Association of the blood serum cytokines rate and lymphocytes apoptosis with polymorphic variants of the BCL-2 (rs17759659), CTLA-4 (rs231775) and APO-1/FAS (rs2234767) genes in patients with nodular goiters in autoimmune thyroiditis and thyroid adenoma

Vol. 58 No. 3, 2017

ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Michael Ivanovich Sheremet, Larysa Petrivna Sydorchuk, Viktor Oleksandrovych Shidlovskyi, Ruslan Igorovych Sydorchuk, Oleksandr Viktorovych Shidlovskyi, Vitaliy Vasilyovich Maksymyuk, Volodymyr Volodymyrovych Bezruk, Nina Petrivna Tkachuk, Viktor Markiyanovich Batig, Oleksandr Viktorovych Mytchenok, Tetyana Oleksandrivna Bezruk, Kristina Andreyvna Chympoi

The paper analyses results of serum cytokines and lymphocyte apoptosis study in patients with nodular goiter against the background of autoimmune thyroiditis (NGAIT) and thyroid adenoma (TA) based on the cell preparedness to apoptosis (content of lymphocytes carrying apoptosis marker - CD95+-receptor), the number of apoptotic lymphocytes (annexin V+-lymphocytes) and the content of proapoptotic tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6, as well as anti-inflammatory IL-4 cytokine in serum, considering the polymorphism of BCL-2 (rs17759659), CTLA-4 (rs231775) and APO-1/FAS (rs2234767) genes. The results show that under the damaging action of peroxidation products in the thyroid structures, activation of Fas- and caspase-dependent mechanisms of influence on pro- and anti-apoptotic targets, the induced hyperproduction and release of TNF-alpha from thyroid-stimulated lymphocytes stimulate an additional synthesis of other pro-inflammatory cytokines IL-1beta and IL-6, as well as compensatory anti-inflammatory proteins including IL-4. There is a synchronized increase in secretion of the soluble form of TNF-alpha receptor (sTNFR), which prevents binding the corresponding cytokine to a specific membranous shedding of a number of receptors and separates the apoptotic signals. The above-mentioned changes associate with the polymorphic variants of BCL-2 (rs17759659), CTLA-4 (rs231775) genes and only for some figures, they are almost three times weaker with FAS (rs2234767).

Corresponding author: Michael Ivanovich Sheremet, Assistant Professor, MD, PhD; e-mail: mihayl71@gmail.com

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