MACROPHAGE-LYMPHOCYTE INTERACTION IN GRAVES' DISEASE AND HASHIMOTO'S THYROIDITIS

ABSTRACT The formation of macrophage-lymphocyte rosettes was studied in lymphocyte cultures from patients with Graves' disease, Hashimoto's thyroiditis, other thyroid diseases and control subjects; the cultures were incubated with normal human thyroid and other non-specific antigens. At the end of incubation, the cell pellets were smeared on slides, stained with Wright's stain and the number of rosettes determined under the microscope. The membrane immunofluorescence technique was employed to identify whether the surrounding lymphocytes were T- or B-lymphocytes. In Graves' disease and Hashimoto's thyroiditis, the mean percentages of rosette formation with crude thyroid antigen were 0.98 ± 0.22 % (mean ± sem), and 1.15 ± 0.25 %, respectively. These values were significantly higher than those of control lymphocytes (0.03 ± 0.02 %). Lymphocytes from other thyroid diseases also gave higher values than controls. Kidney antigen, used as a control antigen, gave negative results in Graves' disease and other thyroid diseases, but in Hashimoto's thyroiditis, the mean percentage was of borderline significance. In the direct immunofluorescent staining study using fluorescein-conjugated goat anti-human Ig determinants, including the Fab fraction of anti-human IgG, it appeared that both B- and T-lymphocytes were involved in the rosettes, although B-lymphocytes were more numerous. These results indicate that in patients with Graves' disease and Hashimoto's thyroiditis, a probable immune reaction with thyroid antigen can be demonstrated by macrophage-lymphocyte rosette formation.

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Impact of the serum thyroglobulin concentration on the diagnostics of benign and malignant thyroid diseases

Nuklearmedizin ◽

10.1055/s-0038-1632259 ◽

2000 ◽

Vol 39 (05) ◽

pp. 133-138 ◽

Cited By ~ 4

Author(s):

W. Dembowski ◽

H.-J. Schroth ◽

K. Klinger ◽

Th. Rink

Keyword(s):

Hashimoto’S Thyroiditis ◽

Thyroid Volume ◽

Nodular Goiter ◽

Thyroid Diseases ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Normal Range ◽

Serum Thyroglobulin ◽

Diffuse Goiter ◽

Hyperthyroid Patients

Summary Aim of this study is to evaluate new and controversially discussed indications for determining the thyroglobulin (Tg) level in different thyroid diseases to support routine diagnostics. Methods: The following groups were included: 250 healthy subjects without goiter, 50 persons with diffuse goiter, 161 patients with multinodular goiter devoid of functional disorder (108 of them underwent surgery, in 17 cases carcinomas were detected), 60 hyperthyroid patients with autonomously functioning nodular goiter, 150 patients with Hashimoto’s thyroiditis and 30 hyperthyroid patients with Graves’ disease. Results: The upper limit of the normal range of the Tg level was calculated as 30 ng Tg/ml. The evaluation of the collective with diffuse goiter showed that the figure of the Tg level can be expected in a similar magnitude as the thyroid volume in milliliters. Nodular tissue led to far higher Tg values then presumed when considering the respective thyroid volume, with a rather high variance. A formula for a rough prediction of the Tg levels in nodular goiters is described. In ten out of 17 cases with thyroid carcinoma, the Tg was lower than estimated with thyroid and nodular volumes, but two patients showed a Tg exceeding 1000 ng/ml. The collective with functional autonomy had a significantly higher average Tg level than a matched euthyroid group being under suppressive levothyroxine substitution. However, due to the high variance of the Tg values, the autonomy could not consistently be predicted with the Tg level in individual cases. The patients with Hashimoto’s thyroiditis showed slightly decreased Tg levels. In Graves’ disease, a significantly higher average Tg level was observed compared with a matched group with diffuse goiter, but 47% of all Tg values were still in the normal range (< 30 ng/ml). Conclusion: Elevated Tg levels indicate a high probability of thyroid diseases, such as malignancy, autonomy or Graves’ disease. However, as low Tg concentrations cannot exclude the respective disorder, a routine Tg determination seems not to be justified in benign thyroid diseases.

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

Acta Endocrinologica ◽

10.1530/eje.1.01906 ◽

2005 ◽

Vol 152 (5) ◽

pp. 703-712 ◽

Cited By ~ 15

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.

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

Cellular Physiology and Biochemistry ◽

10.1159/000487870 ◽

2018 ◽

Vol 45 (5) ◽

pp. 1787-1796 ◽

Cited By ~ 8

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.

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

International Journal of Endocrinology ◽

10.1155/2019/7429187 ◽

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.

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The role of Fas-mediated apoptosis in thyroid disease

Acta Endocrinologica ◽

10.1530/eje.0.1440561 ◽

2001 ◽

pp. 561-568 ◽

Cited By ~ 26

Author(s):

M Andrikoula ◽

A Tsatsoulis

Keyword(s):

Thyroid Disease ◽

Hashimoto’S Thyroiditis ◽

Thyroid Diseases ◽

Current Evidence ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Thyroid Cell ◽

Thyroid Cells ◽

Soluble Fas

Recent evidence has emphasized the importance of apoptosis in the maintenance of tissue homeostasis and the pathogenesis of malignant and immune diseases. Autoimmune thyroid diseases such as Hashimoto's thyroiditis and Graves' disease, as well as other autoimmune endocrine diseases, have been associated with dysregulation of apoptotic signaling pathways. In particular, dysfunction of the Fas apoptotic pathway or production of soluble factors including soluble Fas and soluble Fas ligand may be involved in the pathogenesis of these disorders. On the other hand, malignant thyroid cells may avoid Fas-mediated suicide possibly by expression of inhibitors of apoptosis and evade the immune system by inducing apoptosis on infiltrating lymphocytes. The delicate balance between cell proliferation and cell death through the Fas pathway may also play an important role in the control of thyroid cell mass and goitrogenesis. This review analyzes the current evidence on the role of Fas-mediated apoptosis in the pathogenesis of thyroid diseases including Hashimoto's thyroiditis, Graves' disease, thyroid cancer and goiter. However, the exact mechanisms involved in the regulation of apoptosis in thyroid disease remain unclear. Further investigation is needed.

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Intrathyroidal cytokine gene expression profiles in autoimmune thyroiditis

Journal of Endocrinology ◽

10.1677/joe.0.1410309 ◽

1994 ◽

Vol 141 (2) ◽

pp. 309-315 ◽

Cited By ~ 64

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

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Thyroid antigen-induced leukocyte procoagulant activity: a novel approach to the study of cell-mediated immunity in graves' disease and hashimoto's thyroiditis

Journal of Steroid Biochemistry ◽

10.1016/0022-4731(84)90967-1 ◽

1984 ◽

Vol 20 (6) ◽

pp. 1643

Author(s):

Jacques How ◽

A.W. Thomson ◽

J.I. Milton ◽

R.M. Scott ◽

P.P. Bewsher ◽

...

Keyword(s):

Hashimoto’S Thyroiditis ◽

Procoagulant Activity ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Cell Mediated Immunity ◽

Novel Approach ◽

Thyroid Antigen

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

BMC Endocrine Disorders ◽

10.1186/s12902-021-00752-3 ◽

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

ISRN Endocrinology ◽

10.1155/2013/673146 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 4

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.

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