Professor, Department of Internal Diseases with a Course of Cardiology and Functional Diagnostics named after Academician V.S. Moiseev; Peoples' Friendship University of Russia, 6 Miklukho-Maklaya St., Moscow, 117198, Russia.
Senior Researcher, Research Laboratory; Moscow Regional Research Clinical Institute named after M.F. Vladimirsky, 61/2-1 Schepkina St., Moscow, 129110, Russia.
Sovrem Tekhnologii Med. 2021;13(3):47-53. doi: 10.17691/stm2021.13.3.06. Epub 2021 Jun 28.
was to determine the molecular genetic prognostic criteria for the severity of the course pneumonia based on the analysis of the association of genetic polymorphism in toll-like receptors with the severity of NETosis.
The study included 38 patients with the main diagnosis of community-acquired pneumonia with a severe course. All the patients underwent standard clinical laboratory examinations, computed tomography of the thoracic organs, microbiological examination of blood and tracheobronchial aspirate. The level of neutrophilic extracellular traps (NETs) in blood smears was determined on the 1-2 and 5-7 days of hospitalization. Genotyping of rs5743551 (), rs5743708 (), and rs4986790 () polymorphic loci was performed by pyrosequencing.
The level of NETs on the 1 day of admission was statistically significantly lower in heterozygous and homozygous carriers of rs4986790 () polymorphism (AG and GG genotypes) compared with patients with the wild-type genotype (AA genotype) (p<0.05). When comparing the number of NETs with genotypes for rs5743708 () and rs5743551 () polymorphisms, no statistically significant correlation was found (p>0.05). The study of the NET level in dynamics demonstrated a decrease in the NETosis activity of neutrophils during the first week of hospitalization (p<0.05). The presence of the G allele in the patient's genotype for rs5743551 () polymorphism increases the risk of a poor outcome of the disease (p<0.0001) (OR=20.3; 95% CI (4.3-135.0)).
The obtained data suggest that level of NETs is a marker of the activity of neutrophils which are closely related to the studied genetic polymorphisms, and affects the prognosis of the pneumonia outcome.
通过分析 toll 样受体基因多态性与中性粒细胞胞外诱捕网（NETosis）严重程度的相关性，确定肺炎严重程度的分子遗传预后标准。
本研究纳入了 38 例主要诊断为重症社区获得性肺炎的患者。所有患者均接受了标准的临床实验室检查、胸部器官计算机断层扫描、血液和支气管抽吸物的微生物检查。在入院第 1-2 天和第 5-7 天，测定血涂片中性粒细胞胞外陷阱（NETs）的水平。通过焦磷酸测序法对 rs5743551()、rs5743708()和 rs4986790()多态性位点进行基因分型。
入院第 1 天，与野生型基因型（AA 基因型）相比，rs4986790()多态性（AG 和 GG 基因型）杂合和纯合携带者的 NETs 水平统计学显著降低（p<0.05）。比较 rs5743708()和 rs5743551()多态性的基因型与 NET 数量，未发现统计学显著相关性（p>0.05）。动态研究 NET 水平表明，住院第 1 周期间，中性粒细胞 NETosis 活性降低（p<0.05）。患者 rs5743551()多态性的基因型中 G 等位基因的存在增加了疾病不良结局的风险（p<0.0001）（OR=20.3；95%CI（4.3-135.0））。
所得数据表明，NETs 水平是与研究的遗传多态性密切相关的中性粒细胞活性的标志物，并且影响肺炎结局的预后。
