Infiltration In Thyroid Tissue Research Articles

Identification and Preliminary Clinical Validation of Key Extracellular Proteins as the Potential Biomarkers in Hashimoto's Thyroiditis by Comprehensive Analysis.

Hashimoto's thyroiditis (HT) is an autoimmune disruption manifested by immune cell infiltration in thyroid tissue and the production of antibodies against thyroid-specific antigens, such as the thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb). TPOAb and TGAb are commonly used in clinical tests; however, handy indicators of the diagnosis and progression of HT are still scarce. Extracellular proteins are glycosylated and are likely to enter body fluids and become readily available and detectable biomarkers. Our research aimed to discover extracellular biomarkers and potential treatment targets associated with HT through integrated bioinformatics analysis and clinical sample validations. A total of 19 extracellular protein-differentially expressed genes (EP-DEGs) were screened by the GSE138198 dataset from the Gene Expression Omnibus (GEO) database and protein annotation databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE, and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Six key EP-DEGs (CCL5, GZMK, CXCL9, CXCL10, CXCL11, and CXCL13) were further validated in the GSE29315 dataset and the diagnostic curves were evaluated, which all showed high diagnostic accuracy (AUC > 0.95) for HT. Immune profiling revealed the correlation of the six key EP-DEGs and the pivotal immune cells in HT, such as CD8+ T cells, dendritic cells, and Th2 cells. Further, we also confirmed the key EP-DEGs in clinical thyroid samples. Our study may provide bioinformatics and clinical evidence for revealing the pathogenesis of HT and improving the potential diagnosis biomarkers and therapeutic strategies for HT.

The association between serum adenosine deaminase levels and Graves’ disease

BackgroundAdenosine deaminase (ADA) is essential for the differentiation and maturation of lymphocytes, while lymphocytes infiltration in thyroid tissue is a vital pathological feature of Graves’ disease (GD). The aim of the present study was to compare the concentration of ADA between healthy controls (HC) and patients with GD, and evaluate the association between ADA and GD.MethodsA total of 112 GD patients and 77 matched HC were enrolled in this study. Each participant was examined for thyroid hormones and autoantibodies, ADA concentration, and thyroid ultrasonography.ResultsSerum ADA levels in GD patients were significantly higher than that in HC subgroup (P < 0.001). In GD patients, serum ADA levels were positively associated with serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb) levels, and total thyroid gland volume (thyroid VolT) and negatively associated with serum thyroid-stimulating hormone receptor (TSH) levels (all P < 0.05). There were no similar correlations in the HC subgroup. Multiple linear regression analysis suggested that serum TSH, FT3, and ADA levels played an important role in serum TRAb levels.ConclusionsOur results demonstrated that serum ADA levels were closely associated with GD.

Metformin Reverses Hashimoto's Thyroiditis by Regulating Key Immune Events.

BackgroundHashimoto’s thyroiditis (HT) is a common autoimmune disease characterized by high levels of thyroid peroxidase antibody (TPOAb) and thyroid globulin antibody (TgAb) as well as infiltration of lymphocytes in thyroid. In recent years, metformin has been proven to be effective in a variety of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis.MethodsThis study systematically explored the therapeutic effect of metformin on HT and its underlying mechanism by comprehensively utilizing methods including animal model, in vitro cell culture and differentiation, mRNA sequencing and 16S rRNA sequencing.FindingsWe found that metformin indeed had a therapeutic effect on mice with HT mainly by reducing TgAb and lymphocyte infiltration in thyroid tissue. In addition, metformin also significantly suppressed the number and function of Th17 cells and M1 macrophages polarization in HT mice. Furthermore, metformin can inhibit the differentiation and function of Th17 in vitro. The results of mRNA sequencing of thyroid tissue illustrated that the therapeutic effect of metformin on HT was mainly achieved by regulating immune pathways. 16S RNA sequencing of the intestinal flora found that the intestinal flora of HT mice differs significantly from that of the normal mice and also were altered by metformin treatment.InterpretationThese experiments provided a preliminary theoretical basis for the clinical application of metformin in the treatment of HT.

Metformin Reverses Hashimoto's Thyroiditis by Regulating Key Immune Events

Background: Hashimoto's thyroiditis (HT) is a common autoimmune disease characterized by high levels of thyroid peroxidase antibody (TPOAb) and thyroid globulin antibody (TgAb) as well as infiltration of lymphocytes in thyroid. In recent years, metformin has been proven to be effective in a variety of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Methods: This study systematically explored the therapeutic effect of metformin on HT and its underlying mechanism by comprehensively utilizing methods including animal model, in vitro cell culture and differentiation, mRNA sequencing and 16S rRNA gene sequencing. Findings: We found that metformin indeed has a therapeutic effect on mice with HT mainly by reducing TgAb and lymphocyte infiltration in thyroid tissue. In addition, metformin also significantly inhibits the formation of Th17 cells and M1 macrophages in vivo. Furthermore, metformin can inhibit the differentiation and function of Th17 in vitro. The results of mRNA sequencing of thyroid tissue showed that the therapeutic effect of metformin on HT is mainly achieved by regulating immune disorders. 16S RNA sequencing of the intestinal flora found that the intestinal flora of HT mice differ significantly from that of the normal mice and also are altered by metformin treatment. Interpretation: This experiments provide a preliminary theoretical basis for the clinical application of metformin in the treatment of HT. Funding Statement: The present work was supported by grants from the National Natural Science Foundation of China (No.81873636 and No.81900710), Shanghai Natural Science Foundation (No.18ZR1433800). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All patients and healthy controls have signed informed consent. The study was approved by the ethical committees of Zhoupu Hospital and performed in accordance with relevant guidelines and regulations. All animal experiment procedures were approved by the Animal Ethics Committee of Fudan University.

Phenotypical Analysis of Lymphocytes with Suppressive and Regulatory Properties (Tregs) and NK Cells in the Papillary Carcinoma of Thyroid

The immune system seems to play a key role in preventing metastasis and recurrence of thyroid cancer. T regulatory lymphocytes (Tregs) and natural killer (NK) cells play an important role in the dysfunction of the host immune system in cancer patients. We investigated thyroid gland infiltration by Tregs and NK cells in patients with papillary thyroid cancer (PTC) and thyroid nodular goiter (TNG). The correlation between the extent of the disease and the lymphocytic infiltration of Tregs and NK cells was examined. A total of 65 patients with PTC, 25 with TNG, and 50 healthy controls were studied. Blood and tissue samples from 28 patients with PTC and 13 with TNG and blood samples from the healthy controls were analyzed for T4 (CD3(+)CD4(+)), T8 (CD3(+)CD8(+)), NK (CD3(-)CD16(+)CD56(+)), and CD4(+)CD25(+)CD127(-/low) Tregs by flow cytometry (FC). Tissue samples were also analyzed for Foxp3(+) Tregs by immunohistochemistry. Tregs showed greater infiltration in thyroid tissue of PTC patients compared with patients with TNG (P < 0.0009 for FC and P < 0.0001 for immunohistochemistry); FC analysis of blood samples showed no difference between the groups. Flow cytometry analysis showed significantly increased NK cells in PTC tissue compared with TNG tissue (P = 0.037), whereas blood samples showed no difference. CD4(+) and CD8(+) T cells did not differ in blood and tissue samples. Increased Tregs tissue infiltration was positively correlated with advanced disease stage (P < 0.0026), whereas NK infiltration was negatively correlated (P < 0.0041). Tregs and NK cells may be important regulators of thyroid cancer progression.

Influence of lymphocitic thyroiditis on prognostic outcome differentiated thyroid carcinoma

Thyroid carcinoma is rare malignant tumors. They are typically presented with slow progression and clinical course. Lymphocytic infiltration, including fagocytosis of neoplastic cells by macrophage plays an important role in preventing development of distant metastases. This paper sets the following objectives: Establish whether presence or absence of Hashimoto thyroiditis in differentiated thyroid carcinoma (DTC) is a favourable prognostic factor. The group under examination here are all newly diagnosed patients with differentiated thyroid carcinoma surgically treated at the Surgery Clinic in Podgorica from 2003. to 2010. A total of 125 patients, aged 11 to 79, were included in this research. The patients were divided in two groups, those with and those without lymphocytic infiltration. Both groups were mutually compared for their prognostic factors. For the identification of T and B lymphocytes, anti-CD 3 and anti-CD 20 antibodies were used. Student t-test was used for comparison of clinical and pathological parameters among groups, Hi square test for comparison of frequency, and Coxs regression model for time dependant variables as frequency of recurrence among groups with various stages of disease. Survival curve (Kaplan-Meier) is used for comparison of time dependant variables (survival, recurrence, death). The follow-up time ranges from 10 to 70 months in both groups of patients. presence of lymphocytic infiltration in thyroid tissue in patients with differentiated thyroid carcinoma is significant prognostic factor (P < 0.0001). But, absence of lymphocytic infiltration is a poor prognostic factor in patients with invasive extra thyroid tumours (P < 0.0001). Also, absence of lymphocytic infiltration is a poor prognostic factor for development of lymphogenic and hematogenic metastases. The presence of T or B lymphocytes and varying degree of their presence is not a significant prognostic factor (P < 0.0046). Patients without lymphocytic infiltration are significantly more numerous in the fourth stage of disease (P < 0.0001). There is no statistically significant difference in terms of the presence of T or B lymphocytes in the tissue. Chronic lymphocytic thyroidis hahshimoto is a favourable prognostic factor in our examined group (P < 0.0001). Local invasiveness and extrathyroid expansion is significantly smaller in the group of patients with the presence of lymphocytic infiltration (P < 0.0001). By means of univariate analysis, we found that factors with a significant impact on survival rate include age (P < 0.0001), size of tumour (P < 0.018), extrathyroid invasiveness (P < 0.0001), hematogenic metastases (P < 0.049). Lymphocytic infiltration is present in 81% of patients in their thyroid gland, and in 19% patients there are no lymphocytes in tissue. Limphocitic infiltration has a favourable influence on tumor variables. CONCLUSION. This research has shown that lymphocytes in tissue as part of Hashimoto thzroiditis have an effect on certain prognostic factors of differentiated thyroid carcinoma as size, smaller invasiveness and extrathyroid tumour growth and incidence of hematogenic metastases.

Immunological features of nonimmunogenic hyperthyroidism.

Blood lymphocyte subpopulations (Leu 4+ cells = pan-T cells, Leu 3a+ cells = helper/inducer cells, and Leu 2a+ cells = suppressor/cytotoxic cells), thyroid-stimulating immunoglobulins, microsomal antibodies and antibodies against thyroglobulin were determined in 10 patients with hyperthyroidism due to single autonomously functioning thyroid nodules (ATN), 11 patients with hyperthyroidism due to Graves' disease (GD) and in 20 normal subjects. Thyroidectomy was performed in 8 of the patients with ATN and in 6 of those with GD after 3 weeks of antithyroid drug treatment with methimazole. Lymphocytic infiltration of thyroid tissue, the amount of the various lymphocyte subsets (Leu 4+, Leu 3a+, and Leu 2a+ T cells as well as B+ B cells) in the thyroid gland, as well as the expression of the histocompatibility antigen HLA-DR on thyrocytes and intrathyroidal lymphocytes were examined. Blood Leu 4+ cells were reduced due to a lack of Leu 2a+ cells in patients with ATN and GD when compared to normal subjects. Thyroid-stimulating immunoglobulins were detected in all patients with ATN and GD, but in none of the normal subjects. Lymphocytic infiltration of thyroid tissue was present in patients with ATN and GD. The various lymphocyte subsets in the thyroid gland did not differ between the two patient groups. DR expression on thyrocytes was seen in 6 of the patients operated for ATN and in 5 of those who underwent surgery for GD. Infiltration with DR+-T lymphocytes was found in all thyroid glands investigated. Thus immunological findings usually classified as proof for the autoimmune origin of GD exist also in patients with ATN. An overlap in the pathogenetic background of both diseases seems possible.