Screening for Subclinical Autoimmune Thyroid Diseases with Highly Sensitive Assays for Autoantibodies to Thyroglobulin and Thyroid Peroxidase and Serum Thyrotropin Concentrations

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.

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Detection of Autoantibodies to Thyroid Peroxidase in Autoimmune Thyroid Diseases by Micro-ELISA and Immunoblotting*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem-62-5-928 ◽

1986 ◽

Vol 62 (5) ◽

pp. 928-933 ◽

Cited By ~ 73

Author(s):

TOMIO KOTANI ◽

KAZUMI UMEKI ◽

SEIJI MATSUNAGA ◽

EIICHI KATO ◽

SACHIYA OHTAKI

Keyword(s):

Thyroid Diseases ◽

Thyroid Peroxidase ◽

Autoimmune Thyroid Diseases ◽

Autoimmune Thyroid

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The role of hereditary and environmental factors in autoimmune thyroid diseases

Orvosi Hetilap ◽

10.1556/oh.2012.29370 ◽

2012 ◽

Vol 153 (26) ◽

pp. 1013-1022 ◽

Cited By ~ 14

Author(s):

Csaba Balázs

Keyword(s):

Environmental Factors ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Thyroid Autoimmunity ◽

Thyroid Diseases ◽

Thyroid Peroxidase ◽

Autoimmune Thyroid Diseases ◽

Autoimmune Thyroid ◽

Histocompatibility Complex

Autoimmune thyroid diseases are the most common organ-specific autoimmune disorders affecting 5% to 10% of the population in Western countries. The clinical presentation varies from hyperthyroidism in Graves’ disease to hypothyroidism in Hashimoto’s thyroiditis. While the exact etiology of thyroid autoimmunity is not known, the interaction between genetic susceptibility and environmental factors appears to be of fundamental importance to initiate the process of thyroid autoimmunity. The identified autoimmune thyroid disease susceptibility genes include immune-modulating genes, such as the major histocompatibility complex, and thyroid-specific genes, including TSH receptor, thyroglobulin and thyroid peroxidase. The majority of the anti-TSH-receptor antibodies have a stimulating capacity and are responsible for hyperthyroidism. The anti-thyroglobulin- and anti-thyroid peroxidase antibodies belonging to the catalytic type of antibodies destroy the thyrocytes resulting in hypothyroidism. The appearance of anti-thyroid peroxidase antibodies precedes the induction of thyroiditis and the manifestation of hypothyroidism. The molecular analysis of thyroglobulin gene polymorphism is important in the mechanism of autoimmune thyroiditis. The autoantigen presentation by major histocompatibility complex molecules is a key point of the autoimmune mechanism. It has been shown that a HLA-DR variant containing arginine at position 74 of the DRβ1 chain confers a strong genetic susceptibility to autoimmune thyroid diseases, Graves’ disease and Hashimoto’s thyroiditis, while glutamine at position DRβ1-74 is protective. Human thyroglobulin 2098 peptide represents a strong and specific DRβ1-Arg74 binder, while a non-binding control peptide, thyroglobulin 2766 fails to induce this response. Moreover, thyroglobulin 2098 stimulated T-cells from individuals who were positive for thyroglobulin antibodies, demonstrating that thyroglobulin 2098 is an immunogenic peptide capable of being presented in vivo and activating T-cells in autoimmune thyroid diseases. Taken together these findings suggest that thyroglobulin 2098, a strong and specific binder to the disease-associated HLA-DRβ1-Arg74, is a major human T-cell epitope and it participates in the pathomechanism of the autoimmune thyroid disease. The exact nature of the role of environmental factors in the autoimmune thyroid disease is still not well known, but the importance of several factors such as iodine, drugs and infections has been reported. Further knowledge of the precise mechanisms of interaction between environmental factors and genes in inducing thyroid autoimmunity could result in the development of new strategies for diagnosis, prevention and treatment. Orv. Hetil., 2012, 153, 1013–1022.

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Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases

Cells ◽

10.3390/cells9030665 ◽

2020 ◽

Vol 9 (3) ◽

pp. 665 ◽

Cited By ~ 3

Author(s):

Tiphaine C. Martin ◽

Kristina M. Ilieva ◽

Alessia Visconti ◽

Michelle Beaumont ◽

Steven J. Kiddle ◽

...

Keyword(s):

Genetic Variants ◽

Immune Cell ◽

Nk Cell ◽

Killer Cell ◽

Thyroid Diseases ◽

Thyroid Peroxidase ◽

Autoimmune Thyroid Diseases ◽

Altered Expression ◽

Germline Variants ◽

Autoimmune Thyroid

The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood and the association between different immune features and the germline variants involved in AITD are yet unclear. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation in peripheral blood mononuclear cells in AITD, correlated with anti-thyroid peroxidase antibody (TPOAb) levels. Fucose depletion is known to potentiate strong antibody-mediated NK cell activation and enhanced target antigen-expressing cell killing. In autoimmunity, this may translate to autoantibody-mediated immune cell recruitment and attack of self-antigen expressing normal tissues. Hence, we investigated the crosstalk between immune cell traits, secreted proteins, genetic variants and the glycosylation patterns of serum IgG, in a multi-omic and cross-sectional study of 622 individuals from the TwinsUK cohort, 172 of whom were diagnosed with AITD. We observed associations between two genetic variants (rs505922 and rs687621), AITD status, the secretion of Desmoglein-2 protein, and the profile of two IgG N-glycan traits in AITD, but further studies need to be performed to better understand their crosstalk in AITD. On the other side, enhanced afucosylated IgG was positively associated with activatory CD335- CD314+ CD158b+ NK cell subsets. Increased levels of the apoptosis and inflammation markers Caspase-2 and Interleukin-1α positively associated with AITD. Two genetic variants associated with AITD, rs1521 and rs3094228, were also associated with altered expression of the thyrocyte-expressed ligands known to recognize the NK cell immunoreceptors CD314 and CD158b. Our analyses reveal a combination of heightened Fc-active IgG antibodies, effector cells, cytokines and apoptotic signals in AITD, and AITD genetic variants associated with altered expression of thyrocyte-expressed ligands to NK cell immunoreceptors. Together, TPOAb responses, dysregulated immune features, germline variants associated with immunoactivity profiles, are consistent with a positive autoreactive antibody-dependent NK cell-mediated immune response likely drawn to the thyroid gland in AITD.

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Comparison of thyroglobulin and thyroid peroxidase antibodies measured by five different kits in autoimmune thyroid diseases

Endocrine Journal ◽

10.1507/endocrj.ej17-0164 ◽

2017 ◽

Vol 64 (10) ◽

pp. 955-961 ◽

Cited By ~ 3

Author(s):

Eijun Nishihara ◽

Nobuyuki Amino ◽

Takumi Kudo ◽

Mitsuru Ito ◽

Shuji Fukata ◽

...

Keyword(s):

Thyroid Diseases ◽

Thyroid Peroxidase ◽

Autoimmune Thyroid Diseases ◽

Autoimmune Thyroid ◽

Thyroid Peroxidase Antibodies

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Association Study of the Thyroid Peroxidase Gene in Autoimmune Thyroid Diseases

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1707 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A836-A837

Author(s):

Yoshiyuki Ban ◽

Teruaki Tozaki ◽

Shinichi Iwai

Keyword(s):

Association Study ◽

Japanese Population ◽

Japanese Patients ◽

Case Control ◽

Thyroid Diseases ◽

Taqman Probe ◽

Thyroid Peroxidase ◽

Autoimmune Thyroid Diseases ◽

Autoimmune Thyroid ◽

Control Association

Abstract Introduction: The etiology of autoimmune thyroid diseases (AITDs), such as Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), is largely unknown. However, genetic susceptibility is believed to play a major role. Recently, a case-control association study performed in Croatia showed a significant association of the single nucleotide polymorphism (SNP) rs11675434 near thyroid peroxidase (TPO) with HT, and also with thyroid autoantibodies against TPO (TPOAb) levels. High TPOAb levels are present in 90% of patients with HT and serve as a clinical marker for the detection of early AITD/HT. Therefore, we conducted a case-control study to determine the genetic association of the rs11675434 near TPO with AITD in a cohort of the Japanese population. Methods: We genotyped the rs11675434 near TPO in 457 Japanese patients with AITD (286 with GD, 171 with HT) and 242 matched Japanese control subjects. The SNP was analyzed using TaqMan probe method, and association study was performed using the χ 2 and Fisher’s exact tests with Yates correction. Results: Both GD and HT showed no significant associations. Moreover, when patients with GD were stratified according to Graves’ ophthalmopathy (GO) (n=96), there were no allelic associations with GO, although there were weak associations between GO and controls (P=0.0494, Odds ratios (ORs)=0.3102). Conclusions: Our finding suggest that the rs11675434 near TPO may not contribute to the risk of AITD in the Japanese population, although the study was in insufficient and underpowered sample size.

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The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid diseases

Beneficial Microbes ◽

10.3920/bm2010.0011 ◽

2011 ◽

Vol 2 (2) ◽

pp. 139-154 ◽

Cited By ~ 20

Author(s):

E. Kiseleva ◽

K. Mikhailopulo ◽

O. Sviridov ◽

G. Novik ◽

Y. Knirel ◽

...

Keyword(s):

Molecular Mechanisms ◽

Molecular Mimicry ◽

Thyroid Diseases ◽

Whole Body ◽

Thyroid Peroxidase ◽

Autoimmune Thyroid Diseases ◽

Bifidobacterium Adolescentis ◽

Autoimmune Thyroid ◽

Antigenic Properties

During recent years, researchers have been focusing on the concept of an infectious etiology of autoimmune diseases. The most discussed theory is molecular mimicry, i.e. the emergence of autoreactive clones of T- and B-lymphocytes as a result of cross-immune response to homologous bacterial or viral antigen. Information on the role of probiotic microorganisms (PM) in the molecular mechanisms of autoimmune thyroid diseases (ATD) is limited. Using proteins and immunogenic peptides databanks and relevant computer programs, the homology between the amino acid sequences of thyroid peroxidase (TPO) and thyroglobulin (Tg), which are potential B- and T-cell epitopes of these antigens, and proteins of bifidobacteria and lactobacilli was established. Moreover, we have found components of cells of Bifidobacterium bifidum 791, Bifidobacterium adolescentis 94 BIM, Bifidobacterium longum B379M and Lactobacillus plantarum B-01 that selectively bind human antibodies to TPO (anti-TPO) and antibodies to Tg (anti-Tg) and compete with natural antigens for the binding of anti-TPO and anti-Tg in ELISA. Additionally, a three-fold difference was observed between the probability of detecting antibodies (Abs) to the antigens of L. plantarum B-01 and B. bifidum 791 in serum samples containing and those not containing anti-TPO. On the whole, our data are arguments in favour of the assumption of the possible role of PM of the genera Bifidobacterium and Lactobacillus in triggering ATD by the mechanism of molecular mimicry. The data obtained in silico and in vitro should be proven by use of animal models and clinical studies for extrapolations to the whole body. Possible antigenic properties of components/proteins of bifidobacteria and lactobacilli, selectively binding anti-TPO and anti-Tg should be taken into consideration. Natural human Abs to these bacterial components are probably able to cross-react with the TPO and Tg in the ELISA for detection of anti-TPO and anti-Tg, which are serologic markers of ATD. It can lead to unspecific false positive results and, hence, to an incorrect diagnosis.

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