多肌炎/皮肌炎患者血清PAD4水平及其与中性粒细胞胞外诱捕网的相关性

Levels of Serum PAD4 in Patients with Polymyositis/Dermatomyositis and Its Correlation with NET

目的观察多肌炎/皮肌炎(polymyositis/dermatomyositis,PM/DM)患者血清肽基精氨酸脱亚胺酶4(peptidyl arginine deiminase 4,PAD4)水平及其与血清中性粒细胞胞外诱捕网(neutrophil extracellular trap,NET)标志物水平和其他临床指标的相关性。方法收集60例PM/DM患者(DM 36例、PM 24例)和20例健康对照者的外周血,检测其血清中PAD4及NET标志物[瓜氨酸化组蛋白H3(citrullinated histone H3,CitH3)及细胞游离DNA(cell free DNA,cfDNA)]水平,分析其相关性,并与患者临床资料进行相关性分析。结果与健康对照者比较,PM/DM患者血清中PAD4水平显著升高(t=13.21,P<0.001)。PM/DM患者血清NET标志物水平相比健康对照者显著升高(CitH3:t=9.518,P<0.001;cfDNA:t=2.984,P=0.0038)。将PM/DM患者PAD4与NET标志物水平进行相关性分析,结果显示,两者均呈正相关(PAD4与CitH3:r=0.835,P<0.001;PAD4与cfDNA:r=0.322,P=0.012)。将PM/DM患者血清PAD4、CitH3、cfDNA水平与临床数据做相关性分析,结果显示,血清PAD4水平与红细胞沉降率(erythrocyte sedimentation rate,ESR)、降钙素原(procalcitonin,PCT)呈正相关,与白蛋白(albumin,ALB)水平呈负相关;血清CitH3水平与谷丙转氨酶(alanine aminotransferase,ALT)呈正相关;血清cfDNA水平与白细胞计数(white blood cell count,WBC)、中性粒细胞绝对值(neutrophil,NE#)、中性粒细胞百分比(neutrophil ratio,NE%)、C反应蛋白(C-reactive protein,CRP)、白细胞介素-6(interleukin-6,IL-6)、ALT、谷草转氨酶(aspartate aminotransferase,AST)、肌酸激酶(creatine kinase,CK)、乳酸脱氢酶(lactate dehydrogenase,LDH)、尿素(UREA)等指标均呈正相关,与ALB水平呈负相关。结论PM/DM患者血清PAD4水平显著升高并且与NET异常增多有关,同时,血清PAD4及NET标志物水平与PM/DM患者炎性指标呈正相关,提示PAD4异常增多介导NET过度形成可能参与PM/DM的发病。

Objective To observe the level of serum peptidyl arginine deiminase 4(PAD4)in patients with polymyositis/dermatomyositis(PM/DM)and its correlation with serum neutrophil extracellular traps(NET)markers and other clinical indicators.Methods The peripheral blood of 60 patients with PM/DM(36 cases of DM,24 cases of PM)and 20healthy controls were collected.The levels of PAD4 and NET markers[citrullinated histone H3(CitH3)and cell free DNA(cfDNA)]in serum were detected,the correlation between them was analyzed,and their correlation with clinical data were also analyzed.Results Compared with healthy controls,the level of serum PAD4 in PM/DM patients was significantly increased(t=13.21,P<0.001).The level of serum NET markers in PM/DM patients was significantly higher than that in healthy controls(CitH3:t=9.518,P<0.001;cfDNA:t=2.984,P=0.0038).The correlation analysis between serum PAD4 and NET marker levels in PM/DM patients showed that there was a positive correlation(PAD4 and CitH3:r=0.835,P<0.001;PAD4 and cfDNA:r=0.322,P=0.012).The correlation analysis of serum PAD4,CitH3 and cfDNA levels with clinical data showed that PAD4 levels were positively correlated with erythrocyte sedimentation rate(ESR)and procalcitonin(PCT),and negatively correlated with albumin(ALB)levels.There was a positive correlation between serum CitH3 level and alanine aminotransferase(ALT).Serum cfDNA level was positively correlated with white blood cell(WBC),neutrophil(NE#),neutrophil ratio(NE%),C-reactive protein(CRP),interleukin-6(IL-6),ALT,aspartate aminotransferase(AST),creatine kinase(CK),lactate dehydrogenase(LDH)and UREA,and negatively correlated with ALB level.Conclusion Serum PAD4 levels in PM/DM patients were significantly increased and correlated with abnormal increase of NET.Meanwhile,PAD4 and NET marker levels in serum were positively correlated with inflammatory markers of PM/DM patients,suggesting that abnormal increase of PAD4mediated excessive formation of NET may be involved in the pathogenesis of PM/DM.