Characteristic changes of extracellular Dna levels, indices of netosis and inflammation in peripheral blood in patients with asthma

Elena D. Gavrilova, E. V. Goiman, E. N. Demchenko, D. V. Demina, N. N. Volskiy, V. A. Kozlov
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Abstract

Many studies have shown that the level of cell-free DNA (cfDNA) in blood of patients with oncological diseases, sepsis, systemic lupus erythematosus, and some rheumatic diseases significantly exceeds the value of similar index in healthy donors and is closely related to the clinical features of the disease. Systemic inflammatory response is among the most frequent pathophysiological processes along with markedly changed levels of cfDNA in blood plasma. The levels of cfDNA in blood plasma of patients with RA are shown to be closely associated with a shifted balance of helpers to the Th1-side. It is an adequate intensity index of inflammatory processes and effectiveness of therapy. At the same time, there only limited number of works concerning changes in cfDNA levels in pathological processes with predominance of Th2 lymphocytes. According to generally accepted concept, the pathogenesis of bronchial asthma is of distinct interest, being critically dependent on the production of specific antibodies controlled by activated Th2 lymphocytes. The aim of this work was to study the level of cfDNA in blood and compare its changes with intensity of NETs and inflammation in patients with asthma. The study included 20 patients with asthma, who underwent hospital treatment at the Department Allergology (Clinic of Immunopathology, RIFCI, Novosibirsk), and 10 conditionally healthy donors. We have shown that, upon admission to the clinic, the level of cfDNA in patients with asthma was significantly reduced against the control group of healthy donors. After a course of therapy, the average level of cfDNA in patients plasma was increased and did not differ statistically significantly from this index in controls. The data obtained for other parameters indicate that the patients with asthma did not reveal any signs of pronounced systemic inflammatory response. One should suggest that the observed changes in the level of cfDNA in blood plasma in bronchial asthma are not caused by chronic inflammatory process in lungs of these patients, but they are determined by some other pathophysiological mechanisms. It has been shown that the level of in vitro stimulated NETs in patients with asthma is higher than in healthy donors, thus being consistent with current opinions on the role of neutrophils in pathogenesis of asthma.
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哮喘患者外周血细胞外Dna水平、坏死及炎症指标的特征性变化
许多研究表明,肿瘤疾病、脓毒症、系统性红斑狼疮和一些风湿性疾病患者血液中的游离DNA (cfDNA)水平明显超过健康献血者的类似指标值,与疾病的临床特征密切相关。全身炎症反应是最常见的病理生理过程之一,伴随着血浆中cfDNA水平的显著改变。类风湿性关节炎患者血浆中cfDNA的水平与辅助物向th1侧转移的平衡密切相关。它是炎症过程和治疗有效性的适当强度指标。同时,关于以Th2淋巴细胞为主的病理过程中cfDNA水平变化的研究较少。根据普遍接受的概念,支气管哮喘的发病机制具有独特的意义,它严重依赖于由活化的Th2淋巴细胞控制的特异性抗体的产生。这项工作的目的是研究血液中cfDNA的水平,并比较其变化与哮喘患者NETs和炎症的强度。该研究包括20名在过敏科(新西伯利亚RIFCI免疫病理诊所)接受住院治疗的哮喘患者和10名有条件的健康供体。我们已经证明,在进入诊所时,哮喘患者的cfDNA水平与健康供体对照组相比显着降低。治疗一个疗程后,患者血浆中cfDNA平均水平升高,与对照组相比无统计学差异。其他参数的数据表明哮喘患者没有显示出任何明显的全身炎症反应的迹象。提示支气管哮喘患者血浆cfDNA水平的变化并非由肺部慢性炎症过程引起,而是由其他病理生理机制决定的。研究表明,哮喘患者体外刺激的NETs水平高于健康供者,这与目前关于中性粒细胞在哮喘发病机制中的作用的观点一致。
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