血清学抗中性粒细胞胞浆抗体在炎症性肠病中的表达及其诊断价值

Expression and diagnostic value of serological anti-neutrophil cytoplasmic antibody in inflammatory bowel disease

目的通过检测血清核周型抗中性粒细胞胞浆抗体(p-ANCA)、胞浆型ANCA(c-ANCA)、蛋白酶3(PR3)-ANCA、髓过氧化物酶(MPO)-ANCA血清学自身抗体在炎症性肠病(IBD)的表达水平,探讨单独和联合检测4种抗体对IBD诊断、鉴别诊断的临床意义。方法选取2018年5月至2021年2月于惠州市第一人民医院确诊的123例IBD患者作为研究对象,按照疾病类型分为溃疡性结肠炎(UC)组78例,克罗恩病(CD)组45例,选取同期的非IBD肠道疾病患者56例作为疾病对照组,健康体检者30名作为正常对照组,采用间接免疫荧光法(IIF法)检测p-ANCA、c-ANCA的表达水平,采用酶联免疫法(ELISA法)检测PR3-ANCA、MPO-ANCA的表达水平,比较各组的抗体表达差异,分析4种抗体对IBD的诊断效能,不同临床特征的UC患者的p-ANCA表达情况。结果四组患者的p-ANCA、c-ANCA、PR3-ANCA、MPO-ANCA及4种抗体联合检测的阳性率比较,差异有统计学意义(P<0.01)。UC组患者的p-ANCA高于CD组、疾病对照组、正常对照组,c-ANCA、PR3-ANCA、联合检测高于疾病对照组、正常对照组,MPO-ANCA高于疾病对照组,差异有统计学意义(P<0.008)。CD组的c-ANCA及联合检测高于疾病对照组、正常对照组,MPO-ANCA高于疾病对照组,差异有统计学意义(P<0.008)。4种抗体联合检测诊断IBD的敏感度和准确度最高,分别为66.7%、75.1%;PR3-ANCA和MPO-ANCA的特异度最高,均为95.3%。p-ANCA、c-ANCA、PR3-ANCA、MPO-ANCA的阳性预测值分别为91.2%、89.9%、87.9%、88.9%、88.2%;阴性预测值分别为53.3%、60.0%、46.6%、47.4%、64.7%。PR3-ANCA诊断UC的特异度最高,但敏感度仅为26.9%,p-ANCA诊断UC的效能较好,联合检测能提高诊断UC的敏感度,但特异度有所下降,c-ANCA诊断CD的敏感度和特异度均不高,鉴别诊断效能较低。P-ANCA在中重度UC患者中阳性率高于轻度UC患者,病变部位在广泛结肠的患者占比高于其他部位,差异有统计学意义(P<0.05)。结论PR3-ANCA、p-ANCA、c-ANCA、MPO-ANCA对IBD的诊断和鉴别诊断有一定的辅助价值,且联合检测比单独检测价值更高,p-ANCA可能有利于鉴别诊断UC和CD,p-ANCA的表达与UC的严重程度,病变部位相关,对UC的病情评估有一定的潜在辅助作用,值得进一步研究。

Objective By detecting the expression levels of serum perinuclear anti-neutrophil cytoplasmic antibody(p-ANCA),cytoplasmic ANCA(c-ANCA),proteinase 3(PR3)-ANCA,myeloperoxidase(MPO)-ANCA serological autoantibodies in inflammatory bowel disease(IBD),to investigate the clinical significance of single and combined detection of four antibodies in the diagnosis and differential diagnosis of IBD.Methods A total of 123 patients with IBD diagnosed in Huizhou First People′s Hospital from May 2018 to February 2021 were selected as the research objects.According to the disease type,they were divided into ulcerative colitis(UC)group(n=78)and Crohn′s disease(CD)group(n=45).Fifty-six patients with non-IBD intestinal diseases were selected as the disease control group,and 30 healthy subjects were selected as the normal control group.The expression levels of p-ANCA and c-ANCA were detected by indirect immunofluorescence(IIF)method,and the expression levels of PR3-ANCA and MPO-ANCA were detected by enzyme-linked immunosorbent assay(ELISA).The difference of antibody expression in each group was compared,and the diagnostic efficacy of the four antibodies for IBD and the expression of p-ANCA in UC patients with different clinical characteristics were analyzed.Results There were significant differences in the positive rates of p-ANCA,c-ANCA,PR3-ANCA,MPO-ANCA and the combined detection of four antibodies among the four groups (P<0.01). P-ANCA of UC group was higher than that of CD group, disease control group and normal control group, c-ANCA, PR3-ANCA and combined detection were higher than those of disease control group and normal control group, and MPO-ANCA was higher than that of disease control group, and the differences were statistically significant (P<0.008). The c-ANCA and combined detection in CD group were higher than those in disease control group and normal control group, and MPO-ANCA was higher than that in disease control group, and the differences were statistically significant (P<0.008). The sensitivity and accuracy of the combined detection of four antibodies in the diagnosis of IBD were the highest, which were 66.7% and 75.1%, respectively. PR3-ANCA and MPO-ANCA had the highest specificity (95.3%). The positive predictive values of p-ANCA, c-ANCA, PR3-ANCA and MPO-ANCA were 91.2%, 89.9%, 87.9%, 88.9% and 88.2%, respectively. The negative predictive values were 53.3%, 60.0%, 46.6%, 47.4% and 64.7%, respectively. PR3-ANCA has the highest specificity in the diagnosis of UC, but the sensitivity is only 26.9%. p-ANCA has a good diagnostic efficiency in the diagnosis of UC, and combined detection can improve the sensitivity of UC, but the specificity is decreased. C-ANCA has a low sensitivity and specificity in the diagnosis of CD, and the differential diagnostic efficiency is low. The positive rate of p-ANCA in patients with moderate to severe UC was higher than that in patients with mild UC, and the proportion of patients with lesions in extensive colon was higher than that in other parts, and the differences were statistically significant (P<0.05). Conclusion PR3-ANCA, p-ANCA, c-ANCA and MPO-ANCA have certain auxiliary value in the diagnosis and differential diagnosis of IBD, and the combined detection is more valuable than the single detection. p-ANCA may be beneficial to the differential diagnosis of UC and CD. The expression of p-ANCA is related to the severity and lesion location of UC, and has a potential auxiliary role in the evaluation of UC, which is worthy of further study.