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

2020 ◽  
Author(s):  
Xin Wang ◽  
Jinhui Huang ◽  
Aixia Zhang ◽  
Chen Fang ◽  
Qi Ma ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Expression Profile ◽  
Peripheral Blood ◽  
Hashimoto’S Thyroiditis ◽  
B Lymphocyte ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Altered Expression ◽  
Autoimmune Thyroid

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 investigate the association of expression of BAFF receptors on the peripheral blood B lymphocytes in addition to serum BAFF concentrations in patients affected with GD.Methods: Fifty-two GD patients, 39 Hashimoto’s thyroiditis (HT) patients and 23 healthy controls (HC) were recruited in this study. Serum BAFF levels and its receptors expression, including BAFF receptor 3 (BR3) and transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI), in AITD patients were compared to those in HC. In 10 patients with Graves’ orbitopathy (GO) receiving steroids therapy, effects of steroids on serum BAFF levels and expression of BR3 and TACI were observed.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.

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.

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 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 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.

scholarly journals Skewed expression profile of receptors for BAFF on peripheral blood B lymphocytes in Graves’ Disease

2020 ◽  
Author(s):  
Xin Wang ◽  
Jinhui Huang ◽  
Aixia Zhang ◽  
Chen Fang ◽  
Qi Ma ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Expression Profile ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Graves Disease ◽  
Normal Expression ◽  
New Strategy ◽  
Graves Orbitopathy ◽  
Infiltrating Lymphocytes ◽  
Altered Serum

Abstract Background Previous studies have demonstrated altered serum B lymphocyte activating factor (BAFF) level and expression of BAFF and BAFF receptor (BAFF-R) in thyroid infiltrating lymphocytes in Graves’ disease (GD) patients. The aim of the present study was to investigate expression of receptors for BAFF on the peripheral blood B lymphocytes in addition to serum BAFF concentrations. Methods Fifty-two GD patients and twenty-three healthy controls (HC) were recruited in this study. Serum BAFF concentrations were measure by ELISA. Expression of receptors for BAFF on peripheral blood B lymphocytes, including BAFF-R and transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI), was analyzed by flow cytometry. Serum BAFF levels, expression of BAFF-R and TACI on peripheral blood B lymphocytes were compared between GD and HC groups. Correlations between serum BAFF concentrations and thyroid function and thyrotropin receptor autoantibody (TRAb) titers were analyzed in GD patients. In 10 patients with Graves’ orbitopathy (GO) receiving steroids therapy, effects of steroids on serum BAFF levels and expression of BAFF-R and TACI were observed. Results Serum BAFF levels were significantly higher in GD patients (1.18 ± 0.33 ng/ml) than those in HC (0.93 ± 0.24 ng/ml, P = 0.0011). In GD patients, serum BAFF levels correlated positively with free thyroxine concentrations (Spearman r = 0.2460, P = 0.0394), but not TRAb titers (P = 0.4734). BAFF-R 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 < 0.0001), while TACI expression on peripheral B lymphocytes were decreased in GD (mean MFI: 7.96 ± 4.06 in GD vs 9.10 ± 3.37 in HC, P = 0.0331). Steroids significantly suppressed serum BAFF concentrations ( from 1.18 ± 0.27 ng/ml to 0.97 ± 0.10 ng/ml, P = 0.0364) and BAFF-R expression on peripheral blood B lymphocytes in GO patients (mean MFI from 6.26 ± 4.91 to 4.05 ± 1.58, P = 0.0083). Change of TACI expression on B lymphocytes was not statistically significant after steroids therapy. Conclusions Skewed expression profile of receptors for BAFF on B lymphocytes may mediate the autoimmunity in GD. Restoring the normal expression profile of receptors for BAFF could be a new strategy for treating and cueing GD.

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