糖萼组分在不同类型抗中性粒细胞胞浆抗体相关性血管炎中的变化及其与疾病活动度的关系

Changes of glycocalyx fractions in different types of anti-neutrophil cytoplasmic antibody-associated vasculitis and their correlation with disease activity

目的 探讨糖萼组分在不同类型抗中性粒细胞胞浆抗体(ANCA)相关性血管炎(AAV)中的变化及其与疾病活动度的关系。方法 纳入49例AAV患者(AAV组)和53例健康者(对照组)。采用PCR仪辅助酸降解法和高效液相色谱检测两组受试者6种血清降解单糖水平。比较AAV组和对照组受试者、肉芽肿性多血管炎(GPA)和显微镜下多血管炎(MPA)患者、髓过氧化物酶(MPO)-ANCA和蛋白酶3(PR3)-ANCA阳性AAV患者、非活动、活动和高度活动AAV患者血清降解单糖水平。采用Spearman相关分析评估AAV患者血清降解单糖水平与各临床指标的相关性。采用受试者工作特征(ROC)曲线评价血清降解半乳糖胺(GalN_de)水平对MPO-ANCA阳性AAV疾病高度活动的预测价值。结果 AAV组受试者血清降解岩藻糖(Fuc_de)、GalN_de、降解葡萄糖(Glc_de)、降解甘露糖(Man_de)、总血清降解单糖水平均高于对照组(P<0.05)。MPA患者总血清降解单糖水平高于GPA患者(P<0.05)。MPO-ANCA阳性AAV患者总血清降解单糖水平高于PR3-ANCA阳性AAV患者(P<0.05)。非活动、活动及高度活动AAV患者血清GalN_de水平比较差异有统计学意义,其中高度活动患者高于非活动患者(P<0.05)。Spearman相关分析结果显示,AAV患者血清Fuc_de与血中性粒细胞计数及红细胞沉降率(ESR)均呈负相关,Glc_de、Man_de及总血清降解单糖水平与ESR及C反应蛋白(CRP)均呈正相关(P<0.05)。ROC曲线分析结果显示,血清GalN_de水平预测MPO-ANCA阳性AAV疾病高度活动的ROC曲线下面积(AUC)为0.838(95%CI 0.695~0.982,P=0.009),最佳截断值为0.204 mmol/L,敏感度为83.3%,特异度为79.4%。结论 AAV患者血清糖萼降解后的单糖水平与疾病类型及疾病活动度相关。

Objective To explore changes of glycocalyx fractions in different types of anti-neutrophil cytoplasmic antibody-associated(ANCA)vasculitis(AAV)and their correlation with disease activity.Methods A total of 49 AAV patients(AAV group)and 53 healthy persons(control group)were enrolled.Six monosaccharides levels in serum after polysaccharide degradation were detected by PCR-assisted acid degradation and high performance liquid chromatography in subjects of above two groups.Serum degradation monosaccharide levels between AAV group and control group,between granulomatous polyvasculitis(GPA)and microscopic polyvasculitis(MPA)patients,between peroxidase(MPO)-ANCA and protease 3(PR3)-ANCA positive AAV patients,among inactive,active and highly active AAV patients were compared.Spearman correlation analysis was used to assess correlation between serum degraded monosaccharide levels and clinical index in AAV patients.Receiver operating characteristic(ROC)curve was used to analyze predictive value of serum degraded galactosamine(GalN_de)level for disease high activity in MPO-ANCA positive AAV.Results Serum degraded fucose(Fuc_de),GalN_de,degraded glucose(Glc_de),degraded mannose(Man_de)and total serum degraded monosaccharides levels in AAV group were all higher than those in control group(P<0.05).Total serum degraded monosaccharides level in MPA patients was higher than that in GPA patients(P<0.05).Total serum degraded monosaccharides level in MPO-ANCA positive AAV patients was higher than that in PR3-ANCA positive AAV patients(P<0.05).Serum GalN_de level was different significantly among inactive,active and highly active AAV patients,and it in highly active patients was higher than that in inactive patients(P<0.05).Spearman correlation analysis showed that serum fuc_de was negatively correlated with blood neutrophil count and erythrocyte sedimentation rate(ESR)in AAV patients,glc_de,man_de and total serum degraded monosaccharides were positively correlated with ESR and c-reactive protein(CRP)(P<0.05).ROC curve analysis showed that area under ROC curve(AUC)of serum galn_de level for predicting disease high activity in MPO-ANCA positive AAV was 0.838(95%CI 0.695~0.982,P=0.009),and optimal cut-off value was 0.204 mmol/L,sensitivity was 83.3%and specificity was 79.4%.Conclusion Monosaccharide levels of serum degraded glycocalyx are correlated with disease type and disease activity in AAV patients.