’ ophthalmopathy.

scholarly journals Risk Factors Associated with Benign and Malignant Thyroid Nodules in Autoimmune Thyroid Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Priscila Carneiro Moreira Lima ◽  
Arnaldo Moura Neto ◽  
Marcos Antonio Tambascia ◽  
Denise Engelbrecht Zantut Wittmann
Keyword(s):  
Thyroid Carcinoma ◽  
Hashimoto’S Thyroiditis ◽  
Thyroid Nodules ◽  
Thyroid Volume ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Demographical Data

Objectives. Assess the prevalence of thyroid nodules and predictors of malignant origin in patients with autoimmune thyroid diseases. Patients and Methods. Retrospective study including 275 patients, 198 with Graves' disease and 77 with Hashimoto’s thyroiditis. Clinical and demographical data, ultrasonographical nodule characteristics, total thyroid volume and histological characteristics were recorded. Results. Graves’ disease: the prevalence of thyroid nodules and thyroid carcinoma were 27.78% and 5.05%, respectively. Older age (OR = 1.054; 95% CI = 1.029–1.080) and larger thyroid volumes (OR = 1.013; 95% CI = 1.003–1.022) increased the chance of nodules. Younger age (OR = 1.073; 95% CI = 1.020–1.128) and larger thyroid volume (OR = 1.018; 95% CI = 1.005–1.030) predicted thyroid carcinoma. Hashimoto’s thyroiditis: the prevalence of thyroid nodules and carcinomas were 50.7% and 7.8%, respectively. Nodules were predicted by thyroid volume (OR = 1.030; 95% CI = 1.001–1.062). We found higher number of nodules in patients with thyroid carcinoma than in those with benign nodules (3 versus 2; ). Patients with Hashimoto’s thyroiditis presented nodules more frequently than patients with Graves’ disease (50.65% versus 27.28%; ), while the prevalence of carcinoma was similar (). Conclusions. Larger goiter was associated with carcinoma in Graves’ disease and Hashimoto’s thyroiditis. Younger patients presented higher risk of papillary thyroid carcinoma in Graves’ disease. The prevalence of carcinoma was similar in both conditions.

scholarly journals Polymorphisms in Autophagy-Related Gene IRGM Are Associated with Susceptibility to Autoimmune Thyroid Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Qiu-ming Yao ◽  
Yuan-feng Zhu ◽  
Wen Wang ◽  
Zhen-yu Song ◽  
Xiao-qing Shao ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Susceptibility Gene ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Related Gene ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Significant Difference ◽  
Disease Associations

Background. To date, studies have shown that polymorphisms in an autophagy-related gene, IRGM, are linked with different diseases, especially autoimmune diseases. The present study aimed to examine the roles of IRGM polymorphisms in autoimmune thyroid diseases (AITD). Methods. Three polymorphisms in IRGM gene (rs10065172, rs4958847, and rs13361189) were genotyped in 1569 participants (488 with Graves’ disease, 292 with Hashimoto’s thyroiditis, and 789 healthy controls) using PCR-based ligase detection reaction method. Gene-disease associations were evaluated for the three SNPs. Results. T allele of rs10065172, A allele of rs4958847, and C allele of rs13361189 were all higher in Graves’ disease patients than controls, and the ORs were OR = 1.207 (P=0.022), OR = 1.207 (P=0.027), and OR = 1.200 (P=0.027), respectively. After adjusting for sex and age, rs10065172 and rs13361189 were still associated with GD under both the allele model and dominant model, and the adjusted ORs for rs10065172 were 1.20 (P=0.033) and 1.33 (P=0.024), while the adjusted ORs for rs13361189 were 1.19 (P=0.042) and 1.33 (P=0.026), respectively. No significant difference was found between Hashimoto’s thyroiditis patients and controls. Haplotype analysis found that CTA frequency was distinguishingly higher in Graves’ disease patients (OR = 1.195, P=0.030). The frequency of TCG haplotype was distinguishingly lower in AITD and Graves’ disease patients (OR = 0.861, P=0.044; OR = 0.816, P=0.017). Conclusions. Our study reveals IRGM as a susceptibility gene of AITD and Graves’ disease for the first time.

scholarly journals Pendrin Is a Novel Autoantigen Recognized by Patients with Autoimmune Thyroid Diseases

2009 ◽  
Vol 94 (2) ◽  
pp. 442-448 ◽  
Author(s):  
Akio Yoshida ◽  
Ichiro Hisatome ◽  
Shinichi Taniguchi ◽  
Yasuaki Shirayoshi ◽  
Yasutaka Yamamoto ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Sodium Iodide ◽  
Chloride Transport ◽  
Thyroid Diseases ◽  
Tsh Receptor ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Sodium Iodide Symporter ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

Abstract Context: Pendrin is an apical protein of thyroid follicular cells, responsible for the efflux of iodide into the follicular lumen via an iodide-chloride transport mechanism. It is unknown whether pendrin is recognized by autoantibodies. Objective: Our objective was to examine the prevalence of pendrin antibodies in autoimmune thyroid diseases and compare with that of thyroglobulin, thyroperoxidase, TSH receptor, and sodium iodide symporter antibodies. Design: In a prevalent case-control study, we analyzed the sera of 140 autoimmune thyroid disease cases (100 with Graves’ disease and 40 with Hashimoto’s thyroiditis) and 80 controls (50 healthy subjects, 10 patients with papillary thyroid cancer, 10 with systemic lupus erythematosus, and 10 with rheumatoid arthritis). Pendrin antibodies were measured by immunoblotting using extract of COS-7 cells transfected with pendrin and a rabbit polyclonal pendrin antibody. Results: Pendrin antibodies were found in 81% of the cases and 9% of controls (odds ratio = 44; P &lt; 0.0001). Among cases, pendrin antibodies were more frequent and of higher titers in Hashimoto’s thyroiditis than in Graves’ disease. Pendrin antibodies correlated significantly with thyroglobulin, thyroperoxidase, and sodium iodide symporter antibodies but not with TSH receptor antibodies. Pendrin antibodies were equally effective as thyroglobulin and thyroperoxidase antibodies in diagnosis of autoimmune thyroid diseases, especially Hashimoto’s thyroiditis. Conclusions: The study identifies pendrin as a novel autoantigen recognized by patients with autoimmune thyroid diseases and proposes the use of pendrin antibodies as an accurate diagnostic tool.

Assessment of thyroid growth stimulating activity of immunoglobulins from patients with autoimmune thyroid diseases by cytokinesis arrest assay

1997 ◽  
Vol 136 (5) ◽  
pp. 499-507 ◽  
Author(s):  
Shinichi Miyamoto ◽  
Kanji Kasagi ◽  
Mohammad Sayeedul Alam ◽  
Takashi Misaki ◽  
Yasuhiro Iida ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Normal Subjects ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Thyroid Cell ◽  
Dependent Manner ◽  
Autoimmune Thyroid Diseases ◽  
Thyroid Cells ◽  
Autoimmune Thyroid

Abstract Objective: To develop a novel bioassay for the assessment of thyroid cell growth stimulating activity using cytochalasin B (CB) and to test immunoglobulins (IgGs) from patients with autoimmune thyroid diseases. Design: The assay is based on the principle that growing cells during incubation with CB show an increased number of nuclei in a cell (N/C index), since CB. at appropriate concentrations, is known to inhibit cytoplasmic cleavage without affecting nuclear mitosis. The N/C index represents potential DNA production while cells are incubated with CB. Methods: FRTL-5 thyroid cells were incubated with various thyroid stimulators in TSH-free medium containing 2 mg/l CB for 3 days. After the incubation, the cells were harvested in trypsin/EDTA to obtain single cell suspension, fixed, dropped onto a glass slide, stained and observed under a microscope to determine the N/C index. Results: Bovine TSH at 10−3–1·0 U/l, forskolin at 1×10−7–10−5 mol/l, cholera toxin at 10×10−5–10−3 mg/l, or (Bu)2cAMP at 1× 10−5–10−3 mol/l increased the N/C index up to approximately 2·0 in a dose-dependent manner. IgGs not only from 27 patients with untreated goitrous Graves' disease but also from 14 patients with goitrous Hashimoto's thyroiditis elicited an increase in the N/C index, which exceeded the mean+2s.d. of the values for 17 normal subjects (mean ± s.d., 1·063 ±0.014). Four patients with primary myxedema displayed a normal N/C index. In Graves' disease, the N/C index did not correlate significantly with thyroid stimulating antibodies (TSAb) activities but did correlate significantly with estimated goiter size (P<0·05). IgGs containing blocking-type TSH-receptor antibodies inhibited the TSH- or Graves' IgG-stimulated increase in N/C index almost completely, but did not influence the stimulatory effect of IgG from two patients with Hashimoto's thyroiditis. Conclusions: We have developed a sensitive and simple assay for thyroid growth stimulating activity by using CB, and found that all tested patients with goitrous Graves' disease and goitrous Hashimoto's thyroiditis have thyroid growth stimulating immunoglobulins whose activity does not correlate with TSAb. European Journal of Endocrinology 136 499–507

scholarly journals The role of apoptosis in development of autoimmune thyroid diseases

2009 ◽  
Vol 8 (1) ◽  
pp. 64-70
Author(s):  
Yu. V. Nedosekova ◽  
O. I. Urasova ◽  
Ye. B. Kravets ◽  
A. V. Chaikovsky
Keyword(s):  
Thyroid Gland ◽  
Hashimoto’S Thyroiditis ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Immunological Abnormalities ◽  
Apoptotic Factors

In the review representations about a role apoptosis by autoimmune thyroid diseases, such as Graves' disease and Hashimoto's thyroiditis, the basic pathogenetic links immunological abnormalities at the these diseases have been discussed. At has been demonstrated changes in a thyroid gland, and also changes endocellular pro- and anti-apoptotic factors are shown at Hashimoto's thyroiditis and Graves' disease.

scholarly journals Clinical Significance of Autoantibodies to Parietal Cells in Patients with Autoimmune Thyroid Diseases

Folia Medica ◽  
2013 ◽  
Vol 55 (2) ◽  
pp. 26-32 ◽  
Author(s):  
Julieta B. Gerenova ◽  
Irena M. Manolova ◽  
Vania I. Tzoneva
Keyword(s):  
Atrophic Gastritis ◽  
Clinical Significance ◽  
Thyroid Function ◽  
Hashimoto’S Thyroiditis ◽  
Thyroid Diseases ◽  
Parietal Cells ◽  
Hashimoto's Thyroiditis ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Function Group

ABSTRACT Clinical significance of autoantibodies to parietal cells (PCA) in patients with autoimmune thyroid diseases (ATD) remains contradictory. AIM: To characterize the frequency of PCA in patients with ATD; to clarify the role of gender and age in PCA positivity; to analyze the association of PCA with gastric or haematologic symptoms and with the levothyroxine dose required to achieve a serum TSH level within the normal range in treated Hashimoto’s thyroiditis (HT) patients. PATIENTS AND METHODS: PCA were measured using ELISA in 137 HT patients, divided into tree subgroups according to the thyroid function: group I included subjects with normal thyroid function; group II included patients with hypothyroidism, in group III were enrolled subjects treated with levothyroxine (LT4). We also studied the PCA positivity in 14 patients with active Graves’ disease and in 23 healthy controls. RESULTS: PCA positivity was found in 51 patients with autoimmune thyroid diseases, with an overall prevalence of 33.8%. No significant differences in PCA were observed between the groups of HT patients. The frequency of PCA in both genders was similar and there were no difference depending on age. In 7.3% of HT patients in different stages of disease we found clinically relevant gastric and/or haematologic symptoms; in 70% of them PCA were positive (OR = 5.5; 95% CI: 1.2 - 28.4; p = 0.009). PCA positive hypothyroid HT patients required higher LT4 doses than PCA negative (1.46 μg/kg vs 1.24 μg/kg, p = 0.04). CONCLUSIONS: PCA may be present in different stages in HT patients; this does not depend on the severity of disease. PCA concentrations may predict symptoms of atrophic gastritis in patients with Hashimoto’s thyroiditis. PCA positive HT patients require higher replacement doses of LT4. Presence of anemia, particularly microcytic anemia, was suggestive of undiagnosed atrophic gastritis.

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