scholarly journals Serum interferon-gamma (IFN- γ) and expression profile of IFN- γ provide diagnostic signatures of unexplained infertility in females with Hashimoto’s Thyroiditis.

Author(s):  
Nearmeen Rashad ◽  
Reham El Shabrawy ◽  
Ahmed Radwan ◽  
Reem Allam ◽  
Rehab Abdul Maksoud ◽  
...  
Author(s):  
Nearmeen M. Rashad ◽  
Reham Mohamed El Shabrawy ◽  
Ahmed M. Radwan ◽  
Reem M. Allam ◽  
Rehab S. Abdul-Maksoud ◽  
...  

Diagnosis of unexplained infertility (UEI) is made by exclusion and a relatively common problem that affects couples worldwide. Unfortunately, it is a not uncommon for females to suffer from Hashimoto's thyroiditis (HT). Interferon-gamma (IFN- γ) has a central key role in HT and in the ability to conceive. We aimed to estimate serum IFN- γ level and its expression profile in Egyptian women with HT and assess their possible association with UEI. In this study, we examined 120 women with HT. We evaluated fertility in all patients; female patients who suffer from UEI were detected. Diagnosis of HT was based on the clinical data and the laboratory measures, enzyme-linked immunosorbent assay was used to measure serum IFN- γ, and the expression of IFN-γ messenger ribonucleic acid (mRNA) was assayed by real-time polymerase chain reaction (PCR). According to the results of this study, 37.5 % of the studied females who suffered from HT were diagnosed with UEI. The serum level of IFN-γ and its gene expression showed a significant positive correlation with thyroid-stimulating hormone (TSH) and thyroid autoantibodies. However, a negative correlation was found with anti-müllerian hormone (AMH), free T4 (FT3), and free T4 (FT4). Analysis by linear regression revealed that TSH and FT3 were associated with serum level of IFN-γ; while FT3 was associated with IFN-γ gene expression. We concluded that both are valued markers in diagnosing UEI in female patients suffering from HT.


2021 ◽  
Vol 30 (2) ◽  
pp. 117-123
Author(s):  
Nearmeen M. Rashad ◽  
Reham M. El Shabrawy ◽  
Shereen M. El Shabrawy ◽  
Hassan M. Hassanin

Background: Hashimoto's thyroiditis (HT) is a T cell-mediated autoimmune disease that primarily affects females. IFN- γ is a critical cytokine that has been related to the pathogenesis of HT. Objectives: We aimed to evaluate serum and expression levels of interferon-gamma (IFN- γ) in Egyptian women with HT and to assess the association between serum and expression levels of IFN- γ with clinical and laboratory characteristics of HT. Methodology: This case-control study included 120 women with HT and 70 controls. IFN- γ mRNA expression was analyzed using real-time polymerase chain reaction. Serum IFN- γ was measured using enzyme-linked immunosorbent assay. Results: Serum IFN- γ level and the level of IFN- γ mRNA are both sensitive and specific to be used as diagnostic markers for HT with cut off values of 28.57 pg/ml and 3.55 respectively. Both showed a significant positive correlation with TPO-Ab and Tg-Ab, obesity indices, dyslipidemia, and TSH, while they have a negative correlation with FT3, FT4. Conclusions: Serum IFN- γ level and the level of IFN- γ mRNA are both sensitive and specific to be used as diagnostic markers for HT, significantly correlated with thyroid autoantibodies and thyroid function tests.


1994 ◽  
Vol 141 (2) ◽  
pp. 309-315 ◽  
Author(s):  
R Paschke ◽  
F Schuppert ◽  
M Taton ◽  
T Velu

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


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A845-A845
Author(s):  
Yedi Cao ◽  
Zhijing Song ◽  
Yan Gong ◽  
Keli Zhao ◽  
Xue Zhao ◽  
...  

Abstract Objectives: Elevation of anti-thyroglobulin antibodies that are primarily IgG isotype is a hallmark of Hashimoto’s thyroiditis (HT). As for IgG,it bears two conserved repertoire of N-linked glycans attached to its crystallizable fragment (Fc) at the 297 asparagine residue (Asn297). In our previous study, we found that serum TgAb IgG from HT patients exhibits higher glycosylation levels than those observed from healthy controls. Previous studies confirmed that imbalance of Th1/Th2 and Th17/Treg leading to altered immune microenvironment with elevation of certain cytokines was found in the thyroid tissue of HT, including IFN-γ, TNF-α, IL-21, IL-17A, IL-6, BAFF, APRIL. Thus, the aim of our study was to investigate the influence of the elevated cytokines on the differentiation process of B cells and the glycosylation levels of IgG. Methods: We formed a two-phase culture system in vitro to promote B cells to differentiate to antibody-secreting cells (ASCs). In the process of cell culture, B cells were co-cultured with cytokines as followed: IFN-γ, TNF-α, IL-21, IL-17A, IL-6, BAFF and APRIL. Flow cytometry was performed to identify the percentage of plasmablasts (CD38+CD27high) and plasma cells (CD20-CD138+). ELISA was used to measure the yield of IgG in culture supernatants. The glycosylation levels of secreted IgG under different stimulation conditions were detected by lectin microarray. Results: We found that IL-21, TNF-α and BAFF can significantly promote the differentiation of B cells into ASCs in vitro culture system, and augment the production of IgG to over 4-fold. In addition, cytokines affected the glycosylation modification profile of IgG diversely: 1) IL-21, IL-17A, TNF-α, BAFF significantly increased the glycosylation level of sialic acid of total IgG; 2) IFN-γ significantly increased the level of galactose; 3) IL-21, IL-17A, IFN-γ, BAFF, and APRIL significantly increased the level of mannose; 4) IL-6 significantly decreased the level of sialic acid, galactose and mannose; 5) IL-17A, IFN-γ, TNF-α, BAFF significantly increased the level of GalNAc that was a component of O-Glycan,which only exists in the hinge region of IgG3 subclass. Conclusions: The abnormally elevated cytokines in microenvironment participated in the regulation of B cell terminal differentiation process and glycosylation level of IgG, thereby involving in the pathogenesis of AITD.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Wang ◽  
Jinhui Huang ◽  
Aixia Zhang ◽  
Chen Fang ◽  
Qi Ma ◽  
...  

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.


Author(s):  
Hajar VASEGHI ◽  
Fatemeh ESFAHANIAN ◽  
Zohreh JADALI

Background: The role of T cells in the pathogenesis of Hashimoto’s thyroiditis is well established, whereas the precise and likely the overlapping contributions of different T-cell subpopulations to thyroid injury are less understood. The purpose of this study was to assess the expression pattern of two lineage determining transcription factors, T-bet and GATA-3 that regulate differentiation of T cells into Th1 or Th2 cell fates, respectively. Moreover, the mRNA expression and plasma concentration of Th1(IFN-γ) and Th2(IL-4) cytokines were analyzed. Methods: In this case-control study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the expression patterns of various transcripts in 20 patients (in Endocrinology Clinic, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran, in 2015) with Hashimoto’s thyroiditis (HT) and 22 healthy controls. Plasma IL-4 and IFN-γ concentrations were also measured using enzyme-linked immunosorbent assay. Results: T-bet gene expression was significantly lower in patients compared to healthy controls (P=0.014). The expression of IL-4 mRNAs was significantly increased in the peripheral blood mononuclear cells from patients as compared to normal controls (P=0.001). In addition, a marked increase in plasma IL-4 levels were observed in patient group compared to controls (P=0.043). Conclusion: Altered balance between Th1 and Th2 related transcription factors and cytokines may be implicated in the pathogenesis of Hashimoto’s thyroiditis.


2020 ◽  
Author(s):  
Xin Wang ◽  
Jinhui Huang ◽  
Aixia Zhang ◽  
Chen Fang ◽  
Qi Ma ◽  
...  

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.


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