持续性eb病毒感染再激活背景下治疗全身性自身免疫性疾病患者的有效性

K. Lishchuk-Yakymovych, I.H. Haiduchok, K. Ischeykin, V. Chopyak
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摘要

本文在持续eb病毒感染再激活的背景下,研究肌苷pranobex (IP)对系统性自身免疫性疾病(SAD)患者的疗效。380例SAD(系统性红斑狼疮、系统性血管炎、类风湿关节炎、牛皮癣)患者中,144例(37.9%)患者采用聚合酶链反应(PCR)技术在3种生物基质(血液、唾液、病变部位刮擦)中检测到持续性EBV感染的再激活。48例患者接受肌苷pranobex治疗,剂量为50mg /kg /天,持续3个月。通过研究miR-146、miR-155、miR- EBV (BART-13和BART-15)、TLR9的表达水平、淋巴细胞群和亚群的数量来控制治疗效果。经治疗后,PCR结果显示66.7%的病例病毒复制减少。使用IP可导致IgM、IgG特异性抗体水平显著降低,抗炎miR-146a表达水平升高,促炎miR-155表达水平降低,可能提示抗病毒控制的加强。研究数据显示miR EBV (BART-13和BART-15)和TLR9在免疫活性细胞上的表达减少,这也可归因于IP有效性标准。细胞机制的稳定也证明了IP的有效性,即T细胞和B细胞群的正常化趋势,自然杀伤细胞和活化细胞(CD25+, CD3+ HLA DR+)数量的减少。另一方面,具有抑制活性的淋巴细胞(CD4+25+)的数量仍然显著高,可减轻自身免疫攻击。本研究结果表明,使用IP治疗EBV急性期感染有助于降低病毒的复制活性;抑制自身免疫反应的侵袭性miR EBV (BART-13和BART-15)表达的减少可以作为IP有效性的标准;TLR9在免疫活性细胞上表达的减少-作为抑制自身免疫反应的标准。
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Effectiveness of treatment of patients with systemic autoimmune diseases on the background of reactivation of persistent Epstein-Barr virus infection
The article presents the study of effectiveness of inosine pranobex (IP) in patients with systemic autoimmune diseases (SAD) on the background of reactivation of persistent Epstein-Barr (EBV) infection. Among 380 patients with SAD (systemic lupus erythematosus, systemic vasculitides, rheumatoid arthritis, psoriasis), in 144 patients (37.9%) the reactivation of persistent EBV infection was detected through virus DNA identification using polymerase chain reaction (PCR) in three biological matrices (blood, saliva, scraping from the lesion site). 48 patients were receiving inosine pranobex at a dose of 50 mg/kg per day for three months. Treatment efficacy was controlled by studying the levels of expression of miR-146а, miR-155, miR EBV (BART-13 and BART-15), TLR9, the quantity of lymphocytes populations and subpopulations. After treatment, PCR results showed a decrease in viral replication in 66.7% of cases. The use of IP contributed to a significant decrease in the level of IgM, IgG specific antibodies, an increase in the level of expression of anti-inflammatory miR-146a, a decrease in the level of expression of pro-inflammatory miR-155 which may signify the strengthening of antiviral control. The study data demonstrated the decrease in the expression of miR EBV (BART-13 and BART-15) and TLR9 on the immunocompetent cells that can also be attributed to the criteria for IP effectiveness. The effectiveness of IP was also proved by the stabilization of cell mechanisms, namely the tendency to normalizing T and B cell populations, decrease in the number of natural killer cells and activated cells (CD25+, CD3+ HLA DR+). On the other hand, the number of lymphocytes with suppressor activity (CD4+25+) remained significantly high mitigating autoimmune aggression. The results of the study show that the use of IP for treating the acute phase of EBV infection contributed to the decrease of repliсative activity of the virus; suppressing the aggressiveness of autoimmune reactions. The decrease in the expression of miR EBV (BART-13 and BART-15) can be recommended as a criterion for the IP effectiveness; the decrease in the expression of TLR9 on immunocompetent cells –as a criterion for suppressing autoimmune reactions.
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