Expression profile of interferon-gamma (IFN- γ) mRNA as diagnostic molecular signatures of Hashimoto's Thyroiditis

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.

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.


Author(s):  
Siti Nurul Hapsari ◽  
Sidarti Soehita

Hashimoto thyroiditis (chronic autoimmune thyroiditis) is the most common cause of hypothyroidism in iodine-sufficient areas of the world. This condition, however, can sometimes show hyperthyroidism. A 39-year-old femalewas admitted to hospital due to shortness of breath and tremor four hours before hospitalization. There were nausea, chestpain, cold chills, and palpitation. She was diagnosed with Hashimoto's thyroiditis and routinely received tyrosol,propranolol, and dexamethasone. Physical examination showed cervical mass, afebrile, blood pressure of 130/70 mmHg,pulse rate of 110 beats/minute and respiratory rate of 20 breaths/minute. Laboratory examinations showed WBC 7.53 x 109/L, Hb 11.0 g/dL and platelet count of 168 x 109/L. Chest X-Ray: negative for infiltrates. Several laboratory testswere performed, abnormal results were as follows: FT4 level of 2.96 ng/dL (increased), TSH level of 0.003 µIU/mL(decreased), anti-TPO (antithyroid microsomal antibody) level of 306 IU/ml (increased), and IgE level of 213.6 IU/mL(increased). Peripheral blood smear, coagulation test, serum electrolytes, liver function tests, renal function tests, urinalysis,CEA and Ca 125 were within normal limits. Thyroid ultrasound was performed and showed a benign lesion. Fine needleaspiration biopsy showed lymphocytic Hashimoto's thyroiditis. Echocardiography showed hyperthyroid heart disease. Dueto an increase of anti-TPO and FT4 levels, a decrease of TSH levels and lymphocytic thyroiditis from FNAB, this patient wasdiagnosed with a hyperthyroid phase of Hashimoto's thyroiditis. Thyroid function tests and thyroid antibody tests must bemonitored to distinguish between the hyperthyroid and hypothyroid phase of Hashimoto thyroiditis.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Stana Tokić ◽  
Mario Štefanić ◽  
Ljubica Glavaš-Obrovac ◽  
Sonja Jaman ◽  
Eva Novosadová ◽  
...  

Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disorder characterized by progressive thyroid failure. Th1 and Treg subset of CD4+ cells have been implicated in the pathogenesis; however, less is known about their respective roles across the spectrum of HT clinical presentations. To shed more light on CD4+ subsets role in HT, we investigated the mRNA expression levels of several Th1/Treg-associated transcription factors (T-bet/ETS1, HIF1α/BLIMP1/FOXP3) in peripheral blood T cells of 10 hypothyroid, untreated HT patients, 10 hypothyroid patients undergoing hormone replacement therapy, 12 euthyroid HT subjects, and 11 healthy controls by the qRT-PCR. Compared to euthyroid HT patients and controls, both hypothyroid (2.34-fold difference versus controls, P<0.01) and thyroxine-supplemented patients (2.5-fold, P<0.001) showed an increased FOXP3 mRNA expression in T cells. Similarly, mRNA expression levels of T-bet were upregulated in severely affected but not in euthyroid HT subjects (2.37-fold and 3.2-fold, hypothyroid and thyroxine-supplemented HT patients versus controls, resp., P<0.01). By contrast, no differences in mRNA expression levels of ETS1, BLIMP1, and HIF1α were observed across the study groups. In summary, severe but not euthyroid HT was associated with robust upregulation of T-bet and FOXP3 mRNA in peripheral T cells, independent of the thyroid hormone status but proportional to disease activity.


2019 ◽  
Vol 65 (6) ◽  
pp. 830-833 ◽  
Author(s):  
Roberto Vita ◽  
Valeria Cernaro ◽  
Salvatore Benvenga

SUMMARY OBJECTIVE Even though stress has been long known as a provocative factor for Graves’ disease, its relationship with Hashimoto's thyroiditis is more controversial. Studies on this topic are scanty. This paper aims to report a case of stress-induced Hashitoxicosis. RESULTS Here we report a case of Hashitoxicosis induced by a psychological stressful event in a 28-year-old woman with Hashimoto's thyroiditis. She had remained stably euthyroid for 12 years. She was first observed in April 2016, while euthyroid. She came back after 11 months because of fatigue and palpitations, in the absence of neck pain. Thyroid function tests revealed moderate thyrotoxicosis (undetectable TSH; FT4 36.94 pmol/L, normal values 9.0-24.46; FT3 13.50 pmol/L, normal values 3.07-6.14) with negative TSH-receptor antibodies. In the previous three months, she had experienced a psychological stressful event. Inflammatory markers were negative, and the white cell count was normal. Thyroid ultrasound revealed a modest increase in vascularization. Transient subclinical hypothyroidism ensued after seven weeks and spontaneously recovered. On the last visit, the patient was still on euthyroidism. (TSH 1.01 mU/L; FT4 9.22 pmol/L; FT3 3.98 pmol/L). We also performed HLA serotyping and genotyping. CONCLUSION This case demonstrates that, similarly to Graves’ disease, Hashitoxicosis can also be triggered by stressful life events.


2016 ◽  
Vol 50 (2) ◽  
pp. 55-61 ◽  
Author(s):  
Hakki Yilmaz ◽  
M. Cakmak ◽  
B. Ceydilek ◽  
C. Demir ◽  
A. Aktas

AbstractObjective. Interleukin-35 (IL-35), an interleukin-12 (IL-12) cytokine family member, is shown to be a potent immunosuppressive and anti-inflammatory cytokine. Inducible regulatory T cells (Tregs) produce IL-35 that mediates the immune inhibitory function of Tregs. Growing evidence revealed that upregulation of IL-35 expression may play a critical role in the prevention of autoimmune diseases in various experimental autoimmunity models and vice versa. Hashimoto’s thyroiditis (HT) is considered to be a Treg cell-related autoimmune disease with loss of self-tolerance. Methods. One hundred-twenty eight subjects, newly diagnosed hypothyroid HT patients [56 overt (Group 1), 72 subclinical hypothyroid (Group 2)] and 38 healthy controls (Group 3) were enrolled in the study. The levels of serum IL-35 were determined by enzyme-linked immunosorbent assay (ELISA). Results. Serum IL-35 levels were lower in the HT group when compared with subclinical HT group [304.5 (834.6) pg/ml vs. 636.1 (1542.0) pg/ml, p=0.004] and control cases [304.5 (834.6) pg/ml vs. 1064.7 (2526.8) pg/ml, p<0.001]. Serum IL-35 levels were inversely associated with thyroid stimulating hormone (TSH; rs=-0.396, p<0.001) and anti-thyroid peroxidase antibodies (TPOAb; rs=-0.571, p<0.001) in whole group. Serum IL-35 were negatively associated with TSH (rs=-0.264, p=0.003) and TPOAb (rs=-0.735, p<0.001) in patients with Hashimoto’s thyroiditis (Group 1 + Group 2). Conclusion. The results suggest that IL-35 may play a role in the pathogenesis of HT.


2014 ◽  
Vol 7 ◽  
pp. CPath.S13580 ◽  
Author(s):  
Monika Rathi ◽  
Faiyaz Ahmad ◽  
Satish Kumar Budania ◽  
Seema Awasthi ◽  
Ashutosh Kumar ◽  
...  

Introduction Hashimoto's thyroiditis is the most common form of acquired hypothyroidism. Fine needle aspiration cytology is one important tool in diagnosing Hashimoto's thyroditis, along with clinical, biochemical, immunological and ultrasonographical modalities. The present study examines cytological aspects of Hashimoto's thyroiditis along with their correlation with clinical, biochemical and immunological findings, whenever available. Materials and Methods This is a retrospective study of 50 cases of Hashimoto's thyroiditis. Cytological findings were reviewed and correlated with clinical, biochemical and immunological findings whenever available. Results The majority of the patients were middle-aged females, with a female to male ratio of 6.14:1. Most patients presented with diffuse thyromegaly (68%) and/or hypothyroidism (56.09%). The antibody profile was available in 22% of patients. Of these, anti-thyroid peroxidase antibodies were raised in 81.81% of patients and anti-thyroglobulin antibodies were raised in 63.63% of patients. In the present study, high lymphoid to epithelial cell ratio was seen in 78% of cases, and 74% of cases showed Hurthle cell change. Follicular atypia was seen in 36% of cases. Lymphoid follicle formation was seen in seen in 54% of cases. Follicular cell infiltration by lymphocytes, eosinophils and neutrophils was seen in 72%, 48% and 26% of cases, respectively. Plasma cells were seen in 18% of cases. Conclusion Thyroid function tests and immunological tests cannot diagnose all cases of Hashimoto's thyroiditis. Fine needle aspiration cytology continues to be a diagnostic tool of significance in diagnosing Hashimoto's thyroiditis. The presence of inflammatory cells, particularly lymphocytes and eosinophils, was detected in a significant proportion of cases.


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


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