scholarly journals Susceptibility Genes in Thyroid Autoimmunity

2005 ◽  
Vol 12 (1) ◽  
pp. 47-58 ◽  
Author(s):  
Yoshiyuki Ban ◽  
Yaron Tomer
Keyword(s):  
Genetic Susceptibility ◽  
Thyroid Autoimmunity ◽  
Twin Studies ◽  
Epidemiological Data ◽  
Susceptibility Genes ◽  
Autoimmune Response ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Genome Screening ◽  
Shared Genetic

The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely, these loci interact and their interactions may influence disease phenotype and severity.

scholarly journals Genetic Factors of Autoimmune Thyroid Diseases in Japanese

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Yoshiyuki Ban
Keyword(s):  
Genetic Susceptibility ◽  
Twin Studies ◽  
Epidemiological Data ◽  
Susceptibility Genes ◽  
Thyroid Diseases ◽  
Autoimmune Response ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Genome Screening ◽  
Shared Genetic

Autoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are caused by immune response to self-thyroid antigens and affect approximately 2–5% of the general population. Genetic susceptibility in combination with external factors, such as smoking, viral/bacterial infection, and chemicals, is believed to initiate the autoimmune response against thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITDs. Various techniques have been employed to identify genes contributing to the etiology of AITDs, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked to AITDs, and, in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to GD and HT and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. Known AITD-susceptibility genes are classified into three groups: HLA genes, non-HLA immune-regulatory genes (e.g., CTLA-4, PTPN22, and CD40), and thyroid-specific genes (e.g., TSHR and Tg). In this paper, we will summarize the latest findings on AITD susceptibility genes in Japanese.

scholarly journals Searching for the Autoimmune Thyroid Disease Susceptibility Genes: From Gene Mapping to Gene Function

2003 ◽  
Vol 24 (5) ◽  
pp. 694-717 ◽  
Author(s):  
Yaron Tomer ◽  
Terry F. Davies
Keyword(s):  
Genetic Susceptibility ◽  
Cytotoxic T Lymphocyte ◽  
Twin Studies ◽  
Human Leukocyte ◽  
Epidemiological Data ◽  
Susceptibility Genes ◽  
Autoimmune Response ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Genome Screening

Abstract The autoimmune thyroid diseases (AITD) are complex diseases that are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility, in combination with external factors (e.g., dietary iodine), is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been used to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g., human leukocyte antigen, cytotoxic T lymphocyte antigen-4) and thyroid-specific genes (e.g., TSH receptor, thyroglobulin). Most likely these loci interact, and their interactions may influence disease phenotype and severity. It is hoped that in the near future additional AITD susceptibility genes will be identified and the mechanisms by which they induce AITD will be unraveled.

Identification Of New Rare Variants Associated With Familial Autoimmune Thyroid Diseases By Deep Sequencing Of Linked Loci

2021 ◽  
Author(s):  
Cheuk Wun Li ◽  
Ravi Sachidanandam ◽  
Anitha Jayaprakash ◽  
Zhengzi Yi ◽  
Weijia Zhang ◽  
...  
Keyword(s):  
Genetic Susceptibility ◽  
Deep Sequencing ◽  
Rare Variants ◽  
Thyroid Autoimmunity ◽  
Susceptibility Genes ◽  
Thyroid Diseases ◽  
Phosphoglycerate Mutase ◽  
Inositol Polyphosphate ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

Abstract Context Genetic risk factors play a major role in the pathoetiology of autoimmune thyroid diseases (AITD). So far, only common risk variants have been identified in AITD susceptibility genes. Recently, rare genetic variants have emerged as important contributors to complex diseases, and we hypothesized that rare variants play a key role in the genetic susceptibility to AITD. Objective To identify new rare variants that are associated with familial AITD. Design We performed deep sequencing of 3 previously mapped AITD-linked loci (10q, 12q, and 14q) in a dataset of 34 families in which AITD clustered (familial AITD). Results We identified 13 rare variants, located in the inositol polyphosphate multikinase (IPMK) gene, that were associated with AITD (i.e. both Graves’ disease [GD] and Hashimoto’s thyroiditis [HT]); two rare variants, within the dihydrolipoamide S-succinyltransferase (DLST) and zinc-finger FYVE domain-containing protein (ZFYVE1) genes, that were associated with GD only; and 3 rare variants, within the phosphoglycerate mutase 1 pseudogene 5 (PGAM1P5), LOC105369879, and methionine aminopeptidase 2 (MetAP2) genes, that were associated with HT only. Conclusion Our study demonstrates that, in addition to common variants, rare variants also contribute to the genetic susceptibility to AITD. We identified new rare variants in 6 AITD susceptibility genes that predispose to familial AITD. Of them three genes, IPMK, ZFYVE1, and MetAP2, are mechanistically involved in immune pathways and have been previously shown to be associated with autoimmunity. These genes predispose to thyroid autoimmunity and may in the future serve as potential therapeutic targets.

scholarly journals Immunological Mechanisms of Autoimmune Thyroid Diseases: A Shift in The Traditional TH1/TH2 Paradigm

2019 ◽  
Vol 73 (2) ◽  
pp. 67-77
Author(s):  
Tatjana Zaķe ◽  
Sandra Skuja ◽  
Aivars Lejnieks ◽  
Valērija Groma ◽  
Ilze Konrāde
Keyword(s):  
Thyroid Autoimmunity ◽  
Treg Cells ◽  
Thyroid Diseases ◽  
Autoimmune Response ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Th17 Lymphocytes ◽  
Immunological Mechanisms ◽  
Thyroid Autoantigens ◽  
The Impact

Abstract Autoimmune thyroid diseases (AITD) mainly include Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), which are characterised by the presence of circulating antibodies against various thyroid autoantigens and infiltration of the thyroid gland by autoreactive lymphocytes. Despite the significant advancement in the knowledge of AITD pathogenesis in the last decade, the specific immunological mechanisms responsible for development of the disease are not thoroughly understood. Classically, HT has long been considered as a T helper (Th)1-mediated disease, while a Th2-driven autoimmune response is dominant for GD development. However, this classification has changed due to the description of Th17 lymphocytes, which suggested participation of these cells in AITD, particularly HT pathogenesis. Moreover, a shift in the balance between Th17 and T regulatory (Treg) cells has been observed in thyroid autoimmunity. We have observed overexpression of IL-17, the prominent effector cytokine of Th17, within thyroid tissues from HT and GD patients in our studies. The present review will focus on recent data regarding the role of Treg and Th17 lymphocytes in AITD pathogenesis. In addition, the impact and proposed mechanisms of the predominant environmental factors triggering the autoimmune response to the thyroid will be discussed.

The Detection of Serum IgMs to Thyroglobulin in Subacute Thyroiditis Suggests a Protective Role of IgMs in Thyroid Autoimmunity

2020 ◽  
Vol 105 (6) ◽  
pp. e2261-e2270 ◽  
Author(s):  
Debora Ricci ◽  
Alessandro Brancatella ◽  
Michele Marinò ◽  
Mario Rotondi ◽  
Luca Chiovato ◽  
...  
Keyword(s):  
De Novo ◽  
Thyroid Autoimmunity ◽  
High Serum ◽  
Subacute Thyroiditis ◽  
Autoimmune Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

Abstract Context The role of serum immunoglobulin (Ig)Ms in autoimmune thyroid diseases is uncertain. Objective We looked for IgMs to thyroglobulin (Tg) in patients with subacute thyroiditis (SAT), which is characterized by high serum Tg levels, the possible de novo appearance of IgGs to Tg (TgAb-IgGs), and no autoimmune sequelae. Main Outcome Measures TgAb-IgMs and TgAb-IgGs were detected by binding to Tg using the enzyme-linked immunosorbent assay (ELISA). The upper reference limit of TgAb-IgMs and TgAb-IgGs was established in 40 normal subjects. We looked for TgAb-IgMs in 16 patients with SAT, 11 with Hashimoto’s thyroiditis (HT), and 8 with Graves’ disease (GD) who were all positive for TgAb-IgGs. IgM binding to bovine serum albumin (BSA), keyhole limpet hemocyanin (KLH), and glucagon in ELISA was measured. Inhibition of TgAb-IgMs binding to coated Tg was evaluated by preincubating serum samples or IgG-depleted samples with soluble Tg. Results TgAb-IgMs were positive in 10/16 patients with SAT, 2/11 with HT, and 1/8 with GD. TgAb-IgMs were higher in SAT (0.95; 0.42–1.13) (median; 25th–75th percentiles) than in HT (0.47; 0.45–0.51) and GD patients (0.35; 0.33–0.40) (P < .005 for both). IgM binding of SAT sera to BSA, KLH, and glucagon was significantly lower than Tg. Preincubation with soluble Tg reduced the binding of IgMs to coated Tg by 18.2% for serum samples and by 35.0% and 42.1% for 2 IgG-depleted samples. TgAb-IgM levels were inversely, although nonsignificantly, correlated with Tg concentrations. Conclusions Tg leak associated with thyroid injury induces the production of specific TgAb-IgMs, which, in turn, increases the clearance of Tg and might prevent the establishment of a persistent thyroid autoimmune response.

Genetic Study in a Large Cohort Supported Different Pathogenesis of Graves’ Disease and Hashimoto’s Hypothyroidism

2020 ◽  
Vol 105 (7) ◽  
pp. e2600-e2608 ◽  
Author(s):  
Qian-Yue Zhang ◽  
Wei Liu ◽  
Lu Li ◽  
Wen-Hua Du ◽  
Chun-Lin Zuo ◽  
...  
Keyword(s):  
Susceptibility Genes ◽  
Graves Disease ◽  
Susceptibility Loci ◽  
Chinese Han ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Genome Wide ◽  
Chinese Cohort ◽  
First Time ◽  
Genome Wide Significance

Abstract Context Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are the 2 main autoimmune thyroid diseases that have both similarities and differences. Determining the genetic basis that distinguishes HT from GD is key for a better understanding of the differences between these closely related diseases. Objects To identify the susceptibility genes for HT in the Chinese cohort and compare susceptibility genes between GD and HT. Design In the current study, 18 SNPs from 18 established GD risk loci were selected and then genotyped in 2682 patients with HT, 4980 patients with GD, and 3892 controls. The association analysis between HT and controls and heterogeneity analysis between HT and GD were performed on SPSS, with the logistic regression analysis adjusted for sex and age. Results We identified 11 susceptibility loci for HT in the Chinese Han population, with 4 loci, including the rs1265883 in SLAMF6 locus, rs1024161 in CTLA4, rs1521 in HLA-B, and rs5912838 in GPR174/ ITM2A at X chromosome, reaching genome-wide significance of 5 × 10–8. Five loci were reported to be associated with HT for the first time. We also identified 6 susceptibility loci with heterogeneity between GD and HT. Out of them, 4 loci were associated with GD but not with HT, including HLA-DPB1, CD40, TSHR, and TG; the association of HLA-B with GD was stronger than that with HT, but the association of SLAMF6 was reversed. Conclusion Our findings suggested that the pathogenesis of HT and GD was different.

scholarly journals High Prevalence of Antinuclear Antibodies in Children with Thyroid Autoimmunity

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Maria Segni ◽  
Ida Pucarelli ◽  
Simona Truglia ◽  
Ilaria Turriziani ◽  
Chiara Serafinelli ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Rheumatic Diseases ◽  
Antinuclear Antibodies ◽  
Pediatric Patients ◽  
Thyroid Autoimmunity ◽  
Disease Onset ◽  
Nuclear Antigen ◽  
Chronic Lymphocytic Thyroiditis ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

Background. Antinuclear antibodies (ANA) are a hallmark of many autoimmune diseases and can be detected many years before disease onset. Autoimmune thyroid diseases (AITD) are frequently associated with other organ- and non-organ-specific autoimmune disorders.Objectives. To assess the prevalence of ANA in pediatric patients with AITD and their clinical correlations.Methods. Ninety-three consecutive pediatric patients with AITD were enrolled (86 children with chronic lymphocytic thyroiditis and 7 with Graves’ disease). ANA, anti-double DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen (anti-ENA), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) was obtained. Signs and symptoms potentially related to rheumatic diseases in children were investigated by a questionnaire.Results. ANA positivity was found in 66/93 children (71%), anti-ENA in 4/93 (4.3%), anti-dsDNA in 1/93 (1.1%), RF in 3/93 (3.2%), and anti-CCP in none. No significant differences were found between the ANA-positive and ANA-negative groups with respect to age, sex, L-thyroxine treatment, or prevalence of other autoimmune diseases. Overall, parental autoimmunity was found in 23%.Conclusions. ANA positivity was demonstrated in 71% of children with AITD. ANA positivity was not related to overt immune-rheumatic diseases. However, because the positivity of ANA can occur even many years before the onset of systemic autoimmune diseases, prospective studies are warranted.

scholarly journals The Role of Eating Behaviours in Genetic Susceptibility to Obesity

2020 ◽  
Vol 9 (4) ◽  
pp. 512-521
Author(s):  
Moritz Herle ◽  
Andrea D. Smith ◽  
Alice Kininmonth ◽  
Clare Llewellyn
Keyword(s):  
Genetic Susceptibility ◽  
Genetic Risk ◽  
Genetic Research ◽  
Twin Studies ◽  
Eating Behaviours ◽  
Genetic Liability ◽  
The Past ◽  
Uncontrolled Eating ◽  
Shared Genetic

Abstract Purpose of Review Eating behaviours are hypothesised to be the behavioural expression of genetic risk of obesity. In this review, we summarise findings from behavioural genetic research on the association between genetic risk for obesity and validated psychometrics measures of eating behaviours in children and adults (published in the past 10 years). Recent Findings Twin studies have produced some evidence for a shared genetic aetiology underlying body mass index and eating behaviours. Studies using measured genetic susceptibility to obesity have suggested that increased genetic liability for obesity is associated with variation in obesogenic eating behaviours such as emotional and uncontrolled eating. Summary More research on this topic is needed. Especially longitudinal studies using genetically sensitive designs to investigate the direction of genetic pathways between genetic liability of eating behaviours to weight and vice versa, as well as the potential subsequent link to eating disorders.

scholarly journals Impact of Abdominal Obesity on Thyroid Auto-Antibody Positivity: Abdominal Obesity Can Enhance the Risk of Thyroid Autoimmunity in Men

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Jazyra Zynat ◽  
Suli Li ◽  
Yanrong Ma ◽  
Li Han ◽  
Fuhui Ma ◽  
...  
Keyword(s):  
Waist Circumference ◽  
Abdominal Obesity ◽  
Thyroid Autoimmunity ◽  
Large Population ◽  
Overweight And Obesity ◽  
Thyroid Peroxidase ◽  
Hip Circumference ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Logistic Analysis

Background. The interrelation between obesity and autoimmune thyroid diseases is complex and has not been confirmed. The aim of the present study was to observe the relationship between thyroid autoimmunity and obesity, especially abdominal obesity, in a large population. Methods. A total of 2253 residents who had lived in Xinjiang for more than 3 years were enrolled. Serum thyroid hormone concentration, thyroid autoantibodies, lipid parameters, Weight, height, and waist and hip circumference were measured. Results. The prevalence of thyroid peroxidase antibody (TPOAb) and/or thyroglobulin antibody (TgAb) positive was 32.1% (21.2% in men and 37% in women, P<0.01). Compared with women, men had significantly higher TG levels, waist circumference, and hip circumference levels (P<0.01), while women showed higher TSH, TPOAb, and TgAb levels (P<0.01). The prevalence of overweight and obesity was 71.1% in men and 63.5% in women. Men had a higher prevalence of abdominal obesity than women (56.6% in men and 47.6% in women, P<0.01). TPOAb correlates positively with waist circumference (r = 0.100, P<0.05) in men. Binary logistic analysis showed that TPOAb positivity had increased risks of abdominal obesity in men, and the OR was 1.1044 (95% CI 1.035, 1.151, P<0.05). Conclusion. Our results indicate that men had higher lipid levels, thicker waist circumference, and higher prevalence of overweight, obesity, and abdominal obesity. Abdominal obesity is a risk factor for TPOAb positivity in men, suggesting that abdominal obesity can enhance the risk of thyroid autoimmunity in men.

Hydrogen peroxide-induced production of a 40 kDa immunoreactive thyroglobulin fragment in human thyroid cells: the onset of thyroid autoimmunity?

2001 ◽  
Vol 360 (3) ◽  
pp. 557-562 ◽  
Author(s):  
Christine DUTHOIT ◽  
Valérie ESTIENNE ◽  
Annie GIRAUD ◽  
Josée-Martine DURAND-GORDE ◽  
Åse Krogh RASMUSSEN ◽  
...  
Keyword(s):  
Culture Medium ◽  
Thyroid Autoimmunity ◽  
Culture Conditions ◽  
Autoimmune Response ◽  
Human Thyroid ◽  
Thyroid Cells ◽  
Autoimmune Thyroid ◽  
Hormone Synthesis ◽  
Immunodominant Region

We recently reported that, during in vitro thyroid-hormone synthesis, H2O2 stress cleaved thyroglobulin (Tg) into C-terminal peptides. These peptides were found to contain the immunodominant region of Tg recognized by Tg autoantibodies from patients with an autoimmune thyroid disease. To test the hypothesis that Tg fragmentation is an early upstream initiating event involved in Tg autoimmune response and the consequence of oxidative injuries, we studied the effect of H2O2 stress on human thyroid cells. In culture conditions allowing Tg synthesis and iodine organification by the cells, we found that bolus addition of increasing millimolar doses of H2O2 induced a dose–response appearance of floating cells in the culture medium. These cells apparently resulted from a necrotic process, and they bore iodinated Tg fragments. These fragments were found to be similar to those previously obtained in vitro from purified Tg. In both cases, Tg peptides were recognized by a well-defined monoclonal antibody directed to the immunodominant region of Tg. The smallest immunoreactive Tg peptide had a molecular mass of 40kDa and entered human thyrocytes more efficiently than the entire Tg. These data suggest that thyrocytes exposed to locally increased H2O2 doses accumulate fragmented Tg for further delivery into surrounding living thyrocytes in the course of an autoimmune response.

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