Immune inflammation, cellular and humoral immunity in patients with early development of coronary heart disease

O. Lomakovsky
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Abstract

The aim – to identify a possible relationship between the early development of coronary artery disease and the level of cellular and humoral indicators of adaptive and innate immunity, immune inflammation in order to clarify the effect of the immune system on the early development of atherosclerosis.Materials and methods. IHD patients with stable angina pectoris were divided into two groups: the first group (n=112) included patients with the development of clinical manifestations of IHD after 60 years (65.7±4.3 years), the second group (n=108) – patients with the development of clinical manifestations of coronary artery disease before 45 years (43.7±4.8 years). The material for the immunological study was peripheral venous blood. To determine the parameters of cellular and humoral innate and adaptive immunity in blood serum and supernatants of mononuclear cells, enzyme immunoassay was used.Results and discussion. Comparative characteristics of patients with the development of clinical manifestations of ischemic heart disease up to 45 years compared with patients with their development after 60 years showed: clinical manifestations of dynamic coronary stenosis – in 33 versus 14 % of patients (p=0.046) (R=–0.21; p=0.046), the presence of heredity of ischemic heart disease – in 45 versus 15 % of patients (p=0.030) (R=–0.31; p=0.029), the level of specific antibodies to the damaged aorta is 10 (10–20) versus 5 (0–10) cu (р=0.033) (R=–0.31; p=0.01), the number of activated B cells with a CD40 index was 9.5 (7.0–11.9) versus 7.1 (5.6–9.9) % (p=0.019) (R=–0.32; p=0.018), free radical oxidation of proteins – 5.2 (4.0–6.6) versus 4.2 (1.7–5.7) cu (p=0.006) (R=–0.19; p=0.005), stable metabolite of blood nitric oxide NO2 – 0.95 (0.58–1.06) and 1.04 (0.70–1.54) mg/ml (p=0.036) (R=0.17; p=0.036), IL-2 in mononuclear cells – 18.7 (15.5–21.3) versus 14.5 (11.4–15.7) pg/ml (p=0.019) (R=–0.43; p=0.016). According to factor analysis, the main independent variables were identified: IL-6 (factor 1), functional and metabolic activity of monocytes (factor 2), antibodies to arterial components (factor 3) and CRP (factor 4). Analysis of multivariate linear regression showed the total relationship of the studied factors with the early development of clinical manifestations of coronary artery disease (R=0.30; F=2.5; p=0.048) with the dominant influence of inflammatory CRP (B=0.19; p=0.046) and activity monocytes (B=0.20; p=0.045). A step-by-step analysis of linear regression found a total relationship between the early development of IHD (R=0.41; F=3.7; p=0.017) with CRP (B=0.21; p=0.10), monocyte activity (B=0.22; p=0.08) and antibodies to arterial components (B=0.21; p=0.11).Conclusions. The early development of clinical manifestations of coronary artery disease (up to 45 years) compared with their development after 60 years is associated with a high level of activated B-lymphocytes and antibodies to the tissues of the vascular wall, active synthesis of pro-inflammatory IL-2, and a low level of anti-inflammatory IL-10. A simultaneous increase in the level of CRP, antibodies to arterial components and functional and metabolic activity of monocytes is directly related to the early development of clinical manifestations of coronary artery disease. The early development of ischemic heart disease is accompanied by the presence of heredity of ischemic heart disease, high activity of free-radical oxidation of proteins and expressive impairment of endothelial function.
冠心病早期发展患者的免疫炎症、细胞和体液免疫
目的-确定冠状动脉疾病早期发展与适应性和先天免疫、免疫炎症的细胞和体液指标水平之间的可能关系,以阐明免疫系统对动脉粥样硬化早期发展的影响。材料和方法。将IHD合并稳定型心绞痛患者分为两组:第一组(n=112)为60年后出现IHD临床表现的患者(65.7±4.3年),第二组(n=108)为45年前出现冠状动脉疾病临床表现的患者(43.7±4.8年)。免疫学研究的材料是外周静脉血。采用酶免疫分析法测定单核细胞血清和上清液的细胞和体液固有免疫和适应性免疫参数。结果和讨论。出现缺血性心脏病临床表现的45岁以下患者与60岁后出现缺血性心脏病临床表现的患者的比较特征显示:33%的患者表现为动态冠状动脉狭窄,14%的患者表现为动态冠状动脉狭窄(p=0.046) (R= - 0.21;p=0.046),缺血性心脏病的遗传存在- 45%对15%的患者(p=0.030) (R= - 0.31;p=0.029),受损主动脉特异性抗体水平为10(10 - 20)比5 (0-10)cu (R= -0.31;p=0.01), CD40指数激活的B细胞数为9.5% (7.0 ~ 11.9)vs 7.1 (5.6 ~ 9.9) % (p=0.019) (R= -0.32;p=0.018),自由基氧化蛋白质- 5.2(4.0-6.6)对4.2 (1.7-5.7)cu (p=0.006) (R= - 0.19;p=0.005),血液一氧化氮NO2稳定代谢物- 0.95(0.58-1.06)和1.04 (0.70-1.54)mg/ml (p=0.036) (R=0.17;p=0.036),单核细胞IL-2分别为18.7(15.5-21.3)和14.5 (11.4-15.7)pg/ml (p=0.019) (R= - 0.43;p = 0.016)。根据因子分析,确定了主要的自变量:IL-6(因子1)、单核细胞功能和代谢活性(因子2)、动脉成分抗体(因子3)和CRP(因子4)。多元线性回归分析显示,所研究的因素与冠状动脉疾病早期临床表现的总相关关系(R=0.30;F = 2.5;p=0.048),炎性CRP占主导地位(B=0.19;p=0.046)和活性单核细胞(B=0.20;p = 0.045)。逐步的线性回归分析发现,IHD早期发展之间的总体关系(R=0.41;F = 3.7;p=0.017)与CRP (B=0.21;p=0.10),单核细胞活性(B=0.22;p=0.08)和动脉成分抗体(B=0.21;.Conclusions p = 0.11)。冠状动脉疾病临床表现的早期发展(长达45年)与60年后的发展相比,与高水平的活化b淋巴细胞和血管壁组织抗体、促炎IL-2的活跃合成和低水平的抗炎IL-10有关。CRP、动脉成分抗体及单核细胞功能代谢活性同时升高与冠状动脉疾病临床表现的早期发展有直接关系。缺血性心脏病的早期发展伴随着缺血性心脏病的遗传、蛋白质自由基氧化的高活性和内皮功能的表达性损伤。
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