MPO-ANCA相关性血管炎中性粒细胞CD35、CD55、MPO表达以及外周血、尿Ba水平的变化及意义

发布时间：2018-11-09 14:22

【摘要】：背景MPO-ANCA相关性血管炎(myeloperoxidase-specific antineutrophil cytoplasmic autoantibody associated vasculitis,MPO-AAV)是我国最常见的小血管炎类型之一,可表现为显微镜下多血管炎(Microscopic polyangiitis,MPA)、肉芽肿性多血管炎(Granulomatosis with polyangiitis,GPA)及嗜酸性肉芽肿性多血管炎(Eosinophilic granulomatosis with polyangiitis,EGPA)。由于这类疾病发病较隐匿、临床表现多样、进展快,患者常因未及时诊治而导致病情延误甚至死亡。近年来,研究者们通过动物实验、体外实验和临床研究发现补体旁路途径的激活在MPO-AAV的发病及病情进展中可能起到了重要作用。补体系统的激活受到多种因素调控,如CD35、CD55。有研究报道显示CD35、CD55在类风湿关节炎(rheumatoid arthritis,RA)等自身免疫病中,对补体系统的调节起到了重要作用,而在MPO-AAV中,其与补体激活之间的关系尚未见研究报道。目的探讨MPO-AAV患者中性粒细胞活性、补体旁路激活及调节剂水平的变化及其与临床损害间的关系。方法收集40例活动性MPO-AAV患者的全血、血清及尿液,并记录患者的临床损害情况及伯明翰血管炎活动度积分(Birmingham Vasculitis Activity Score-version3,BVAS-V3)。另收集30例健康人全血、血清及尿液作为正常对照组。运用流式细胞术(flow cytometry,FCM)分析MPO-ANCA阳性的患者和健康人外周血中性粒细胞CD35、CD55及MPO的表达,同时运用酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)方法对患者和健康人血清及尿液中Ba水平进行检测,并探讨CD35、CD55、MPO、Ba的水平与患者临床损害间的关系。结果1.MPO-AAV患者组中性粒细胞CD35、CD55的表达水平均高于正常对照组(t=3.339,p=0.001;t=2.180,p=0.033)。MPO-AAV患者组MPO细胞内表达水平低于正常对照组(t=-3.161,p=0.003);MPO-AAV患者组血清Ba浓度较对照组高(Z=-4.641,p0.001);2.MPO-AAV患者中性粒细胞CD35的平均荧光强度与血清Ba、尿液Ba呈正相关(r=0.336,p=0.034;r=0.324,p=0.041)。3.MPO-AAV患者中性粒细胞CD35的平均荧光强度与患者年龄(r=0.424,p=0.006)、C反应蛋白(r=0.516,p=0.001)、补体C3(r=0.494,p=0.020)、外周血中性粒细胞计数(r=0.415,p=0.008)呈正相关;CD55的平均荧光强度与患者年龄(r=0.514,p=0.001)、总BVAS(r=0.441,p=0.004)、CRP(r=0.377,p=0.020)、补体C4(r=0.445,p=0.038)、外周血中性粒细胞计数(r=0.485,p=0.001)、胸部损害BVAS(r=0.358,p=0.023)呈正相关;MPO细胞内表达的平均荧光强度与补体C4呈正相关(r=0.572,p=0.021);血清Ba浓度与患者病程呈负相关(r=-0.323,p=0.042);尿液中Ba与患者ESR(r=0.373,p=0.025)、CRP(r=0.399,p=0.013)、胸部BVAS(r=0.318,p=0.046)呈正相关。4.MPO-AAV患者中,有肺损害患者较无肺损害患者CD35和MPO的平均荧光强度更高(t=-2.373,p=0.023;t=-2.121,p=0.043);有肾损害患者较无肾损害患者CD55的MFI更高(t=-2.412,p=0.021)。结论1.补体激活抑制因子CD35、CD55在MPO-AAV患者中性粒细胞的表达是显著增强的,可能减少中性粒细胞被激活的补体系统破坏,加重中性粒细胞参与的炎症反应。2.中性粒细胞CD35高表达的MPO-AAV患者肺脏可能更易受到累及;CD55高表达者肾脏可能更易受到累及。3.MPO-AAV患者中性粒细胞内MPO的表达水平明显降低,提示中性粒细胞脱颗粒中的MPO可能在MPO-AAV病情发生和发展中发挥更加重要的作用。4.MPO-AAV患者补体旁路激活明显增加,但周围血中Ba的升高水平与患者临床损害严重性间无显著相关性,患者尿中Ba水平的检测,可能用于协助判断MPO-AAV病情活动性。
[Abstract]:Background MPO-ANCA-associated vascular inflammation (MPO-AAV) is one of the most common types of vasculitis in our country. It can be seen as a microscopic polyangitis (MPA), a granulomatous polyangitis (GPA) and an eosinophilic granuloma with polyangitis. EGPA). Because the disease of this kind of disease is more insidious, the clinical manifestations are various, the progress is fast, the patient often causes the disease to delay or even death due to the failure of timely diagnosis and treatment. In recent years, by animal experiments, in vitro experiments and clinical studies, the activation of the complement bypass pathway may play an important role in the pathogenesis of MPO-AAV and the progression of the disease. Activation of the complement system is regulated by a variety of factors, such as CD35, CD55. It is reported that CD35 and CD55 play an important role in the regulation of complement system in autoimmune diseases such as rheumatoid arthritis (RA), and the relationship between the complement activation in MPO-AAV has not been reported. Objective To study the changes of neutrophil activity, complement bypass activation and regulator level in patients with MPO-AAV and their relationship with clinical damage. Methods The whole blood, serum and urine of 40 patients with active MPO-AAV were collected and the clinical damage and the activity score of Birmingham Vasculitis Activity Score-version3, BVAS-V3 were recorded. The whole blood, serum and urine of 30 healthy people were collected as the normal control group. The expression of CD35, CD55 and MPO in peripheral blood of patients with MPO-ANCA positive and the expression of CD35, CD55 and MPO were analyzed by flow cytometry (FCM), and the levels of Ba in serum and urine of patients and healthy people were detected by enzyme-linked immunosorbent assay (ELISA), and CD35 was also discussed. The relationship between the level of CD55, MPO and Ba and the clinical damage of the patient. Results The expression of CD35 and CD55 in the patients with MPO-AAV was higher than that in the normal control group (t = 3.339, p = 0.001; t = 2.180, p = 0.033). The expression of MPO in the MPO-AAV group was lower than that in the control group (t =-3.161, p = 0.003); the serum Ba concentration in the MPO-AAV group was higher than that in the control group (Z =-4.641, p0.001); 2. The average fluorescence intensity of the neutrophils CD35 in the MPO-AAV group was positively correlated with the serum Ba and the urine Ba (r = 0.336, p = 0.034; r = 0.324, The mean fluorescence intensity of the C-reactive protein (r = 0. 516, p = 0. 001), the C-reactive protein (r = 0. 516, p = 0. 001), the complement C3 (r = 0.494, p = 0. 020), the peripheral blood neutrophil count (r = 0.415, p = 0. 008) was positively correlated with the patient's age (r = 0.415, p = 0. 008), and the mean fluorescence intensity of the CD55 was related to the patient's age (r = 0.514, p = 0.001), and the total BVAS (r = 0.441, p = 0. 004), CRP (r = 0.377, p = 0. 020), complement C4 (r = 0.445, p = 0.038), peripheral blood neutrophil count (r = 0.485, p = 0.001), chest damage BVAS (r = 0.358, p = 0.023), and positive correlation between the average fluorescence intensity and complement C4 in MPO cells (r = 0.572, p = 0.021); the serum Ba concentration was negatively correlated with the course of the patient (r =-0.323, In urine, Ba was positively correlated with ESR (r = 0.373, p = 0.025), CRP (r = 0.399, p = 0.013), breast BVAS (r = 0.318, p = 0.046), and the mean fluorescence intensity of CD35 and MPO in patients with lung damage in patients with lung impairment was higher in patients with lung impairment (t =-2.373, p = 0.023; t =-2.121, p = 0.043); The MFI of CD55 in patients with renal impairment was higher in patients with no renal impairment (t =-2.412, p = 0.021). Conclusion 1. The expression of the complement activation inhibitor CD35, CD55 in the MPO-AAV patient is significantly enhanced, and it is possible to reduce the complement system that is activated by the neutrophils and to aggravate the inflammatory response of the neutrophils. Neutrophil CD35 high-expressed MPO-AAV patient lung may be more susceptible to involvement; the CD55 high-expression kidney may be more susceptible to involvement. 3. The level of expression of MPO in the neutrophils of the MPO-AAV patient is significantly reduced, It was suggested that MPO might play a more important role in the pathogenesis and development of MPO-AAV. It may be used to assist in the determination of MPO-AAV disease activity.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R543

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