Liu Y, Peng X C, Xu J N, Zheng M J, Shuai Z W
Department of Rheumatology and Immunology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Department of Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Zhonghua Nei Ke Za Zhi. 2022 Sep 1;61(9):1016-1022. doi: 10.3760/cma.j.cn112138-20210914-00638.
To investigate the expression and clinical significance of neutrophil myeloperoxidase (MPO) in patients with MPO-antibody associated vasculitis (AAV). Thirty-six newly diagnosed MPO-AAV patients who were hospitalized in the First Affiliated Hospital, Anhui Medical University from July 2018 to June 2021 were enrolled,and 36 age and sex matched healthy subjects were selected as controls. Neutrophil MPO level was detected by flow cytometry (FCM) and MPO mRNA was tested by real time quantitative polymerase chain reaction (RT-qPCR) in all subjects. Serum complement fragment C5 (C5a) and MPO in both groups and serum MPO-anti-antineutrophilic cytoplasmic antibody(ANCA) in MPO-AAV group were measured by enzyme linked immunosorbent assay (ELISA), while the disease activity was evaluated by Birmingham vasculitis activity score-V3 (BVAS-V3). Compared with the heathy control group, the expression of MPO mRNA in neutrophils, serum MPO and complement C5a in MPO-AAV group were significantly higher[MPO mRNA:30.2±11.5 vs. 1.9±0.6, <0.001;MPO:(112.0±68.7) IU/L vs. (87.4±22.9) IU/L, =0.01; C5a:(187.3±90.3) ng/ml vs. (107.3±31.1) ng/ml, <0.001; respectively], while the mean fluorescence intensity (MFI) of MPO in neutrophils were significantly lower [ 1 343.3±723.4 vs. 2 868.0±1 136.5, <0.001]. In MPO-AAV group, the expression of neutrophil MPO mRNA was positively correlated with serum MPO-ANCA and MPO levels (=0.537, =0.001 and =0.358, =0.032; respectively). Multiple regression analysis suggested that neutrophil MPO mRNA expression was positively correlated with serum MPO-ANCA level (=0.695, =0.006); neutrophil MPO level was negatively correlated with serum MPO-ANCA, MPO and complement C5a levels (=-0.335, =0.046; =-0.372, =0.026; =-0.577, <0.001; respectively). Further, neutrophil MPO level was negatively correlated with serum complement C5a level (=-0.374, =0.043). BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils, serum MPO-ANCA, MPO and complement C5a (=0.598, <0.001; =0.599, <0.001; =0.537, =0.001; =0.415, =0.012; respectively) and negatively correlated with MPO level in neutrophils (=-0.342, =0.041). In multiple regression analysis it suggested that BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils (=0.511, =0.002). In MPO-AAV patients, MPO synthesis and release in neutrophils are both significantly increased, which might be influenced by serum MPO-ANCA and C5a, respectively. Furthermore, MPO synthesis activity in neutrophils is an independent factor related to disease activity.
探讨中性粒细胞髓过氧化物酶（MPO）在MPO抗体相关血管炎（AAV）患者中的表达及临床意义。选取2018年7月至2021年6月在安徽医科大学第一附属医院住院的36例新诊断的MPO-AAV患者，并选取36例年龄和性别匹配的健康受试者作为对照。采用流式细胞术（FCM）检测所有受试者中性粒细胞MPO水平，采用实时定量聚合酶链反应（RT-qPCR）检测MPO mRNA。采用酶联免疫吸附测定（ELISA）检测两组患者血清补体片段C5（C5a）和MPO以及MPO-AAV组患者血清MPO抗中性粒细胞胞浆抗体（ANCA），同时采用伯明翰血管炎活动评分-V3（BVAS-V3）评估疾病活动度。与健康对照组相比，MPO-AAV组中性粒细胞MPO mRNA表达、血清MPO和补体C5a显著升高[MPO mRNA：30.2±11.5 vs. 1.9±0.6，<0.001；MPO：（112.0±68.7）IU/L vs.（87.4±22.9）IU/L，=0.01；C5a：（187.3±90.3）ng/ml vs.（107.3±31.1）ng/ml，<0.001]，而中性粒细胞MPO平均荧光强度（MFI）显著降低[1343.3±723.4 vs. 2868.0±1136.5，<0.001]。在MPO-AAV组中，中性粒细胞MPO mRNA表达与血清MPO-ANCA和MPO水平呈正相关（分别为=0.537，=0.001和=0.358，=0.032）。多元回归分析表明，中性粒细胞MPO mRNA表达与血清MPO-ANCA水平呈正相关（=0.695，=0.006）；中性粒细胞MPO水平与血清MPO-ANCA、MPO和补体C5a水平呈负相关（分别为=-0.335, =0.046；=-0.372, =0.026；=-0.577, <0.001）。此外，中性粒细胞MPO水平与血清补体C5a水平呈负相关（=-0.374, =0.043）。BVAS-V3与中性粒细胞MPO mRNA表达、血清MPO-ANCA、MPO和补体C5a呈正相关（分别为=0.598, <0.001；=0.599, <0.001；=0.537, =0.001；=0.415, =0.012），与中性粒细胞MPO水平呈负相关（=-0.342, =0.041）。多元回归分析表明，BVAS-V3与中性粒细胞MPO mRNA表达呈正相关（=0.511, =0.002）。在MPO-AAV患者中，中性粒细胞中MPO的合成和释放均显著增加，这可能分别受血清MPO-ANCA和C5a的影响。此外，中性粒细胞中MPO的合成活性是与疾病活动度相关的独立因素。
