scholarly journals Graves’ disease and Hashimoto’s thyroiditis in monozygotic twins: case study as well as transcriptomic and immunohistological analysis of thyroid tissues

2006 ◽  
Vol 154 (1) ◽  
pp. 13-20 ◽  
Author(s):  
G Aust ◽  
K Krohn ◽  
N G Morgenthaler ◽  
S Schröder ◽  
A Schütz ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hashimoto’S Thyroiditis ◽  
Thyroid Tissue ◽  
Monozygotic Twins ◽  
Hashimoto's Thyroiditis ◽  
Simultaneous Occurrence ◽  
Graves Disease ◽  
Autoimmune Thyroid ◽  
Extracellular Matrix Components ◽  
Lymphocytic Infiltrates

Objective: To report on the rare simultaneous occurrence of Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) in monozygotic twins. Design: We compared the pattern of thyroid tissue-derived cDNAs to gain insight into previous and ongoing immune destruction and reconstruction processes using microarrays. The results were confirmed by immunohistology and real-time PCR. Results: Destruction of thyroid tissue in HT reduced levels of thyrocyte-related cDNAs and cDNAs encoding extracellular matrix components, but increased levels of proteases involved in extracellular matrix degradation compared with GD. Lymphocytic infiltrates forming ectopic follicles replaced the thyroid tissue almost completely in HT. Thus, lymphocyte-related cDNA levels were higher in HT than in GD. The same was true for many chemokines and their receptors, which not only enable migration towards the thyroid but also maintain the lymphocytic infiltrate. HT also showed increased levels of cDNAs encoding molecules related to apoptosis than did GD. Surprisingly, the Th1- and Th2-specific cytokine profiles suggested for HT and GD respectively could not be confirmed. cDNAs encoding factors and receptors involved in angiogenesis were increased in GD compared with HT. Conclusions: Comparison of gene expression reflects the cellular differences between the two types of autoimmune thyroid disease in twins with identical genetic and similar environmental background.

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 Autoantibodies from patients with autoimmune thyroid disease do not interfere with the activity of the human iodide symporter gene stably transfected in CHO cells

2001 ◽  
pp. 611-618 ◽  
Author(s):  
M Tonacchera ◽  
P Agretti ◽  
G Ceccarini ◽  
R Lenza ◽  
S Refetoff ◽  
...  
Keyword(s):  
Cell Line ◽  
Cho Cells ◽  
Hashimoto’S Thyroiditis ◽  
Time Course ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Dependent Manner ◽  
Iodide Uptake ◽  
Autoimmune Thyroid ◽  
A Cell

OBJECTIVE: The human sodium iodide symporter (hNIS) is a candidate autoantigen in autoimmune thyroid diseases. To investigate the possible existence of autoantibodies able to interfere with the biological activity of hNIS, an assay was developed using a cell line stably expressing hNIS. METHODS: hNIS complementary cDNA cloned in pcDNA3 and a neomycin resistance gene vector were co-transfected into CHO cells. After selection with geneticin, a cell line termed PA4, showing the highest level of Na(125)I uptake, was characterized. The time course of iodide uptake was evaluated by incubating PA(4) cells with 10 micromol/l NaI and 0.1 microCi Na(125)I for a period up to 90 min. The accumulation of iodide increased linearly between 2 and 10 min, reaching a plateau at 45 min. The curve of iodide efflux mirrored that of iodide influx. Both perchlorate and thiocyanate inhibited iodide uptake in PA(4) cells in a dose-dependent manner starting from concentrations as low as 0.01 and 0.1 micromol/l respectively and complete inhibition was obtained at concentrations of 100 micromol/l perchlorate and 1000 micromol/l thiocyanate. The sensitivity of the inhibition assay was further improved using both inhibitors after 5 min incubation and in the absence of cold NaI. RESULTS: Included in the study were 42 patients with Graves' disease (25 had active hyperthyroidism, ten were euthyroid and seven had hypothyroidism); 34 patients with Hashimoto's thyroiditis (one was euthyroid, four had subclinical hypothyroidism and 29 were overtly hypothyroid); and 19 with atrophic thyroiditis (all hypothyroid). Four out of eight whole sera from patients with Hashimoto's thyroiditis, and 8 out of 25 whole sera from patients with Graves' disease caused an inhibition of iodide uptake in PA(4) cells greater than 20% but also in 4 out of 15 sera from normal subjects. This inhibition activity exerted by sera from patients and controls was lost after dialyzing against buffer. Accordingly, IgGs purified from sera of all patients with Graves' disease and with Hashimoto's thyroiditis or atrophic thyroiditis were devoid of any effect on iodide uptake. CONCLUSIONS: In conclusion, we believe that autoantibodies able to block the function of hNIS are very rare.

scholarly journals Thyrotropin-producing pituitary adenoma associated with Graves' disease

2004 ◽  
pp. 587-594 ◽  
Author(s):  
N Koriyama ◽  
M Nakazaki ◽  
H Hashiguchi ◽  
K Aso ◽  
Y Ikeda ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Hashimoto’S Thyroiditis ◽  
Somatostatin Receptor ◽  
Thyroid Tissue ◽  
Tumor Resection ◽  
Ppar Gamma ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

OBJECTIVES: The examination of potential associations between Graves' disease and thyrotropin-producing pituitary adenoma (TSHoma) after treatment using octreotide, and of the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma). DESIGN AND METHODS: A specimen of resected TSHoma tissue from our case was immunohistochemically examined for expression of somatostatin receptor 2A (SSTR2A) and PPAR gamma. Specimens of thyroid tissue from two cases with Hashimoto's thyroiditis were immunohistochemically examined for expression of SSTR2A. RESULTS: Expression of SSTR2A and PPAR gamma was identified in TSHoma cells. SSTR2A was also expressed in lymphocytes that had infiltrated thyroid tissue in Hashimoto's thyroiditis. In previous reports, three of four patients with TSHoma displayed Graves' disease after tumor resection, and TSH is also known to play a major role in regulating immunomodulatory gene expression in thyrocytes. CONCLUSIONS: Both the immunomodulatory effects of octreotide on intrathyroidal lymphocytes and rapid reductions in TSH may contribute to the onset of Graves' disease. Patients with TSHoma-associated autoimmune thyroiditis should undergo careful follow-up for development of Graves' disease after treatment. Both octreotide and the PPAR gamma receptor-activating ligands, thiazolidinediones, may be effective for patients with TSHoma.

Intrathyroidal cytokine gene expression profiles in autoimmune thyroiditis

1994 ◽  
Vol 141 (2) ◽  
pp. 309-315 ◽  
Author(s):  
R Paschke ◽  
F Schuppert ◽  
M Taton ◽  
T Velu
Keyword(s):  
Autoimmune Thyroiditis ◽  
Hashimoto’S Thyroiditis ◽  
Thyroid Tissue ◽  
Human Thyroid ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Thyroid Glands ◽  
Normal Human ◽  
Ifn Γ ◽  
Cytokine Mrnas

Abstract Cytokines are thought to mediate the initiation and perpetuation of autoimmune thyroiditis. However, this concept is mainly based on in vitro findings and to date only interleukin (IL)-6 and interferon-γ (IFN-γ) have been detected in Graves' disease in vivo. The cytokine pattern produced by T-helper (Th) cells has important regulatory effects on the nature of the immune response. We therefore determined these cytokine mRNAs in Graves' disease and Hashimoto's thyroiditis. RNA was extracted by cesium chloride gradient centrifugation from the thyroid tissue of 12 patients undergoing thyroid resection for Graves' disease and from two patients being treated for Hashimoto's thyroiditis. Two patients with parathyroid adenomas and one patient with a goiter were used as controls. RNA was also extracted from normal human thyroid epithelial cells in primary culture. The cDNAs were prepared by reverse transcription and amplified for IL-2, -4, -5, -6 and -10 and IFN-γ by polymerase chain reaction. All the cytokine mRNAs were detected in the Hashimoto's thyroid glands in large quantities. Six of the 12 Graves' disease thyroid glands showed, when compared with controls, an increased accumulation of transcripts for: IFN-γ, IL-2, -4 and -10 or IL-2, -4 and IFN-γ or IL-2 and IFN-γ or IFN-γ alone, each in one case or IL-2 alone in two cases. These cytokine profiles were not representative of a Th1 or Th2 phenotype. Increased amounts of cytokine mRNA in thyroid glands from Graves' disease patients were mostly associated with high microsomal antibody titres and/or prominent intrathyroidal lymphocytic infiltration. IL-6 and/or IL-10 mRNAs were detectable in all Graves' disease thyroid glands and in control thyroid tissue. IL-10 mRNA was not detectable in normal human thyroid epithelial cells in primary culture. Graves' disease and Hashimoto's thyroiditis clearly differ with respect to the number of positive intrathyroidal cytokine mRNAs and their levels. The different cytokine patterns in Graves' disease and in Hashimoto's thyroiditis could reflect the clinical spectrum of autoimmune thyroiditis which is characterized by thyroid tissue destruction and/or thyroid autoantibody production. These data suggest that the course of autoimmune thyroiditis is regulated by the interplay of several cytokines. Journal of Endocrinology (1994) 141, 309–315

GRAVES' DIEASE AND HASHIMOTO'S THYROIDITIS IN MONOZYGOUS TWINS

1973 ◽  
Vol 72 (1) ◽  
pp. 18-24 ◽  
Author(s):  
Bruce S. Chertow ◽  
William J. Fidler ◽  
Bruce L. Fariss
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Monozygotic Twins ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Thyroglobulin Antibodies ◽  
Protein Binding Assay ◽  
Competitive Protein Binding Assay ◽  
Competitive Protein Binding ◽  
High Concentrations ◽  
Monozygous Twins

ABSTRACT Monozygous twins and their family were studied. One twin had Graves' disease and the other had Hashimoto's thyroiditis. Their mother had Hashimoto's thyroiditis and their maternal grandmother and maternal great aunt had hyperthyroidism. Thyroid biopsies were obtained in each of the twins and showed changes of Graves' disease and Hashimoto's thyroiditis, respectively. High concentrations of anti-thyroid microsomal and anti-thyroglobulin antibodies were present by competitive protein binding assay, but LATS was absent in the twins and their mother. The occurrence of Graves' disease and Hashimoto's thyroiditis in monozygotic twins supports the concept of a common genetic aetiologic factor in the basic pathogenesis of these two diseases; however, the expression of this factor is variable, acquired, and, at least in part, genetically independent.

Determination of serum neopterin levels in patients with autoimmune thyroid diseases

2012 ◽  
Vol 153 (29) ◽  
pp. 1127-1131 ◽  
Author(s):  
Csaba Balázs ◽  
Boglárka Türke ◽  
Árpád Vámos
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Thyroid Stimulating Hormone ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Important Indicator ◽  
Autoimmune Thyroid ◽  
Serum Neopterin ◽  
Antibody Levels ◽  
Stimulating Hormone

An elevated serum level of neopterin indicates the activation of the cellular immune system. Aim: The objective was to find a correlation in autoimmune thyroid patients between neopterin levels and the clinical stage of the disease and to examine whether neopterin can predict the relapse of the disease. Methods: Serum neopterin, thyroid stimulating hormone, free thyroxine, free triiodothyronine, anti-thyroglobulin and anti-thyroid peroxidase antibody levels were determined in 137 patients with Graves’ disease (in different stages), 25 with Hashimoto’s thyroiditis and 14 with toxic adenoma. Results: The neopterin levels were significantly higher in patients with Graves’ disease (hyper-, eu-, hypothyroidism and relapsed hyperthyroidism) and Hashimoto’s thyroiditis. Positive correlation was found between neopterin and anti-thyroglobulin and anti-tyhroid peroxidase antibody levels, but no correlation was detected between neopterin levels and thyroid hormones, thyroid stimulating hormone values and antibodies against thyroid stimulating hormone receptors. Conclusions: Higher level of serum neopterin reflects an underlying autoimmune process, and does not correlate with changes in thyroid hormone levels. Determination of neopterin level can be an important indicator in the exacerbation of autoimmune processes. Orv. Hetil., 2012, 153, 1127–1131.

scholarly journals Altered expression profile of BAFF receptors on peripheral blood B lymphocytes in Graves’ disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Wang ◽  
Jinhui Huang ◽  
Aixia Zhang ◽  
Chen Fang ◽  
Qi Ma ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Expression Profile ◽  
Hashimoto’S Thyroiditis ◽  
B Lymphocyte ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Altered Expression ◽  
Autoimmune Thyroid ◽  
New Strategy

Abstract Background B lymphocyte activating factor (BAFF) is a growth factor regulating B lymphocytes survival and maturation. Serum BAFF levels were elevated in patients affected with autoimmune thyroid diseases (AITD), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). The aim of this study is to explore the association of expression levels of BAFF and its receptors with AITD. Methods Fifty-two GD patients, 39 Hashimoto’s thyroiditis (HT) patients and 23 healthy controls (HC) were recruited in this study. Serum BAFF levels were measured by ELISA. Expression of BAFF receptors, including BAFF receptor 3 (BR3) and transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI), on B lymphocytes were analyzed by flowcytometry. Effects of steroids on serum BAFF levels and expression of BR3 and TACI were also observed in 10 patients with Graves’ orbitopathy (GO) receiving steroids therapy. Results Serum BAFF levels were significantly elevated from 0.93 ± 0.24 ng/ml in HC to 1.18 ± 0.33 ng/ml in GD (P = 0.0027) and 1.02 ± 0.24 ng/ml in HT (P = 0.0331). BR3 expression on peripheral B lymphocytes were elevated in GD (mean MFI: 4.52 ± 2.06 in GD vs. 3.00 ± 0.87 in HC, P = 0.0015), while TACI expression on peripheral B lymphocytes were decreased in GD without significance (mean MFI: 7.96 ± 4.06 in GD vs. 9.10 ± 3.37 in HC, P = 0.1285). Expression of BR3 and TACI was not changed significantly in HT patients. Steroids significantly suppressed serum BAFF concentrations (from 1.18 ± 0.27 ng/ml to 0.97 ± 0.10 ng/ml, P = 0.0364) and BR3 expression in GO patients (mean MFI from 6.26 ± 4.91 to 4.05 ± 1.58, P = 0.0083). Conclusions Altered expression of BAFF and its receptor may mediate the autoimmunity in GD. Restoring the normal expression profile of receptors for BAFF could be a new strategy to treat GD.

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