Objective: To investigate the expression of CD(55) and myeloperoxidase (MPO) on neutrophils in patients with MPO-specific anti-neutrophil cytoplasmic antibody associated vasculitis(MPO-AAV), and analyze the relationship between the expression and clinical manifestation. Methods: Forty untreated patients with active MPO-AAV (patient group) and 30 healthy volunteers (control group) were enrolled in this study. The CD(55) on neutrophils and both membrane and cytoplasmic MPO were detected by flow cytometry. Serum fragment-from the activated complement factor B(Ba) and MPO were measured by ELISA. The clinical activity of vasculitis was valued by Birmingham vasculitis activity score-version 3(BVAS-V3). The significance of laboratory data was evaluated by Spearman correlation test and multivariate linear regression analysis. Results: (1)The mean fluorescence intensity(MFI) of CD(55) expressed on neutrophils was significantly higher than that in control group[4 068.6±2 306.0 vs 2 999.5±1 504.9, P=0.033]. Similar results of serum MPO and Ba in patient group were found compared to controls [500.0(381.0, 612.7) IU/L vs 286.9(225.5, 329.1) IU/L, P<0.001; 35.2(25.2, 79.5) ng/L vs 18.0(15.0, 28.0) ng/L, P<0.001], respectively. However, MIF of cytoplasmic MPO in patients was significantly lower than that of control group(1 577.1±1 175.9 vs 3 105.3±2 323.0, P=0.003) . (2) In patient group, cytoplasmic intensity of MPO was negatively associated with the serum levels of MPO(r=-0.710, P<0.001) and Ba (r=-0.589, P=0.001). Moreover, serum MPO was positively associated with serum Ba(r=0.691, P<0.001). Membrane intensity of CD(55) on neutrophils was positively correlated with patient age (r=0.514, P=0.001), C reactive protein (r=0.376, P=0.018), peripheral neutrophils count (r=0.485, P=0.001) and BVAS-V3 (r=0.484, P=0.002), whereas negative correlation between membrane CD(55) and disease duration was seen (r=-0.403, P=0.01). (3) The result of multiple linear regression analysis showed there was statistically significant positive correlation between MFI of CD(55) expressed on neutrophils and BVAS-V3 (β=0.001, P=0.027). Conclusions: In MPO-AAV, CD(55) expression on neutrophils is markedly enhanced, which is one of the independent risk factors related to disease activity. It might protect neutrophils from attacking AAV, CD(55) expression on neutrophils is markedly enhanced, which is one of the independent risk factors related to disease activity. It might protect neutrophils from attacking by complement alternative pathway. Activated neutrophils release more MPO and lysosome to intensify the inflammation reaction and aggravate the disease. Thus CD(55) might become a new potential target for the treatment of this disease in the future.
目的： 初步探讨髓过氧化物酶(MPO)-抗中性粒细胞胞质抗体(ANCA)相关性血管炎(AAV)患者外周血中性粒细胞CD(55)、MPO表达及其意义。 方法： 选40例初诊活动期MPO-AAV患者为血管炎组，30例健康志愿者为健康对照组，采用流式细胞术检测2组受试者外周血中性粒细胞CD(55)和MPO表达水平，ELISA检测外周血MPO和补体B因子活化片段a(Ba)水平，评估患者伯明翰血管炎活动度评分(BVAS-V3)，采用Spearman相关分析和多元线性回归分析指标间的关系。 结果： (1)血管炎组患者外周血中性粒细胞膜CD(55)表达(4 068.6±2 306.0比2 999.5±1 504.9，P＝0.033)、血清MPO[500.0(381.0, 612.7) IU/L比286.9(225.5, 329.1) IU/L，P<0.001]和Ba[35.2(25.2, 79.5) ng/L比18.0(15.0, 28.0) ng/L，P<0.001]水平均高于健康对照组。血管炎组患者中性粒细胞胞内MPO表达水平低于健康对照组(1 577.1±1 175.9比3 105.3±2 323.0，P＝0.003)。(2)血管炎组患者中性粒细胞胞内MPO表达水平分别与外周血MPO水平(r＝－0.710，P<0.05)和Ba水平(r＝－0.598，P<0.05)呈负相关；血清MPO与Ba水平呈正相关(r＝0.691，P<0.05)；中性粒细胞CD(55)表达分别与患者年龄(r＝0.514, P＝0.001)、C反应蛋白(r＝0.376，P＝0.018)、中性粒细胞计数(r＝0.485, P＝0.001)及BVAS-V3(r＝0.484, P＝0.002)呈正相关，与病程呈负相关(r＝－0.403，P＝0.01)。(3)多元线性回归分析显示，中性粒细胞CD(55)表达与BVAS-V3呈正相关(β＝0.001，P＝0.027)。 结论： CD(55)在MPO-AAV患者中性粒细胞膜表达增强，且是影响病情活动的独立危险因素，其可能通过保护细胞免受激活补体旁路的破坏促进炎症反应，加重病情。CD(55)可能是治疗MPO-AAV未来的潜在的新靶点。.
Keywords: Anti-myeloperoxidase antibody; Antibodies, antineutrophil cytoplasmic; CD(55); Vasculitis.