Autoimmune Thyroid Disease Patients Research Articles

Evaluation of Epithelial-Mesenchymal Transition Markers in Autoimmune Thyroid Diseases.

A state of chronic inflammation is common in organs affected by autoimmune disorders, such as autoimmune thyroid diseases (AITD). Epithelial cells, such as thyroid follicular cells (TFCs), can experience a total or partial transition to a mesenchymal phenotype under these conditions. One of the major cytokines involved in this phenomenon is transforming growth factor beta (TGF-β), which, at the initial stages of autoimmune disorders, plays an immunosuppressive role. However, at chronic stages, TGF- β contributes to fibrosis and/or transition to mesenchymal phenotypes. The importance of primary cilia (PC) has grown in recent decades as they have been shown to play a key role in cell signaling and maintaining cell structure and function as mechanoreceptors. Deficiencies of PC can trigger epithelial-mesenchymal transition (EMT) and exacerbate autoimmune diseases. A set of EMT markers (E-cadherin, vimentin, α-SMA, and fibronectin) were evaluated in thyroid tissues from AITD patients and controls through RT-qPCR, immunohistochemistry (IHC), and western blot (WB). We established an in vitro TGF-β-stimulation assay in a human thyroid cell line to assess EMT and PC disruption. EMT markers were evaluated in this model using RT-qPCR and WB, and PC was evaluated with a time-course immunofluorescence assay. We found an increased expression of the mesenchymal markers α-SMA and fibronectin in TFCs in the thyroid glands of AITD patients. Furthermore, E-cadherin expression was maintained in these patients compared to the controls. The TGF-β-stimulation assay showed an increase in EMT markers, including vimentin, α-SMA, and fibronectin in thyroid cells, as well as a disruption of PC. The TFCs from the AITD patients experienced a partial transition to a mesenchymal phenotype, preserving epithelial characteristics associated with a disruption in PC, which might contribute to AITD pathogenesis.

Stress-Related Immune Response and Selenium Status in Autoimmune Thyroid Disease Patients.

Autoimmune thyroid disease (AITD), including Graves' disease (GD) or Hashimoto's thyroiditis (HT), occurs due to genetic susceptibility and environmental factors, among which the role of stressful events remains controversial. This study investigated the relationship between the number and impact of stressful life events in AITD patients with selenium status, and the Th1/Th2/Th17 immune response. The study population included three groups: HT (n = 47), GD (n = 13), and a control group (n = 49). Thyroid function parameters, autoantibody levels, and the plasma levels of cytokines, selenium, selenoprotein P (SeP), and glutathione peroxidase 3 (GPx) activity were measured. Participants filled out the Life Experiences Survey. No significant differences in the number of stressful life events were found among the patients with HT, GD, and the controls. A higher (median (interquartile range)) negative stress level (8 (4-12)) than a positive stress level (3 (1-9)) was found in the HT group. The HT group showed a correlation between SeP and the positive stress level: rs = -0.296, p = 0.048, and the GD group between GPx and the negative stress level (rs = -0.702, p = 0.011). Significant positive correlations between thyroid peroxidase antibody level and the total number of major life events (p = 0.023), the number of major life events in the last 7-12 months, and the number of major life events with no impact and a negative stress level were found. We suggest that the measurements of Th2-related cytokines and selenoproteins could be used as biomarkers for the development of AITD in cases where stress is considered a component cause of the pathogenic mechanism of the disease.

Type 3 autoimmune polyglandular syndrome (APS-3) or type 3 multiple autoimmune syndrome (MAS-3): an expanding galaxy.

The number of recognised distinct autoimmune diseases (AIDs) has progressively increased over the years with more than 100 being reported today. The natural history of AIDs is characterized by progression from latent and subclinical to clinical stages and is associated with the presence of the specific circulating autoantibodies. Once presented, AIDs are generally chronic conditions. AIDs have the tendency to cluster and co-occur in a single patient. Autoimmune thyroid diseases (AITD) are the most prevalent of AIDs in the world population, and about one-third of the AITD patients also present with a non-thyroid AID during their life-span. Furthermore, patient with non-thyroid AIDs often presents with a form of AITD as a concurrent condition. Many of the clusters of AIDs are well characterized as distinctive syndromes, while some are infrequent and only described in case reports. In this review, we describe the wide spectrum of the combinations and the intricate relationships between AITD and the other AIDs, excluding Addison's disease. These combinations are collectively termed type 3 Autoimmune Polyglandular Syndrome (APS-3), also called type 3 Multiple Autoimmune Syndrome (MAS-3), and represent the most frequent APS in the world populations. Numerous associations of AITD with various AIDs could be viewed as if the other AIDs were gravitating like satellites around AITD located in the center of a progressively expanding galaxy of autoimmunity.

Intraindividual variation in histone acetylation and its impact on autoimmune thyroid diseases.

Autoimmune thyroid diseases (AITDs), such as Graves' disease (GD) and Hashimoto's disease (HD), are organ-specific autoimmune diseases. Histone acetylation, especially that of histone H3, is an epigenetic mechanism that regulates gene expression and is associated with the development of autoimmune diseases. However, physiological variations in histone acetylation are not yet clear, and we believe that physiological variations should be examined prior to analysis of the role of histone H3 in the pathogenesis of AITDs. In this study, we analyzed histone H3 acetylation levels in peripheral blood mononuclear cells (PBMCs) using a histone H3 total acetylation detection fast kit. Blood samples were collected before meals, between 8:30-9:00 am, daily for 10 weeks to evaluate the daily variation. At 4 days, blood was also collected before meals three times a day (at 8:30-9:00, 12:30-13:00, and 16:30-17:00) to evaluate circadian variation. Then, histone H3 acetylation levels were evaluated in AITD patients to clarify the association with the pathogenesis of AITD. Although we could not find a common pattern of circadian variance, we observed daily variation in histone H3 acetylation levels, and their coefficient of variances (CVs) were approximately 48.3%. Then, we found that histone H3 acetylation levels were significantly lower in GD and HD patients than in control subjects and these differences were larger than the daily variation in histone acetylation. In conclusion, histone H3 acetylation levels were associated with the development of AITD, even allowing for daily variation.

Platelet abnormalities in autoimmune thyroid diseases: A systematic review and meta-analysis.

Some degree of platelet index abnormality has been found clinically in the autoimmune thyroid disease (AITD), but the findings are not uniform. The PubMed, Web of Science, Cochrane Library, and Embase databases were searched for relevant articles published up to August 16th, 2022, with no restrictions on the language of the articles. Reference lists of eligible articles were also searched. A random effect model was used to pool the standardized mean difference (SMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), and platelet distribution width (PDW) between AITD patients and healthy controls, and subgroup analyses were performed. A total of 19 articles with 6173 people (3824 AITD patients and 2349 healthy people) were included in the meta-analysis. The results showed that PLT and MPV values were significantly increased in AITD patients when compared with healthy people (SMD: 0.164, 95% CI: 0.044 to 0.285; SMD: 0.256, 95% CI: 0.013 to 0.500), while no significant difference was found in PDW between the AITD group and the control group (SMD: 0.060, 95% CI: -0.164 to 0.284). Subgroup analysis according to disease type and thyroid function revealed that for PLT, this difference was only found in the Hashimoto's thyroiditis (HT) and hypothyroid groups, but not in the Graves' disease (GD) and hyperthyroid groups. For MPV, the results were the opposite of those for PLT: MPV was significantly higher in the GD, hyperthyroid, and euthyroid groups than in the control group, but not in the HT and hypothyroid groups. Sensitivity analysis showed that the stability of the pooled MPV was not good. No publication bias was found. PLT and MPV are significantly elevated in patients with AITD, with PLT being more significantly elevated in HT and hypothyroidism, and MPV being more significantly increased in GD and hyperthyroidism. Appropriate clinical attention can be paid to the thyroid function of patients when abnormal platelet indices are found, and conversely, the consequences of abnormal platelet parameters such as elevated MPV lead to an increased occurrence of cardiovascular events, which should also be addressed in the AITD population. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022341823.

Helper T Cell 17 and Regulatory T Cell Levels in Peripheral Blood of Newly Diagnosed Patients with Autoimmune Thyroid Disease: A Meta-Analysis.

This article aims to explore associated immune indicators of autoimmune thyroid disease (AITD) through a meta-analysis of published case-control studies on newly diagnosed AITD patients, intending to provide some suggestions for research on the mechanisms of AITD. Six electronic databases were searched for case-control studies on newly diagnosed AITD patients from inception to August 15, 2022. A random-effects model was used to calculate the standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (95% CI). A total of 26 articles were included in this meta-analysis. Patients with newly diagnosed AITD had higher levels of helper T cell 17 (Th17) (Hashimoto's disease (HT): SMD=2.35, 95% CI: 1.98, 2.72; Graves' disease (GD): SMD=1.61, 95% CI: 1.23, 1.98), lower levels of regulatory T cell (Treg) (HT: SMD=-2.04, 95% CI: -2.67, -1.42; GD: SMD=-1.35, 95% CI: -2.11, -0.58), and lower levels of forkhead box P3 (FoxP3) mRNA (HT: SMD=-2.58, 95% CI: -3.12, -2.05; GD: SMD=-2.13, 95% CI: -2.56, -1.70), compared to the healthy population. In addition, the single nucleotide polymorphism rs3761548 and rs3761549 in the promoter region of FoxP3 showed a higher frequency in the comparison of genotype "CT" only in HT patients than in the healthy population (OR=1.66, 95%CI: 1.18, 2.34). In patients with newly diagnosed AITD, the Th17/Treg ratio imbalance may develop AITD. Monitoring Th17 and Treg levels may become an essential tool to assess the organism's immune homeostasis and hopefully guide clinical diagnosis and treatment.

Use of thyroid stimulating hormone receptor antibodies test in an outpatient endocrinology clinic fordifferential diagnosis ofhyperthyroidism

Objective. Antibodies (Abs) to the thyroid stimulating hormone receptor (TSHR) play an important role in the pathogenesis of autoimmune thyroid disease (AITD). We define the complex terminology that has arisen to describe TSHR-Abs, and discuss significant advances that have been made in the development of clinically useful TSHR-Abs assays. Methods. Literature review and discussion. Results. TSHR-Abs may mimic or block the action of TSH or be functionally neutral. Stimulating TSHR-Abs are specific biomarkers for Graves’ disease and responsible for many of its clinical manifestations. TSHR-Abs may also be found in patients with Hashimoto thyroiditis in whom they may contribute to the hypothyroidism. Measurement of TSHR-Abs in general, and functional Abs in particular is recommended for the rapid diagnosis of Graves’ disease, differential diagnosis and management of patients with AITD, especially during pregnancy, and in AITD patients with extrathyroidal manifestations such as orbitopathy. Measurement of TSHR-Abs can be done with either immunoassays that detect specific binding of Abs to the TSHR or cell-based bioassays, which also provide information on their functional activity and potency. Application of molecular cloning techniques has led to significant advances in methodology that have enabled the development of clinically useful bioassays. When ordering TSHR-Abs, clinicians should be aware of the different tests available and how to interpret results based on which assay is performed. The availability of an international standard and continued improvement in bioassays will help promote their routine performance by clinical laboratories and provide the most clinically useful TSHR-Abs results. Conclusion. Measurement of TSHR-Abs in general, and functional (especially stimulating) Abs in particular is recommended for the rapid diagnosis, differential diagnosis, and management of patients with Graves hyperthyroidism, related thyroid eye disease, during pregnancy, as well as in Hashimoto thyroiditis patients with extrathyroidal manifestations and/or thyroid-binding inhibiting immunoglobulin positivity.

Antiphospholipid antibodies in autoimmune thyroid diseases.

Antiphospholipid (aPL) antibodies have been reported in several autoimmune diseases. The aim of this study was to evaluate the frequency of aPL (anti-cardiolipin antibodies (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI)) in patients with autoimmune thyroid diseases (AITD). One hundred and ninety-five patients with AITD (139 Hashimoto's thyroiditis (HT) patients and 56 Graves' disease (GD) patients) and 90 healthy blood donors (HBD) were studied. IgG, IgA and IgM aCL and aβ2GPI were determined by ELISA. One hundred fifty-four AITD patients were women and 41 were men. Fifty-six healthy subjects were women and 34 were men. The median age of patients and the control group was 45 and 38.5 years, respectively. The frequency of aPL was significantly higher in patients with AITD and in patients with HT than in HBD (33.3% vs 11.1%, p < 10-3 and 38.1% vs 11.1%, p < 10-3 ). The frequency of aPL in GD was significantly lower than in HT (21.4% vs 38.1%, p=0.025). In patients with HT, aβ2GPI (34.5%) was significantly more frequent than aCL (13.6%) (p < 10-3 ). The frequency of aβ2GPI was significantly higher in patients with HT than in healthy population (34.5% vs 11.1%, p < 10-3 ). In HT patients, IgA isotype of aβ2GPI was significantly more common than in HBD and in GD patients (27.3% vs 7.8%, p < 10-3 and 27.3% vs 12.5%, p=0.02, respectively). aβ2GPI and not aCL were frequent in AITD. IgA was the predominant isotype of aβ2GPI. aβ2GPI-IgA was more frequent in HT than in GD.

MBL2 polymorphism may be a protective factor of autoimmune thyroid disease susceptibility.

Genetic susceptibility is an essential pathogenetic mechanism in autoimmune thyroid disease (AITD). MBL2 gene polymorphisms have been shown to play a vital role in the pathogenesis of multiple autoimmune disorders, but its contribution to AITD is unclear. The aim of this study was to assess the linkage between MBL2 gene polymorphisms and AITD susceptibility in a Chinese Han population. One thousand seven hundred sixty seven subjects consisting of 965 AITD patients and 802 controls from a Chinese Han population were enrolled in the case-control study. Four common single-nucleotide polymorphisms (SNPs) in the MBL2 gene were tested using high-throughput sequencing technology for sequence-based SNP genotyping. The allele and genotype distribution results showed that the minor alleles of rs198266, rs10824793, and rs4935046 were significantly lower in Hashimoto's thyroiditis (HT) patients than in healthy controls. In further genetic model analysis, the dominant models of rs1982266, rs10824793, and rs4935046 for MBL2 in the AITD group exhibited a lower risk of morbidity. Finally, we discovered that haplotype AAGC was associated with Graves' disease (GD), while AGC was associated with HT. Our study provides strong evidence for a genetic correlation between MBL2 and AITD, and the polymorphism of the MBL2 gene may be a protective factor for AITD, especially for HT. These findings can advance our understanding of the etiology of AITD, as well as provide guidance for prevention and intervention toward AITD.

High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1.

Autoimmune thyroid disease (AITD), the most common autoimmune disease, includes Graves' disease (GD) and Hashimoto's thyroiditis (HT). Currently, the pathogenesis of AITD is not fully understood. Our study aimed to examine the presence of macrophage polarization imbalance in AITD patients, to investigate whether high iodine can cause macrophage polarization imbalance, and to investigate the role of key genes of metabolic reprogramming in macrophage polarization imbalance caused by high iodine. We synergistically used various research strategies such as systems biology, clinical studies, cell culture and mouse disease models. Gene set enrichment analysis (GSEA) revealed that M1 macrophage hyperpolarization was involved in the pathogenesis of AITD. In vitro and in vivo experiments showed that high iodine can affect the polarization of M1 or M2 macrophages and their related cytokines. Robust rank aggregation (RRA) method revealed that hexokinase 3 (HK3) was the most aberrantly expressed metabolic gene in autoimmune diseases. In vitro and in vivo studies revealed HK3 could mediate macrophage polarization induced by high iodine. In summary, hyperpolarization of M1-type macrophages is closely related to the pathogenesis of AITD. High iodine can increase HK3 expression in macrophages and promote macrophage polarization towards M1. Targeting HK3 can inhibit M1 polarization induced by high iodine.

Serum IgG4 level for malignancy prediction in indeterminate thyroid nodules among patients with or without autoimmune thyroid disease

The incidence of thyroid nodules (TNs) has increased nowadays, and it is critical to properly differentiate between malignant and benign nodules to prevent unneeded thyroidectomy as well as complications related to surgery. IgG4 significantly contributes to various cancer-associated processes. The present study aimed to assess the value of serum IgG4 level in predicting malignancies in indeterminate thyroid nodules (ITN) among patients with and without autoimmune thyroid disease (AITD). A total of 67 patients with indeterminate cytology thyroid nodules (Bethesda III and IV, according to Bethesda system for reporting thyroid cytopathology) were selected. Preoperative serum thyroid profile, IgG4, anti-thyroglobulin (TG) and anti-thyroid peroxidase (TPO) antibody levels were determined. After total thyroidectomy, patients were categorized based on the postoperative histopathology outcome into two groups. Group (I): confirmed benign nodules (n=55) and Group (II): confirmed malignant TNs (n=12). IgG4 levels were significantly elevated among malignant TNs patients than in benign TNs patients, with a median (IQR) of 194.5 mg/dl (183 - 214) vs. 91 mg/dl (60 - 113), respectively (P=0.001). The cut-off value for differentiation between malignant and benign TNs was >180 mg/dl with a sensitivity of 75% and specificity of 100%. There was a significant positive correlation between thyroid antibodies and IgG4 levels (P=0.001). AITD patients had significantly higher level of IgG4 compared with those without AITD 189 mg/dl (153 - 208) vs 89 mg/dl (58 - 112), respectively (P =0.001). Eighty percent (12/15) of patients with AITD had malignant TNs with IgG4 >180 mg/dl, while 20% (3/15) of patients with benign TNs showed IgG4 levels < 180 mg/dl. In conclusion, IgG4 level can be proposed as a predictor of malignant TNs.

HLA-DRA Gene Polymorphisms Are Associated with Graves' Disease as an Autoimmune Thyroid Disease.

Background Autoimmune thyroid disease (AITD), one of the most prevalent organ-specific autoimmune diseases, mainly includes Graves' disease (GD) and Hashimoto's thyroiditis (HT). This study was aimed at researching the association between AITD and single nucleotide polymorphisms (SNPs) of the HLA-DRA gene. Methods Using Hi-SNP high-throughput sequencing technology, we detected the distribution of three SNPs (rs3177928, rs7197, and rs3129878) of HLA-DRA genotypes in 1033 AITD patients (634 GD and 399 HT ones) and 791 healthy volunteers in Chinese Han Population. Chi-square test, multivariate logistic regression, and haplotype analysis were performed by SPSS and Haploview software to analyze the relationship between HLA-DRA gene polymorphisms and AITD. Results The results show that allele frequency and genotype distribution of rs3177928 and rs7197 were correlated with AITD and GD compared with the healthy control group, but not with HT. Rs3177928 and rs7197 were correlated with AITD and HT in the allele model, dominant model, and overdominant model before and after gender and age adjustment, but not with HT. In addition, we found that two loci (rs3177928 and rs7197) constituted a linkage disequilibrium (LD) region, and haplotype AA was associated with AITD and GD. However, we found no association between rs3129878 and AITD. Conclusion Our study is the first to find that rs3177928 and rs7197 of HLA-DRA are significantly correlated with AITD and GD in the Chinese Han population. This will help further reveal the pathogenesis of AITD and provide new candidate genes for the prediction or treatment of AITD.

Children and adolescent patients with goiter and normal thyroid function: US findings related to underlying autoimmune thyroid diseases.

This study was conducted to investigate and compare thyroid ultrasonography (US) findings in children and adolescents with goiter and normal thyroid function with positive or negative thyroid autoimmunity. From 2000 to 2020, we reviewed initial thyroid US images in 33 autoimmune thyroid diseases (AITDs) patients and 52 nonAITD patients. Our review of the images focused on thyroid parenchymal hypoechogenicity and heterogeneous echopattern subdivided into 2 groups according to severity: hypoechogenicity 1 and 2 (HO1 and HO2) and heterogeneity 1 and 2 (HE1 and HE2). HO1 and HE1 were observed more frequently in the nonAITD group (86.5% and 42.3%, respectively), while HO2 and HE2 were observed more frequently in the AITDs group (36.4% and 81.8%, respectively). More patients in the AITDs group showed change of both US groups and thyroid function state within the follow-up periods than in nonAITD group (33.3% and 5.77%, respectively). Children and adolescent AITDs patients showed more severe parenchyma hypoechogenicity and heterogeneous echopattern compared with nonAITD patients with goiter and normal thyroid function.

Patients with Autoimmune Thyroid Diseases Have Higher Prevalence of Positive Antiphospholipid Antibodies: A Systematic Review and Meta-Analysis.

Introduction Autoimmune thyroid diseases (AITDs) and antiphospholipid syndrome (APS) are commonly seen in childbearing-age women and can lead to recurrent miscarriages. Studies with a relatively small sample size were conducted and concluded inconsistent results on the relationship between AITDs and APS or the presence of antiphospholipid (aPL) antibodies. This meta-analysis aimed to provide evidence on the possible association between AITDs and APL using primary data from all relevant studies. Methods Literature databases including PubMed, Embase, and Cochrane were searched from the time when the databases were established to March 2022. A total of 7 studies that met all inclusion criteria were selected in this meta-analysis, with 475 AITD patients and 764 healthy controls. After data extraction, the pooled odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. Results The risk of positive APL in AITD patients was approximately 3 folds higher in AITD patients compared with those in healthy controls (OR 3.41, 95% CI 2.29–5.08, p < 0.001). There was no significant association between the risk of Graves' disease (GD) and positive APL (OR 9.3, 95% CI 0.10–824.73, p=0.33). The risk of positive APL in patients with Hashimoto's thyroiditis (HT) increased over 2 folds compared with healthy controls (OR 3.35, 95% CI 1.55–7.23, p=0.002). Conclusions The result of this meta-analysis proved that the presence of APL was significantly increased in patients with AITD compared with healthy individuals, especially in patients with Hashimoto's thyroiditis.

LINC01061 triggers inflammation and inflammasome activation in autoimmune thyroiditis via microRNA-612/BRD4 axis

Considering the significance of LINC01061 in papillary thyroid cancer, here, we commenced to study the role of LINC01061 in autoimmune thyroid disease (AITD) and the potential mechanism. Thyroid tissues were attained from patients with AITD, and Nthy-ori 3–1 cells were induced with lipopolysaccharide (LPS), followed by measurement of LINC01061, microRNA (miR)-612, and BRD4 expression as well as their binding relation. The ectopic expression and silencing experimentations were carried out in LPS-induced Nthy-ori 3–1 cells to detect cell viability and apoptosis as well as inflammation and inflammasome. BRD4 and LINC01061 upregulation and miR-612 downregulation were observed in thyroid tissues of AITD patients and LPS-induced Nthy-ori 3–1 cells. Mechanistic analysis manifested that LINC01061 bound to miR-612 that negatively targeted BRD4. LINC01061 upregulated BRD4 to enhance cell viability, trigger inflammation and inflammasome activation but reduce apoptosis of LPS-induced Nthy-ori 3–1 cells by sponging miR-612. In conclusion, LINC01061 induced the occurrence of AITD by upregulation of miR-612-mediated BRD4 expression.

Association of ANKRD55 Gene Polymorphism with HT: A Protective Factor for Disease Susceptibility.

Purpose Recent studies have shown that Ankyrin Repeat Domain 55 (ANKRD55) gene polymorphism is a risk factor for multiple autoimmune diseases, but its association with autoimmune thyroid diseases (AITDs) has not been reported. The purpose of this study was to investigate the potential relationship between polymorphism of the ANKRD55 gene and AITDs. Methods For this study, we enrolled 2050 subjects, consisting of 1220 patients with AITD and 830 healthy subjects. Five loci (rs321776, rs191205, rs7731626, rs415407, and rs159572) of the ANKRD55 gene were genotyped using Multiplex PCR combined with high-throughput sequencing. Results The results showed that the allele frequencies of rs7731626 and rs159572 loci in HT patients were lower than those in normal controls (P=0.048 and P=0.03, respectively). In different genetic model analyses, rs7731626 and rs159572 were also significantly correlated with HT in allele, dominant and additive models before and after age and sex adjustment. There were no differences in rs321776, rs191205, or rs415407 of the ANKRD55 gene in allele frequency or genotype frequency between AITDs patients and controls. Conclusions This study for the first time found that rs7731626 and rs159572 of ANKRD55 were significantly correlated with HT, and individuals carrying the A allele at these two loci had a lower probability of developing HT.

High Prevalence of Common Human Viruses in Thyroid Tissue.

IntroductionEvidence points to viral infections as possible triggers of autoimmune thyroid disease (AITD), but little is known about the prevalence of common viruses in the thyroid gland. Using a novel approach based on virus enrichment in multiple cell lines followed by detection of the viral genome and visualization of viral proteins, we investigated the presence of multiple human viruses in thyroid tissue from AITD patients and controls.MethodsThyroid tissue was collected by core needle biopsy or during thyroid surgery from 35 patients with AITD (20 Graves’ disease and 15 Hashimoto’s thyroiditis). Eighteen thyroid tissue specimens from patients undergoing neck surgery for reasons other than thyroid autoimmunity served as controls. Specimens were tested for the presence of ten different viruses. Enteroviruses and human herpesvirus 6 were enriched in cell culture before detection by PCR and immunofluorescence, while the remaining viruses were detected by PCR of biopsied tissue.ResultsForty of 53 cases (75%) carried an infectious virus. Notably, 43% of all cases had a single virus, whereas 32% were coinfected by two or more virus types. An enterovirus was found in 27/53 cases (51%), human herpesvirus 6 in 16/53 cases (30%) and parvovirus B19 in 12/53 cases (22%). Epstein-Barr virus and cytomegalovirus were found in a few cases only. Of five gastroenteric virus groups examined, only one was detected in a single specimen. Virus distribution was not statistically different between AITD cases and controls.ConclusionCommon human viruses are highly prevalent in the thyroid gland. This is the first study in which multiple viral agents have been explored in thyroid. It remains to be established whether the detected viruses represent causal agents, possible cofactors or simple bystanders.

The Relationship between VEGFC Gene Polymorphisms and Autoimmune Thyroiditis.

Background Autoimmune thyroid diseases (AITDs), representative autoimmune diseases, mainly consist of Graves' disease (GD) and Hashimoto's thyroiditis (HT). In this passage, we investigated the association between vascular endothelial growth factor C (VEGFC) gene polymorphisms and AITDs. Methods A total of 1084 patients with AITDs and 794 healthy controls were tested for VEGFC gene genotypes in four single nucleotide polymorphisms (SNPs) by high-throughput sequencing, and the correlation between VEGFC gene polymorphisms and AITDs was statistically analyzed. Results The genotype distribution of rs3775194 was statistically associated with AITDs compared with the control group. Rs3775194 was associated with AITDs under the overdominant model, both before and after adjusting for confounding factors, while the other three SNPs were not associated with GD and HT. There was a prominent discrepancy between male healthy controls and male AITD patients under overdominant model in rs3775194 and the recessive model in rs11947611. The genotype distribution of rs3775194 was statistically related to male HT. Conclusion These results reveal the correlation between VEGFC mutation and AITD susceptibility.

Celiac Disease and Autoimmune Thyroid Disease: The Two Peas in a Pod.

Celiac disease (CD) is a small intestinal inflammatory disease commonly seen in the Western population. It has been observed that patients with monoglandular and polyglandular autoimmunity have a higher prevalence of celiac disease. Hashimoto's thyroiditis (HT) and Graves' disease (GD), which mainly constitute the autoimmune thyroid diseases (AITD), characterized by lymphocytic infiltration of the thyroid parenchyma, are noted to be frequently associated with celiac disease. The fundamental mechanism of this frequent coexistence is thought to be a shared genetic background. Due to the subclinical nature of the celiac disease, the diagnosis is often missed or made coincidentally during screening. The rising prevalence of the celiac disease among AITD patients has urged researchers to investigate the link between the two. We reviewed the most recent and relevant literature on the intriguing relationship between celiac disease and thyroid autoimmunity. The objectives of this article were to study the shared genetic background, the incidence of CD in AITD, the effect of a gluten-free diet on AITD, and the need for routine screening of CD in AITD patients.

Association Between Polymorphisms of IL-23/IL-17 Pathway and Clinical Phenotypes of Autoimmune Thyroid Diseases.

Several autoimmune and inflammatory disorders, including autoimmune thyroid diseases (AITD), have been linked to Th17 cells and the IL-23/IL-17 axis. Current data suggest that genetic variation contributes greatly to disease susceptibility to AITD. To study the role of single nucleotide polymorphisms (SNPs) of IL-23/IL-17 pathway in AITD predisposition and test the gene-gene/gene-sex interactions in these loci. A total of 1051 patients with AITD, including 657 patients with Graves' disease (GD) and 394 patients with Hashimoto's thyroiditis (HT), and 874 healthy controls were enrolled in this case-control association study. Six SNPs were selected and genotyped by multiplex PCR combined with high-throughput sequencing. Interactions were tested by the general multifactor dimensionality reduction (GMDR) method. Allele C and combinational genotype AC+CC of rs3212227 within IL-23 were significantly associated with GD with goiter (p=0.003 and 0.014, respectively). Allele G and combinational genotype AG+GG of rs4819554 within IL-17RA were significantly related to HT with family history and the severity of HT (p=0.011 and 0.027; p=0.041 and 0.035). Also, allele T and genotype CT+TT of rs9463772 within IL-17F were significantly correlated with the severity of HT (p=0.001 and 0.027, respectively). Moreover, high dimensional gene-sex interaction (IL-23R-IL-23-IL-17RA-IL-17F-sex) was identified in AITD, GD, and HT patients with GMDR analysis. Our study identified the novel loci and gene-sex interaction in AITD. This evidence, from another perspective, suggests that sex, IL-23/IL-17 pathway, and Th17 cells play an important role in the pathogenesis of AITD.