ISSN 2415-3060 (print), ISSN 2522-4972 (online)
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УЖМБС 2022, 7(1): 292–299

Мolecular Mechanisms of Pathogenesis of Autoimmune Нashimoto's Thyroiditis (Literature Review)

Holieva H. Yu. 1,2

The purpose of the study was to systematize and analyze material of recent studies on molecular mechanisms of pathogenesis of autoimmune Hashimoto's thyroiditis. Materials and methods. Analytical and bibliosemantic methods were used in the study. Results and discussion. Autoimmune Hashimoto's thyroiditis is a chronic inflammatory disease of the thyroid gland of autoimmune genesis in which impaired tolerance to thyroid autoantigens results in chronic progressive lymphoid infiltration followed by gradual destruction of thyroid parenchyma. The disease is more often observed at the age of 45-65 years and is multifactorial – both genetic predisposition and environmental factors contribute to its development. The ratio of female to male patients is approximately 10-20:1, and in recent years, the prevalence of autoimmune Hashimoto's thyroiditis has increased more than tenfold. On morphological examination, the section of the thyroid is diffusely enlarged, the surface of the section is pale, yellow-brown in color, dense and nodular. Microscopic examination reveals numerous large mononuclear inflammatory infiltrates in the parenchyma, consisting of small lymphocytes and plasma cells, well-formed germinal centers. A twin method is used to assess the degree of contribution of genetic and environmental factors. Studies demonstrate significantly greater concordance in monozygotic twins than in dizygotic twins, confirming the important role of genetic factors in the etiology. Among the main immune mechanisms of damage are: direct action of CD8+ cytotoxic T cells on thyrocytes by binding through the Fas-receptor – Fas ligand system; the influence of cytokines, in particular – interferon γ, produced by TH1 cells and leading to macrophage activation with subsequent damage to follicles, antibody-dependent cell-mediated cytotoxicity, in which Fc fragments of antibodies previously bound to thyroid cells are binding sites to cells that commit killing, in particular – to the natural killer cells. In terms of thyroid cell damage, cytokines produced by the lymphocytic infiltrate play a key role. These include differentiation, signal transduction, and stimulation of other cells to release proinflammatory mediators or synthesize antibodies. Their ability to stimulate the thyroid cells themselves to release inflammatory mediators should be noted, thereby enhancing and perpetuating the autoimmune process. Researchers have identified other mechanisms, and the ratio of their contribution to the overall pathological process is a matter of debate and may vary from patient to patient. One explanation may be the multifactorial nature of the disease. In particular, different genetic mutations can lead to different disorders of intracellular and intercellular signaling, but the resulting factor will be one – immune autoaggression. Conclusion. The pathogenesis of autoimmune Hashimoto's thyroiditis is complex and multifaceted, involving both humoral and cellular immunity. The disease may be provoked both by mutations in the mechanisms of immune regulation, by mutations in the thyroid cells themselves, and by environmental factors

Keywords: autoimmune Hashimoto's thyroiditis, thyroid, autoantigens, immune mechanisms of damage, autoantibodies, thyrocytes, autoimmune disease, thyroid hormone, lymphocytes, interleukins

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