scholarly journals Evolution of the views on pathogenesis of autoimmune thyroid diseases and prospects for their target therapy

2017 ◽  
Vol 95 (6) ◽  
pp. 524-534
Author(s):  
B. I. Gel’tser ◽  
V. V. Zdor ◽  
Vladimir N. Kotel’nikov
Keyword(s):  
Target Therapy ◽  
Animal Experiments ◽  
Local Effect ◽  
Thyroid Diseases ◽  
Thyroid Peroxidase ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Specific Receptors ◽  
Thyroid Autoantigens

Modern scientific literature contains few reports concerning the influence of target therapy on pathogenetic factors of autoimmune thyroid diseases (AITD). Despite a large number of hypotheses of AITD pathogenesis, the only well established fact is the starting stage of Graves disease (GD) and autoimmune thyroiditis (AIT) is the loss of tolerance to thyroid autoantigens and the final stage is production of autoantibodies to them. Up to 75-80% of the patients with GD have antibodies against thyroid peroxidase and only few of them have anti-thyroglobulin antibodies more characteristic of AIT. Thyrotropin releasing hormone (TRH) is known to stimulate T-lymphocyte production via local effect on insulin-like growth factor (IGF). Modern studies confirm the important role of cytokines in immunopathogenesis of GD and AIT. Moreover, excess activation of this system in AITD provides a basis for the development of specific therapeutic approaches to personified pharmacotherapy. The effectiveness of anti-cytokine therapy of GD and AIT was demonstrated in animal experiments. Studies of therapy targeted on orbital and thyroid autoantigens in AITD are currently underway. The existence of specific receptors and the ability of immunocompetent cells to produce neuropeptides create prerequisites for their participation in intercellular cooperative processes. It can be supposed, by analogy with the influence of hormones and neuromediators on immunocytes, that neurohormones act on them via specific receptors with the involvement of cyclic nucleotides. It opens up opportunity for targeted correction of these relationships. Further studies of immunopathogenetic mechanisms of GD and AIT for better understanding the role of interaction between inborn and acquired immunity, its regulation, and intersystem transmission of signals in the development of these diseases are needed to realize modern strategies of their target therapy.

scholarly journals The role of selenium in the pathogenesis of thyroid disease

2019 ◽  
Vol 14 (4) ◽  
pp. 192-205 ◽  
Author(s):  
Ekaterina A. Troshina ◽  
Evgeniya S. Senyushkina ◽  
Maria A. Terekhova
Keyword(s):  
Immune Response ◽  
Thyroid Disease ◽  
Animal Experiments ◽  
Optimal Level ◽  
Thyroid Diseases ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Increased Risk ◽  
Combined Deficiency

The past few years have been actively discussing the role of individual macro- and micronutrients as factors regulating the functional activity of organs and systems and reducing the risk of developing a number of diseases, including thyroid diseases. Selenium is one of the most important and intensively studied at present microelements. According to several studies, its low plasma level is associated with an increased risk of developing autoimmune thyroid diseases. In animal experiments, it was shown that a combined deficiency of selenium and iodine leads to more pronounced hypothyroidism than iodine deficiency alone. Some authors believe that cretinism in the newborn is a consequence of the combined deficiency of these two elements in the mother. It is also important that the optimal level of selenium is necessary both to initiate an immune response and to regulate an excessive immune response, as well as chronic inflammation. The review article discusses the relationship between selenium and thyroid pathology, discusses the role of selenium in the physiology of the thyroid gland and in the development of autoimmune diseases. The biochemical aspects of the pathogenesis of thyroid disease are presented.

The role of hereditary and environmental factors in autoimmune thyroid diseases

2012 ◽  
Vol 153 (26) ◽  
pp. 1013-1022 ◽  
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.

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

2011 ◽  
Vol 2 (2) ◽  
pp. 139-154 ◽  
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.

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

A potential role of TNFR gene polymorphisms in autoimmune thyroid diseases in the Tunisian population

Cytokine ◽  
2008 ◽  
Vol 43 (2) ◽  
pp. 110-113 ◽  
Author(s):  
Maha Kammoun-Krichen ◽  
Noura Bougacha-Elleuch ◽  
Kaouthar Makni ◽  
Mouna Mnif ◽  
Joumaa Jouida ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Potential Role ◽  
Thyroid Diseases ◽  
Tunisian Population ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

scholarly journals Role of the T and B lymphocytes in pathogenesis of autoimmune thyroid diseases

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Marta Rydzewska ◽  
Michał Jaromin ◽  
Izabela Elżbieta Pasierowska ◽  
Karlina Stożek ◽  
Artur Bossowski
Keyword(s):  
B Lymphocytes ◽  
Thyroid Diseases ◽  
T And B Lymphocytes ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

scholarly journals The role of common genetic markers in susceptibility to type 1 diabetes and autoimmune thyroid diseases

2011 ◽  
Vol 14 (2) ◽  
pp. 23-31 ◽  
Author(s):  
Ekaterina Alexandrovna Repina
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Markers ◽  
Current Data ◽  
Thyroid Diseases ◽  
Single Patient ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

This review generalizes current data on the genes responsible for combined susceptibility to type 1 diabetes and autoimmune thyroid diseases. Analysisof the role of common genetic markers facilitates understanding their contribution to the development of each of the two or several concomitantautoimmune diseases affecting a single patient

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.

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