scholarly journals Structural studies of thyroid peroxidase show the monomer interacting with autoantibodies in thyroid autoimmune disease

2019 ◽  
Author(s):  
Daniel E. Williams ◽  
Sarah N. Le ◽  
David E. Hoke ◽  
Peter G. Chandler ◽  
Monika Gora ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Thyroid Peroxidase ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Structural Characterisation ◽  
Negative Stain ◽  
Thyroid Autoimmune Disease ◽  
Negative Stain Electron Microscopy ◽  
Membrane Bound ◽  
Dynamics Simulations

AbstractThyroid peroxidase (TPO) is a critical membrane-bound enzyme involved in the biosynthesis of multiple thyroid hormones, and is a major autoantigen in autoimmune thyroid diseases such as Graves’ disease and Hashimoto’s thyroiditis. Here we report the biophysical and structural characterisation of two novel TPO constructs containing only the ectodomain of TPO and lacking the propeptide. Both constructs were enzymatically active and able to bind the patient-derived TR1.9 autoantibody. Analytical ultra-centrifugation data suggests that TPO can exist as both a monomer and a dimer. Combined with negative stain electron microscopy and molecular dynamics simulations, these data show that TR1.9 autoantibody preferentially binds the TPO monomer, revealing conformational changes that bring together previously disparate residues into a continuous epitope. In addition to providing plausible structural models of a TPO-autoantibody complex, this study provides validated TPO constructs that will facilitate further characterization, and advances our understanding of the structural, functional and antigenic characteristics of TPO, a molecule behind some of the most common autoimmune diseases.

scholarly journals Structural Studies of Thyroid Peroxidase Show the Monomer Interacting With Autoantibodies in Thyroid Autoimmune Disease

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Daniel E Williams ◽  
Sarah N Le ◽  
David E Hoke ◽  
Peter G Chandler ◽  
Monika Gora ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Analytical Ultracentrifugation ◽  
Hashimoto Thyroiditis ◽  
Thyroid Peroxidase ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Negative Stain ◽  
Negative Stain Electron Microscopy ◽  
Membrane Bound ◽  
Dynamics Simulations

Abstract Thyroid peroxidase (TPO) is a critical membrane-bound enzyme involved in the biosynthesis of multiple thyroid hormones, and is a major autoantigen in autoimmune thyroid diseases such as destructive (Hashimoto) thyroiditis. Here we report the biophysical and structural characterization of a novel TPO construct containing only the ectodomain of TPO and lacking the propeptide. The construct was enzymatically active and able to bind the patient-derived TR1.9 autoantibody. Analytical ultracentrifugation data suggest that TPO can exist as both a monomer and a dimer. Combined with negative stain electron microscopy and molecular dynamics simulations, these data show that the TR1.9 autoantibody preferentially binds the TPO monomer, revealing conformational changes that bring together previously disparate residues into a continuous epitope. In addition to providing plausible structural models of a TPO-autoantibody complex, this study provides validated TPO constructs that will facilitate further characterization, and advances our understanding of the structural, functional, and antigenic characteristics of TPO, an autoantigen implicated in some of the most common autoimmune diseases.

scholarly journals Molecular mechanism of mitochondrial phosphatidate transfer by Ups1

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Jiuwei Lu ◽  
Chun Chan ◽  
Leiye Yu ◽  
Jun Fan ◽  
Fei Sun ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Mitochondrial Membrane ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Membranes ◽  
Inner Mitochondrial Membrane ◽  
Membrane Interaction ◽  
Detailed Mechanism ◽  
Physiological Regulator ◽  
Membrane Bound ◽  
Dynamics Simulations

AbstractCardiolipin, an essential mitochondrial physiological regulator, is synthesized from phosphatidic acid (PA) in the inner mitochondrial membrane (IMM). PA is synthesized in the endoplasmic reticulum and transferred to the IMM via the outer mitochondrial membrane (OMM) under mediation by the Ups1/Mdm35 protein family. Despite the availability of numerous crystal structures, the detailed mechanism underlying PA transfer between mitochondrial membranes remains unclear. Here, a model of Ups1/Mdm35-membrane interaction is established using combined crystallographic data, all-atom molecular dynamics simulations, extensive structural comparisons, and biophysical assays. The α2-loop, L2-loop, and α3 helix of Ups1 mediate membrane interactions. Moreover, non-complexed Ups1 on membranes is found to be a key transition state for PA transfer. The membrane-bound non-complexed Ups1/ membrane-bound Ups1 ratio, which can be regulated by environmental pH, is inversely correlated with the PA transfer activity of Ups1/Mdm35. These results demonstrate a new model of the fine conformational changes of Ups1/Mdm35 during PA transfer.

scholarly journals Thyroid Peroxidase Revisited – Whatʼs New?

2019 ◽  
Vol 51 (12) ◽  
pp. 765-769 ◽  
Author(s):  
Marlena Godlewska ◽  
Damian Gawel ◽  
Ashley M. Buckle ◽  
J. Paul Banga
Keyword(s):  
Thyroid Hormone ◽  
Environmental Factors ◽  
Recent Progress ◽  
Thyroid Peroxidase ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Thyroid Hormone Biosynthesis ◽  
Hormone Biosynthesis ◽  
Genetic And Environmental Factors ◽  
Thyroid Dysfunctions

AbstractThyroid peroxidase (TPO) is an enzyme that participates in thyroid hormone biosynthesis. TPO is also a major autoantigen in autoimmune thyroid diseases (AITD). In this review, we summarize the latest developments in the field of TPO research. We present the current understanding of immunodominant serologic determinants, frequency of TPO-specific autoantibodies in the population, as well as genetic and environmental factors contributing to their development. Moreover, we report recent progress in the clinical utilities of TPO autoantibody testing, including thyroid dysfunctions and extra-thyroidal disorders.

The human anti-thyroid peroxidase autoantibody repertoire in Graves' and Hashimoto's autoimmune thyroid diseases

2002 ◽  
Vol 54 (3) ◽  
pp. 141-157 ◽  
Author(s):  
Thierry Chardès ◽  
Nicolas Chapal ◽  
Damien Bresson ◽  
Cédric Bès ◽  
Véronique Giudicelli ◽  
...  
Keyword(s):  
Thyroid Diseases ◽  
Thyroid Peroxidase ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

scholarly journals Smoking is negatively associated with the presence of thyroglobulin autoantibody and to a lesser degree with thyroid peroxidase autoantibody in serum: a population study

2008 ◽  
Vol 158 (3) ◽  
pp. 367-373 ◽  
Author(s):  
Inge Bülow Pedersen ◽  
Peter Laurberg ◽  
Nils Knudsen ◽  
Torben Jørgensen ◽  
Hans Perrild ◽  
...  
Keyword(s):  
Population Study ◽  
Age Groups ◽  
Negative Association ◽  
Thyroid Peroxidase ◽  
Thyroid Autoantibodies ◽  
Thyroid Antibodies ◽  
Autoimmune Thyroid Diseases ◽  
Cross Sectional ◽  
Negatively Associated ◽  
Autoimmune Thyroid

BackgroundAutoimmune thyroid diseases are common and the prevalence of circulating thyroid antibodies (thyroid peroxidase antibody, TPO-Ab and thyroglobulin antibody, Tg-Ab) is high in the population. The knowledge of a possible association between lifestyle factors and circulating thyroid antibodies is limited.AimTo evaluate the correlation between smoking habits and the presence of circulating TPO-Ab and Tg-Ab.Material and methodsIn a cross-sectional comparative population study performed in two areas of Denmark with moderate and mild iodine deficiency, 4649 randomly selected subjects from the population in some predefined age groups between 18 and 65 years were examined. Blood tests were analysed for TPO-Ab and Tg-Ab using assays based on the RIA technique. The participants answered questionnaires, were clinically examined and blood and urine samples collected.ResultsData were analysed in multivariate logistic regression models. There was a negative association between smoking and the presence of thyroid autoantibodies in serum. This association was observed for the presence of TPO-Ab and/or Tg-Ab, TPO-Ab (without respect to Tg-Ab status), Tg-Ab (without respect to TPO-Ab status) and both antibodies together. The association between smoking and thyroid autoantibodies was stronger for Tg-Ab than for TPO-Ab. There was no association between smoking and TPO-Ab measured alone or between smoking and TPO-Ab when Tg-Ab was included in the model as an explanatory variable.ConclusionSmoking was negatively associated with the presence of thyroid autoantibodies with the strongest association between smoking and Tg-Ab. The study design precludes any conclusions as to the cause of the negative association between smoking thyroid autoantibodies.

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.

scholarly journals Prevalence of Thyroid Abnormalities in Thai Patients with Vitiligo

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Vasanop Vachiramon ◽  
Sarawin Harnchoowong ◽  
Woranit Onprasert ◽  
Kumutnart Chanprapaph
Keyword(s):  
Thyroid Function Test ◽  
Female Gender ◽  
Thyroid Diseases ◽  
Thyroid Peroxidase ◽  
Thyroid Antibodies ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Dermatology Clinic ◽  
Thyroid Abnormalities ◽  
Serum Tsh

Background. Vitiligo is an acquired hypopigmentary disorder. The prevalence of vitiligo is 0.1–2% worldwide. Numerous autoimmune diseases are associated with vitiligo, including autoimmune thyroid diseases. The prevalence of thyroid abnormalities is up to 34% in vitiligo patients depending on ethnicities. Objective. This study aims to investigate thyroid abnormalities in Thai patients with vitiligo. Methods. Medical records of vitiligo patients attending outpatient dermatology clinic at a university-based hospital from 2012 to 2016 were retrospectively reviewed. Data regarding vitiligo, clinical features, and autoimmune thyroid laboratory results were retrieved and analyzed. Results. Among 325 vitiligo patients identified, anti-thyroid peroxidase and anti-thyroglobulin were positive in 90 (27.7%) and 63 patients (19.4%), respectively. Positive thyroid antibody was associated with female gender (p<0.001) and vitiliginous hand lesions (p<0.02). Out of 197 patients with complete thyroid function test, the prevalence of autoimmune thyroid diseases (AITD) is 12.7%. Female, nonsegmental type, higher affected area, and the presence of leukotrichia are significantly associated with AITD in vitiligo patients. Conclusions. Prevalence of positive thyroid antibodies and AITD in Thai patients with vitiligo is compatible with previous studies around the world. Screening for AITD with thyroid antibodies and serum TSH is essential for vitiligo patients.

Longitudinal Associations Between TPO Gene Variants and TPOAb Seroconversion In A Population Based Study: Tehran Thyroid Study (TTS)

2021 ◽  
Author(s):  
Amir Hossein Ghanooni ◽  
Azita Zadeh-Vakili ◽  
Boshra Rezvankhah ◽  
Somayeh Jafari Nodushan ◽  
Mahdi Akbarzadeh ◽  
...  
Keyword(s):  
Predictive Marker ◽  
Population Based ◽  
Control Group ◽  
Thyroid Peroxidase ◽  
Gene Variants ◽  
Thyroid Antibodies ◽  
Genetic Determinants ◽  
Autoimmune Thyroid Diseases ◽  
Cross Sectional ◽  
Autoimmune Thyroid

Abstract Background: Autoimmune thyroid diseases (AITD) are among the most common autoimmune diseases in the world. They are usually accompanied by the presence of anti-thyroid antibodies as the early predictive marker. Genetic determinants of the susceptibility to develop thyroid antibodies are still poorly understood. This study aimed to investigate the relation between thyroid peroxidase (TPO) gene variants (53 SNPs) and positive TPOAb and also to evaluate the effect of some environmental factors on changes from negative to positive TPOAb (Seroconversion). Methods: Participants from the Tehran Thyroid Study (TTS) in phases 1 and 2 (N=5317, ≥ 20 years) were evaluated for the positive TPOAb and its relationship with 53 SNPs from TPO gene (a cross-sectional approach). At the second stage of the study (a longitudinal approach), negative TPOAb participants (control group, N= 4815) were followed up for about 5.5 (5.54±1.62) years until they have had positive results for TPOAb (“TPOAb seroconversion”). The association between TPO gene polymorphisms and TPOAb seroconversion was evaluated using logistic regression analysis and SKAT (sequence kernel association test) package. Results: In cross-sectional analyses, 17 SNPs were associated with TPOAb positivity (521 positive TPOAb participants) after the adjustment for age, sex, body mass index (BMI), smoking, the number of parity and oral contraceptive consumption (P <0.05). In longitudinal analyses, there was an association between TPOAb seroconversion and four SNPs before, and three SNPs after adjustment (P <0.05). Conclusions: TPOAb seroconversion could be affected by some thyroid peroxidase gene variants.

Sign in / Sign up

Export Citation Format

Share Document