scholarly journals Interferon-gamma Expression Profile as Diagnostic Signatures of Unexplained Infertility in Female Patients Suffer from Hashimoto's Thyroiditis

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.


2011 ◽  
Vol 55 (8) ◽  
pp. 628-631 ◽  
Author(s):  
Claudia Dutra Costantin Faria ◽  
Simone Ribeiro ◽  
Cristiane Kochi ◽  
Aryane Pereira Neves da Silva ◽  
Bruna Natalia Freire Ribeiro ◽  
...  

INTRODUCTION: Patients with Down syndrome (DS) often have elevated TSH (hypothalamic origin), which is called TSH neurosecretory dysfunction (TSH-nd). In these cases, there is slight elevation in TSH (5-15 µUI/mL), with normal free T4 and negative thyroid antibodies (AB). OBJECTIVE: To recognize the risk of progression to Hashimoto's thyroiditis (HT). SUBJECTS AND METHODS: We retrospectively analyzed 40 DS patients (mean age = 4.5 years), followed up for 6.8 years. RESULTS: HT was diagnosed in 9/40 patients, three early in monitoring, and six during evolution. In 31/40 patients, TSH-nd diagnosis remained unchanged over the years, with maximum TSH values ranging from 5 to 15 µUI/mL. In this group, free T4 also remained normal and AB were negative. There was a significant TSH reduction (p = 0.017), and normal TSH concentrations (< 5.0 µUI/mL) were observed in 29/31 patients, in at least one moment. No patient had TSH > 15 µUI/mL. CONCLUSION: DS patients with TSH-nd present low risk of progression to HT (10% for females and 6% for males).


1996 ◽  
Vol 105 (3) ◽  
pp. 523-528 ◽  
Author(s):  
R. A. AJJAN ◽  
P. F. WATSON ◽  
R. S. MCINTOSH ◽  
A. P. WEETMAN

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


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sabah Patel ◽  
Petra Krutilova ◽  
Janice L Gilden

Abstract Introduction: Congenital Thyroid hemi-agenesis is an uncommon clinical entity. We present a case highlighting the importance of awareness of this condition and the need to evaluate and manage co-existing hypothyroidism and risk of malignancy. Case: A 20 year old female known to have Hashimoto’s thyroiditis (non-adherent to levothyroxine), and hemi-agenesis of left lobe of thyroid gland, presented with right-sided thyroid enlargement. She was clinically euthyroid. Physical exam: enlarged right sided thyroid gland with palpable anterior cervical lymphadenopathy. Left lobe could not be palpated. TFTs were notable for TSH 4.98 uIU/ml (0.358-3.74) and Free T4 0.79 ng/dl (0.76-1.46) consistent with sub-clinical hypothyroidism while Anti TPO antibody was positive at 8332.8 U/mL (0 - 60). CBC negative for leukocytosis. US thyroid: left-sided thyroid agenesis with intact isthmus and enlargement of right lobe of the thyroid 7.7 cm x 1.6 cm x 2.6 cm with 2 sub-centimeter hypoechoic solid nodules and 2 enlarged lymph nodes 1.5 cm and 2.3 cm (not found in US thyroid 2 years ago) Levothyroxine was re-started. ENT evaluation determined that her lymphadenopathy was benign and consistent with Hashimoto’s thyroiditis. Subsequent TFTs improved. Discussion: Thyroid Gland embryogenesis occurs in the 4th week of fetal life. Subsequent abnormal bilobal differentiation of the thyroid gland is presumed to be the etiology of congenital hemi-agenesis. Its prevalence in several studies is estimated to be between 0.05-0.25%. It is symptomatic pre-dominantly in females and may have familial origin with vast majority of cases having left hemi-agenesis with intact isthmus. It is helpful to know that most symptomatic patients have compensatory hypertrophy of the remnant lobe. It is important to remember that compensatory enlargement of the remnant lobe in the setting of hypothyroidism may be a sign of insufficient endogenous thyroxine production and/or replacement. Although rarely symptomatic, hemi-thyroid remnant may need to be evaluated for co-existing hyperthyroidism, hypothyroidism, carcinoma and multinodular goiter among others, with hypothyroidism thought to be the most common. US thyroid is a useful modality to help guide the evaluation of patients with hemi-agenesis. Awareness of this congenital condition is key in preventing unnecessary evaluations and interventions. Non-resolving lymphadenopathy in Hashimoto’s thyroiditis must be evaluated for lymphoma, however, based on studies, no additional risk of malignancy was identified in patients with underlying thyroid hemi-agenesis. References: Y.H. Wu, R.O. Wein, B. Carter Thyroid hemiagenesis: a case series and review of the literature Am J Otolaryngol, 33 (3) (2012), pp. 299-302


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.


2018 ◽  
Vol 227 (4) ◽  
pp. e124
Author(s):  
Vardan Papoian ◽  
Jennifer E. Rosen ◽  
Wen Lee ◽  
Leonard Wartofsky ◽  
Erin A. Felger

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