Auto immune thyroid disease: The pathogenesis of Graves disease and Hashimoto thyroiditis

Abstract

It is generally accepted that autoimmune thyroid disorders, Graves disease and Hashimoto thyroiditis, differ in pathogenesis and clinical implications. In Graves disease the basic pathogenetic mechanism is B lymphocyte activation which produce auto antibodies specific for TSH receptor (TSHR) which binding to thyrocyte membrane causes their long-termed stimulation which gives as a result the occurrence of hyperthyrosis. On the other hand in Hashimoto thyroiditis lymphocyte accumulation occurs and they cause gradual thyrocyte damage and hypothyrosis development. However, it was found that the reisa certain genetic predisposition for both autoimmune thyroid diseases and that they can appear among several members of the same family. Besides in the serum of the patients with Graves disease and Hashimoto thyroiditis the presence of autoantibodi esspecific for dominant thyroid autoantigenes: TSHR, thyroperoxidase (TPO) and thyroglobulin (Tg) can be found as indicators of the auto immune process in thyroid gland. For these reasons both autoimmune diseases of thyroid gland sometimes are marked with the common name: autoimmune thyroid disease. As cell and molecule mechanisms included in initiation of the autoimmune process in thyroid gland that define the type and natural course of disease have not completely been explained, in this review the data from the literature considering pathogenesis of autoimmune diseases of thyroid gland have been shown. After introductory considerations, dominant autoantigenes and autoantibodies (as indicators of autoimmune process in thyroid gland) are shown in details, as well as mechanisms included in effector phase of autoimmune process which cau se the thyroid cell damage. The role of disturbance in regulation of the apoptosis process is especially analyzed as they could effect the development of autoimmune diseases of thyroid gland.

Prihvaćeno je shvatanje da se autoimunske bolesti štitaste žlezde Graves-ova bolest i Hashimoto tireoiditis razlikuju po patogenezi i kliničkim posledicama. U Graves-ovoj bolesti je osnovni patogenetski mehanizam aktivacija Blimfocita koji produkuju auto antitela specifična za TSH receptor (TSHR), čije vezivanje za membranu tireocita uzrokuje njihovu dugotrajnu stimulaciju, sa posledičnim nastankom hipertireoze. S druge strane, u Hashimoto tireoiditi su nastaje akumulacija limfocita koji prouzrokuju postepeno oštećenje tireocita i nastanak hipotireoze. Međutim utvrđeno je da za obe autoimunske tireoidne bolesti postoji određena genetska predispozicija i da se one mogu javiti kod više članova u istoj porodici. Osim toga, u serumu obolelih od Graves-ove bolesti i Hashimoto tireoiditi sa se može pokazati prisustvo autoantitela specifičnih za dominantne tireoidne autoantigene (receptor za TSH, tireoperoksidazu i tireoglobulin) koji predstavljaju pokazatelje autoimunskog procesa u štitastoj žlezdi. Iz tih razloga se obe autoimunske bolesti štitaste žlezde nekad označavaju zajedničkim nazivom: autoimunska bolest štitaste žlezde. Budući da ćelijski i molekulski mehanizmi koji su uključeni u inicijaciju autoimunskog procesa u štita stoj žlezdi, i opredeljuju vrstu i prirodni tok bolesti, nisu potpuno rasvetljeni, u ovom radu su prikazani podaci iz literature koji se odnose na patogenezu autoimunskih bolesti štitaste žlezde. Nakon uvodnih razmatranja, detaljno su prikazani dominantni autoantigeni i autoantitela (kao pokazatelji autoimunskog procesa u štitastoj žlezdi), kao i mehanizmi uključeni u efektorsku fazu autoimunskog procesa koji uzrokuju oštećenje tireocita. Posebno je analizirana uloga poremećaja u regulaciji procesa apoptoze u nastanku autoimunskih bolesti štitaste žlezde.