IMMUNOLOGICAL PARAMETERS IN PATIENTS WITH CHRONIC OPISTHORCHIASIS BEARING GENE MUTATIONS ASSOCIATED WITH OSTEOPOROSIS-PREDISPOSITION

L. Kurlaeva, T. F. Stepanova, Ksenia Stepanova, A. N. Kosyreva, Irina Vladimirovna Bakshtanovskaya, G. Kalgina, Svetlana Andreevna Grigorieva
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Abstract

To identify the features of the immune system functioning in patients with chronic opisthorchiasis bearing mutations in loci associated with predisposition to developing osteoporosis, comprehensive studies of cellular and humoral arms were carried out. The state of the phagocytic system was assessed by assessing absorption, metabolic activity and reactive oxygen species formation to restore nitrosine tetrazolium (spontaneous and stimulated NST test). The phenotype of lymphocytes was determined by flow cytometry. The humoral immune arm was evaluated by the number of immunoglobulin classes M, G, A and E. Differences in the functional state of various arms of the immune system were revealed. In patients with chronic opisthorchiasis in the presence of rs1544410 polymorphism of the gene encoding the intracellular vitamin D receptor, the relative number of T-helper cells is significantly lower than in the group with the normal allele. In the presence of rs1800012 polymorphism of the gene encoding the 1-chain of type I collagen, the absolute lymphocyte count is significantly higher, spontaneous and stimulated NST test were lower, the number of DN-T lymphocytes is significantly lower (both in relative and absolute values). In the presence of the rs3736228 mutation of the gene encoding the transmembrane low-density lipoprotein receptor, the level of myeloperoxidase and the neutrophil stimulation index are lower, the absorption activity of neutrophils is higher. The presence of the rs2234693 mutation for estrogen receptor gene leads to significantly increased level of stimulated NST test and IgG concentration. Thus, patients with chronic opisthorchiasis bearing mutations in the COL1 A1, LRP5, ESR1(rs2234693) genes, have altered both nonspecific innate reactions and parameters of the adaptive immune arm; mutation of the VDR gene s9lely affects adaptive immunity. Analysis of the results suggests that the presence of mutations associated with the development of osteoporosis has a modulating effect on the immune response in chronic opisthorchiasis invasion. The identification of polymorphic genes associated with metabolic disorders of bone tissue and the study of the immunological profile in patients with chronic opisthorchiasis invasion will allow to implement an individual approach in the treatment of such patients.
与骨质疏松症易感性相关的基因突变的慢性口蹄疫患者的免疫学参数
为了确定与骨质疏松症易感性相关的基因位点突变的慢性口蹄疫患者的免疫系统功能特征,对细胞和体液武器进行了全面研究。通过评估吸收、新陈代谢活动和活性氧形成以恢复亚硝酸四氮唑(自发和刺激 NST 试验),对吞噬系统的状态进行了评估。淋巴细胞的表型通过流式细胞术确定。体液免疫臂通过 M、G、A 和 E 类免疫球蛋白的数量进行评估。在存在细胞内维生素 D 受体编码基因 rs1544410 多态性的慢性口蹄疫患者中,T 辅助细胞的相对数量明显低于正常等位基因组。在编码 I 型胶原 1 链的基因存在 rs1800012 多态性的情况下,淋巴细胞绝对数量明显增加,自发和刺激 NST 试验均降低,DN-T 淋巴细胞数量明显降低(包括相对值和绝对值)。编码跨膜低密度脂蛋白受体的基因出现 rs3736228 突变时,髓过氧化物酶水平和中性粒细胞刺激指数较低,中性粒细胞的吸收活性较高。雌激素受体基因 rs2234693 突变会导致刺激 NST 试验水平和 IgG 浓度显著升高。因此,COL1 A1、LRP5、ESR1(rs2234693)基因突变的慢性口蹄疫患者的非特异性先天性反应和适应性免疫臂参数都发生了改变;VDR基因突变仅影响适应性免疫。分析结果表明,与骨质疏松症的发生有关的突变的存在对慢性鸦片吸虫病入侵的免疫反应有调节作用。通过鉴定与骨组织代谢紊乱有关的多态性基因和研究慢性弓形虫入侵患者的免疫学特征,可以对这类患者采取个性化的治疗方法。
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