Evaluation of APRIL in serum of patients with Hashimoto’s Thyroiditis

Hashimoto’s thyroiditis (HT) is an autoimmune and inflammatory disease in which antibodies are directed against the thyroid gland leading to chronic inflammation and hypothyroidism. The autoimmunity against thyroid antigens can be associated to genetic background and environmental factors. Thyroid peroxidase (TPO) and thyroglobulin (TG) are the major autoantigens for characterizing the disease. HT is related to the activation of autoreactive CD4+ T cells, CD8+ cytotoxic T cells and antithyroid antibody producing-B cells. Among several cytokines related to the pathogenesis of HT, a proliferation-inducing ligand (APRIL) has been studied in the context of the establishment and/or maintenance of autoimmune diseases. The role of APRIL in the pathogenesis of HT is still poorly understood. Therefore, the present study aimed to compare APRIL serum concentration in HT patients and healthy donors by ELISA. We observed a significant decrease in APRIL concentration in HT patients when compared to the control group, and a positive correlation between APRIL level and age. Our results suggest that the APRIL molecule can compose the cytokine profile along the inflammatory response in HT, however, other investigations should be proposed to understand its molecular mechanisms via specific receptors and other regulatory loops.

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LncRNA profile in Hashimoto’s thyroiditis and potential function of NONHSAT079547.2

Journal of Molecular Endocrinology ◽

10.1530/jme-19-0239 ◽

2020 ◽

Vol 64 (4) ◽

pp. 259-270

Author(s):

Jingyi Luo ◽

Tingting Liu ◽

Weiping Teng

Keyword(s):

T Cells ◽

Real Time ◽

Potential Function ◽

Real Time Pcr ◽

Hashimoto’S Thyroiditis ◽

Molecular Mechanisms ◽

Hashimoto's Thyroiditis ◽

Control Group ◽

Thyroid Peroxidase ◽

Transcriptional Level

Hashimoto’s thyroiditis (HT) is a common organ-specific autoimmune disease, which develops in 0.3–1.5/1000 subjects annually. The aims of this study were to determine the lncRNA profile in peripheral blood CD4+ T cells from HT patients and then to characterize the potential function of NONHSAT079547.2. A total of 37 HT patients and 50 sex- and age-matched healthy controls were enrolled for high-throughput sequencing. Another 43 HT patients and 50 sex- and age-matched controls were enrolled for validation via real-time PCR. Flow cytometry and CCK8 assays were used to measure cell apoptosis and growth levels. Western blotting was used for measuring the expression of growth- and apoptosis-associated proteins. IL-17 serum concentration and transcriptional level in CD4+ T cells of participants were detected by ELISA and real-time PCR, respectively. The mechanism of competitive endogenous RNA was determined using real-time PCR, ELISA, RNA immunoprecipitation, and dual-luciferase assays in Jurkat cells. A total of 7564 significantly differentially expressed lncRNAs were found, of which 3913 lncRNAs were upregulated and 3651 lncRNAs were downregulated in HT group when compared to control group. NONHSAT079547.2 was significantly upregulated in HT patients and was positively correlated with serum thyroid peroxidase antibody level. Further studies confirmed that NONHSAT079547.2 could promote cell growth and control IL-17 expression and secretion via the NONHSAT079547.2/miR-4716-5p/IL-17 axis.This is the first study to describe the lncRNA profile in CD4+ T cells of HT patients. The studies on the function of NONHSAT079547.2 might elucidate the underlying molecular mechanisms and represent potential biomarkers for HT.

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Current Concepts in Endocrinology for Clinicians and Medical Students. Hashimoto’s Thyroiditis: clinical and subclinical thyroid dysfunction

Revista Científica da Faculdade de Medicina de Campos ◽

10.29184/1980-7813.rcfmc.224.vol.13.n2.2018 ◽

2018 ◽

Vol 13 (2) ◽

pp. 38-42

Author(s):

Paulo Travassos Neto

Keyword(s):

T Cells ◽

Hashimoto’S Thyroiditis ◽

Genetic Background ◽

Thyroid Dysfunction ◽

Cytotoxic T Cells ◽

Hormone Replacement ◽

Hashimoto's Thyroiditis ◽

Thyroid Peroxidase ◽

Antithyroid Antibody ◽

Thyroid Hormone Replacement

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Salivary gland function in women with Hashimoto’s thyroiditis without xerostomia and the correlation with auto-thyroid antibodies

Nuklearmedizin ◽

10.1055/a-1204-9748 ◽

2020 ◽

Author(s):

Xiao-an Pang ◽

Zhi-xiao Wei ◽

Jun-hong Li ◽

Xiao-qi Pang

Keyword(s):

Salivary Gland ◽

Hashimoto’S Thyroiditis ◽

Thyroid Stimulating Hormone ◽

Hashimoto's Thyroiditis ◽

Control Group ◽

Thyroid Peroxidase ◽

Thyroid Autoantibody ◽

Submandibular Glands ◽

Quantitative Parameters ◽

Salivary Function

Abstract Background Hashimoto’s thyroiditis (HT) may cause salivary dysfunction in patients resulting in xerostomia, but little is known about changes in salivary function in patients with no obvious dry mouth symptoms. In this study we assessed salivary function in women with HT, who had not experienced xerostomia and, for the first time, evaluated the effects of thyroid auto-antibodies on this function. Methods Sixty consecutive subjects were included, comprising 32 women (mean age, 36 ± 12 years) diagnosed with HT accompanied by differentiated thyroid cancer (DTC) in the study group (HT group), along with a control group (DTC group) of 28 women (mean age, 40 ± 12 years) diagnosed with DTC only. Salivary gland scintigraphy was used to assess salivary function with the semi-quantitative parameters of maximum absorption ratio and maximum secretion ratio, the decrease of which indicate impaired salivary function. Moreover, the HT and DTC groups were divided into four subgroups (Anti– HT, Anti+ HT, Anti– DTC, and Anti+ DTC), based on the presence of anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb). Finally, salivary gland semi-quantitative parameters were correlated with levels of thyroid-stimulating hormone (TSH), TGAb, and TPOAb in the HT and DTC groups. Results None of the semi-quantitative parameters examined in parotid or submandibular glands differed significantly between the HT and DTC groups. However, the maximum secretion ratio for the parotid and submandibular glands were significantly different in the subgroup comparison (p < 0.05). Furthermore, the TgAb, TPOAb, and TSH values correlated significantly with salivary excretive function (p ≤ 0.05). Conclusion Women with HT without xerostomia may not have salivary functional impairment during hypothyroidism. Serum thyroid autoantibody and TSH levels may mainly influence salivary excretive function but not uptake function.

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Dysregulated Interleukin -33/ST2 Pathway Perpetuates Chronic Inflammation in Hashimoto’s Thyroiditis

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190226164309 ◽

2019 ◽

Vol 19 (7) ◽

pp. 1012-1021 ◽

Cited By ~ 1

Author(s):

Xuan Wang ◽

Xiaoqing Shao ◽

Xinhao Liu ◽

Qiu Qin ◽

Jian Xu ◽

...

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Western Blot ◽

Chronic Inflammation ◽

Hashimoto’S Thyroiditis ◽

Thyroid Tissue ◽

Hashimoto's Thyroiditis ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Interleukin 33

Objective: Hashimoto’s Thyroiditis (HT) is an autoimmune disease, characterized by chronic inflammation of the thyroid gland with unknown etiologies. Recently, interleukin-33/ST2 (IL- 33/ST2) pathway reveals its participation in the process of several autoimmune diseases. In this study, the role of IL-33/ST2 pathway in the development of HT is investigated. Methods: The levels of plasma IL-33, sST2 and the frequency of circulating CD4+ST2L+T cells in 30 HT patients and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry respectively. The mRNA expressions of related molecules in IL-33/ST2 pathway in thyroid tissues (12 HT patients and 10 controls) were detected by real-time quantitative PCR (RTqPCR). The protein expressions of IL-33 and ST2 were determined by Western blot and immunohistochemistry staining. Results: The mRNA expressions of plasma IL-33 and sST2 were elevated in HT patients, with an increased ratio of IL-33/sST2. The number of CD4+ST2L+ T cells in PBMCs of HT group was significantly increased when compared to the control group (CON) by Flow cytometry assay. MRNA Expression of IL-33 and ST2 in thyroid tissue and the level of IL-1β and IL-18 were significantly upregulated in HT patients, while IL-5 was down-regulated in HT patients, compared to CON. The expression of IL-1β and IL-18 were positively correlated with the expression of IL-33. Results of western blot and immunohistochemical staining were consistent with qPCR. Conclusion: IL-33/ST2 pathway participates in HT via affecting the production of inflammatory cytokines.

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The Link between Graves’ Disease and Hashimoto’s Thyroiditis: A Role for Regulatory T Cells

Endocrinology ◽

10.1210/en.2007-1024 ◽

2007 ◽

Vol 148 (12) ◽

pp. 5724-5733 ◽

Cited By ~ 69

Author(s):

Sandra M. McLachlan ◽

Yuji Nagayama ◽

Pavel N. Pichurin ◽

Yumiko Mizutori ◽

Chun-Rong Chen ◽

...

Keyword(s):

T Cells ◽

Antibody Response ◽

Hashimoto’S Thyroiditis ◽

Lymphocytic Infiltration ◽

Hashimoto's Thyroiditis ◽

Thyroid Peroxidase ◽

Graves Disease ◽

Wild Type ◽

Treg Depletion ◽

A Subunit

Hyperthyroidism in Graves’ disease is caused by thyroid-stimulating autoantibodies to the TSH receptor (TSHR), whereas hypothyroidism in Hashimoto’s thyroiditis is associated with thyroid peroxidase and thyroglobulin autoantibodies. In some Graves’ patients, thyroiditis becomes sufficiently extensive to cure the hyperthyroidism with resultant hypothyroidism. Factors determining the balance between these two diseases, the commonest organ-specific autoimmune diseases affecting humans, are unknown. Serendipitous findings in transgenic BALB/c mice, with the human TSHR A-subunit targeted to the thyroid, shed light on this relationship. Of three transgenic lines, two expressed high levels and one expressed low intrathyroidal A-subunit levels (Hi- and Lo-transgenics, respectively). Transgenics and wild-type littermates were depleted of T regulatory cells (Treg) using antibodies to CD25 (CD4+ T cells) or CD122 (CD8+ T cells) before TSHR-adenovirus immunization. Regardless of Treg depletion, high-expressor transgenics remained tolerant to A-subunit-adenovirus immunization (no TSHR antibodies and no hyperthyroidism). Tolerance was broken in low-transgenics, although TSHR antibody levels were lower than in wild-type littermates and no mice became hyperthyroid. Treg depletion before immunization did not significantly alter the TSHR antibody response. However, Treg depletion (particularly CD25) induced thyroid lymphocytic infiltrates in Lo-transgenics with transient or permanent hypothyroidism (low T4, elevated TSH). Neither thyroid lymphocytic infiltration nor hypothyroidism developed in similarly treated wild-type littermates. Remarkably, lymphocytic infiltration was associated with intermolecular spreading of the TSHR antibody response to other self thyroid antigens, murine thyroid peroxidase and thyroglobulin. These data suggest a role for Treg in the natural progression of hyperthyroid Graves’ disease to Hashimoto’s thyroiditis and hypothyroidism in humans.

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Clinical Significance of Diffusely Increased Uptake of 68Ga-FAPI in Thyroid Gland

Frontiers in Medicine ◽

10.3389/fmed.2021.782231 ◽

2021 ◽

Vol 8 ◽

Author(s):

Huipan Liu ◽

Xiao Yang ◽

Lin Liu ◽

Lei Lei ◽

Li Wang ◽

...

Keyword(s):

Thyroid Gland ◽

Clinical Significance ◽

Hashimoto’S Thyroiditis ◽

Checkpoint Inhibitors ◽

Standardized Uptake Value ◽

Hashimoto's Thyroiditis ◽

Control Group ◽

Thyroid Peroxidase ◽

Chronic Thyroiditis ◽

Serum Tsh

Purpose: To determine the clinical significance of diffuse uptake of 68Ga-FAPI in the thyroid.Methods: From January 2020 to September 2021, all subjects with diffuse thyroid uptake in 68Ga-FAPI PET/CT were investigated in our hospital, and compared with the age and sex matched control group. The 68Ga-FAPI uptake in the thyroid gland was analyzed semi-quantitatively using the maximum standardized uptake value (SUVmax), and regression analysis was used to analyze the correlation between available serum thyroid stimulating hormone (TSH) and thyroid peroxidase antibody (TPOAb).Results: Among 815 subjects, 39 subjects were found diffuse FAPI uptake in thyroid gland; 11 subjects refused further examination; a total of 28 subjects were included in the analysis, and 27 subjects were diagnosed with chronic thyroiditis (including 20 subjects with Hashimoto's thyroiditis), 3 subjects with Grave's disease, 3 subjects with only serum TSH elevated, and 1 subject with malignant of thyroid and thyroiditis. The SUVmax of 27 subjects with thyroiditis was 5.75 ± 5.45. No significant correlation was found between the SUVmax and the level of serum TSH (P = 0.389) or TPOAb (P = 0.426).Conclusion: The incidentally discovered diffusely increased 68Ga-FAPI uptake in the thyroid gland is mostly related to chronic lymphocytic (Hashimoto's) thyroiditis. 68Ga-FAPI uptake level correlated neither with the degree of hypothyroidism nor with the titer of TPOAb. In addition, immune-related thyroiditis with immune checkpoint inhibitors may be accidentally found on 68Ga-FAPI, which may be helpful in facilitate timely intervention.

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Altered balance of immunoregulatory T lymphocyte subsets in autoimmune thyroid diseases

Acta Endocrinologica ◽

10.1530/acta.0.1050200 ◽

1984 ◽

Vol 105 (2) ◽

pp. 200-204 ◽

Cited By ~ 10

Author(s):

Takashi Misaki ◽

Junji Konishi ◽

Yasuhiro Iida ◽

Keigo Endo ◽

Kanji Torizuka

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Hashimoto’S Thyroiditis ◽

Mononuclear Cells ◽

Cytotoxic T Cells ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Autoimmune Thyroid Diseases ◽

Autoimmune Thyroid ◽

Significant Difference

Abstract. Three monoclonal antibodies recognizing cell surface antigens of total peripheral (OKT3), helper/inducer (OKT4) and suppressor/cytotoxic (OKT8) T lymphocytes were used by an indirect immunofluorescence technique to enumerate peripheral T lymphocytes in 25 patients with Graves' disease (including 4 euthyroid Graves' patients), 16 patients with Hashimoto's thyroiditis and 22 normal controls. Total lymphocyte count and percentages of overall T and helper/inducer T cells among peripheral lymphocytes in these conditions showed no significant difference from those of the controls. Percentage of suppressor/cytotoxic T cells, however, was decreased in Graves' disease patients with or without hyperthyroidism. The ratio of helper/inducer T cells to suppressor/cytotoxic T cells was increased in Graves' disease population and slightly increased in hypothyroid Hashimoto's thyroiditis patients. The ratio correlated with the mitogenic response of peripheral mononuclear cells to phytohaemagglutinin, but not with the serum levels of thyroid hormones nor with the titres of thyroid autoantibodies. These findings are in accordance with the results of previous functional studies and indicate possible defects in suppressor T lymphocytes in autoimmune thyroid disease.

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Vitamin D Treatment in Patients with Hashimoto’s Thyroiditis may Decrease the Development of Hypothyroidism

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000269 ◽

2016 ◽

Vol 86 (1-2) ◽

pp. 9-17 ◽

Cited By ~ 3

Author(s):

Bekir Ucan ◽

Mustafa Sahin ◽

Muyesser Sayki Arslan ◽

Nujen Colak Bozkurt ◽

Muhammed Kizilgul ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Hashimoto’S Thyroiditis ◽

Healthy Control Group ◽

Hashimoto's Thyroiditis ◽

Control Group ◽

Endocrine Society ◽

Thyroid Autoantibody ◽

Healthy Control ◽

The Mean

Abstract.The relationship between Hashimoto’s thyroiditis and vitamin D has been demonstrated in several studies. The aim of the present study was to evaluate vitamin D concentrations in patients with Hashimoto’s thyroiditis, the effect of vitamin D therapy on the course of disease, and to determine changes in thyroid autoantibody status and cardiovascular risk after vitamin D therapy. We included 75 patients with Hashimoto’s thyroiditis and 43 healthy individuals. Vitamin D deficiency is defined as a 25-hydroxy vitamin D (25(OH)D3) concentration less than 20ng/mL. Vitamin D deficient patients were given 50.000 units of 25(OH)D3 weekly for eight weeks in accordance with the Endocrine Society guidelines. All evaluations were repeated after 2 months of treatment. Patients with Hashimoto’s thyroiditis had significantly lower vitamin D concentrations compared with the controls (9.37±0.69 ng/mL vs 11.95±1.01 ng/mL, p < 0.05, respectively). Thyroid autoantibodies were significantly decreased by vitamin D replacement treatment in patients with euthyroid Hashimoto’s thyroiditis. Also, HDL cholesterol concentrations improved in the euthyroid Hashimoto group after treatment. The mean free thyroxine (fT4) concentrations were 0.89±0.02 ng/dL in patients with Hashimoto’s thyroiditis and 1.07±0.03 ng/dL in the healthy control group (p < 0.001). The mean thyroid volumes were 7.71±0.44 mL in patients with Hashimoto’s thyroiditis and 5.46±0.63 mL in the healthy control group (p < 0.01). Vitamin D deficiency is frequent in Hashimoto’s thyroiditis and treatment of patients with this condition with Vitamin D may slow down the course of development of hypothyroidism and also decrease cardiovascular risks in these patients. Vitamin D measurement and replacement may be critical in these patients.

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Recovery of thyroid function with a decreased titre of antimicrosomal antibody in a hypothyroid man with Hashimoto's thyroiditis

Acta Endocrinologica ◽

10.1530/acta.0.1020531 ◽

1983 ◽

Vol 102 (4) ◽

pp. 531-534 ◽

Cited By ~ 9

Author(s):

Makiko Yamamoto ◽

Kazuro Kaise ◽

Hirofumi Kitaoka ◽

Katsumi Yoshida ◽

Nobuko Kaise ◽

...

Keyword(s):

Hashimoto’S Thyroiditis ◽

Serum Levels ◽

Hashimoto's Thyroiditis ◽

Thyroid Peroxidase ◽

Normal Range ◽

Surgical Biopsy ◽

Low Levels ◽

Serum Thyroid Hormones ◽

Antimicrosomal Antibody ◽

Serum Tsh

Abstract. A 36 year old man with a diffuse goitre, signs of mild hypothyroidism, strikingly low levels of T4 (0.9 μg/dl) and T3 (24 ng/dl), elevated TSH (140 μU/ml) and elevated microsomal haemagglutination antibody (MCHA, 1:409 600), subsequently became non-goitrous and euthyroid with a decreased titre of antimicrosomal antibody without any medication. At the time of surgical biopsy, serum levels of T4 and T3 had risen to the normal range (4.6 μg/dl and 73 ng/dl, respectively), serum TSH had decreased to 30 μU/ml and the titre of MCHA to 1:25 600. Thyroid specimens showed Hashimoto's thyroiditis. The activity of thyroid peroxidase (TPO) was normal. The latest examination, 1 year and 3 months after initial evaluation, showed that the patient remained euthyroid with no goitre, that serum thyroid hormones were within the normal range (T4 7.7 μg/dl and T3 97 ng/dl), and that TSH was not detectable. The titre of MCHA decreased strikingly to 1:400.

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