系统性红斑狼疮患者ANA免疫荧光核型分布及其与病情发展的相关性研究

Correlation between ANA Immunofluorescence Karyotype Distribution and Disease Development in Patients with Systemic Lupus Erythematosus

目的 研究系统性红斑狼疮(systemic lupus erythematosus,SLE)患者抗核抗体(antinuclear antibody,ANA)免疫荧光核型分布特征及其与病情发展的相关性。方法 选取2018年8月~2022年8月期间于四川省南充市中心医院收治的300例SLE患者作为SLE组,以同期收治的50例非SLE的其他自身免疫性疾病患者作为非SLE组、健康体检的50例健康人群作为健康对照组。应用多重微珠流式免疫荧光发光法检测血清ANA阳性表达情况,应用间接免疫荧光(indirect immunofluorescence,IIF)法检测ANA免疫荧光核型,比较三组ANA阳性率,分析不同临床特征SLE患者ANA阳性率、ANA免疫荧光核型分布情况。根据SLE患者病情发展情况分为SLE活动组111例、SLE非活动组189例,比较两组ANA阳性率和免疫荧光核型分布情况,采用受试者工作(receiver operating characteristic,ROC)曲线分析ANA预测SLE患者病情发展的价值,经二元Logistic回归分析影响SLE患者病情发展的危险因素,采用Spearman法分析ANA与SLE患者病情发展的相关性。结果 健康对照组、非SLE组和SLE组ANA阳性率(4.00%,56.00%,96.00%)依次升高,差异具有统计学意义(χ^(2)=171.500,P <0.05)。ANA阳性率与SLE患者有关节炎、病情发展有关(P <0.05)。288例ANA阳性SLE患者免疫荧光核型包括核颗粒型[60.07%(173/288)]、核均质型[31.94%(92/288)]、胞浆颗粒型[3.47%(10/288)]、核仁型[2.78%(8/288)]和着丝点型[1.74%(5/288)],以核颗粒型最为多见,其次为核均质型。与SLE非活动组比较,SLE活动组ANA阳性率(99.10%vs 94.18%)、ANA免疫荧光核型中核颗粒型比例(69.37%vs 50.79%)升高,差异具有统计学意义(χ^(2)=4.407,9.884,均P <0.05)。与SLE非活动组比较,SLE活动组肾脏病变比例、SLEDAI评分、IgA水平、IgM水平和IgG水平升高,而C3水平和C4水平降低,差异具有统计学意义(t/χ^(2)=10.793~96.751,均P <0.05)。由Logistic回归分析结果构建预测模型:Logit(P)=1.854×(ANA阳性)+1.872×(ANA核颗粒型)+1.278×(SLEDAI评分)+1.651×(IgA)+1.795×(IgM)+1.885×(IgG)+1.684×(C3)+1.463×(C4)+1.221×(肾脏病变)-10.797。经ROC曲线分析显示,预测模型预测活动期SLE的曲线下面积为0.895(95%CI:0.800~0.943),高于ANA预测[0.785(95%CI:0.714~0.844)]。相关性分析显示,ANA表达与SLE患者病情发展呈正相关关系(r=0.309,P <0.05)。结论 SLE患者ANA阳性率升高,免疫荧光核型分布以核颗粒型常见,与患者病情发展有关,可用于SLE病情发展的评估。

Objective To study the distribution characteristics of antinuclear antibodies(ANA)immunofluorescence karyotypes in patients with systemic lupus erythematosus(SLE)and their correlation with the development of the patient’s condition.Methods 300 SLE patients admitted to Nanchong Central Hospital in Sichuan Province from August 2018 to August 2022 were selected as the SLE group,50 patients with other autoimmune diseases other than SLE admitted in the same period were selected as the non SLE group,and 50 healthy people in health examination were selected as the healthy control group.Multiple bead flow immunofluorescence luminescence method was used to detect the positive expression of serum ANA,and indirect immunofluorescence(IIF)method was used to detect ANA immunofluorescence karyotypes.Three groups of ANA positive rates were compared,and the ANA positive rates and distribution of ANA immunofluorescence karyotypes in SLE patients with different clinical characteristics were analyzed.According to the disease activity of SLE patients,111 cases were divided into SLE active group and 189 cases were SLE inactive group.The positive rate of ANA and the distribution of immunofluorescence karyotypes were compared between the two groups.The receiver operating characteristic(ROC)was used to analyze the value of ANA in predicting the progression of SLE patients,and binary logistic regression was used to analyze the risk factors affecting the progression of SLE patients.The Spearman method was used to analyze the correlation between ANA and the progression of SLE patients.Results The ANA positive rates(4.00%,56.00%,96.00%)in the healthy control group,non SLE group,and SLE group increased sequentially,with statistically significant differences(χ^(2)=171.500,P<0.05).The positive rate of ANA was associated with arthritis and disease progression in SLE patients(P<0.05).The immunofluorescence karyotypes of 288 ANA positive SLE patients included nuclear granular type[60.07%(173/288)],nuclear homogeneous type[31.94%(92/288)],cytoplasmic granular type[3.47%(10/288)],nucleolar type[2.78%(8/288)]and centrocentric type[1.74%(5/288)],the nuclear granular type was the most common,followed by the nuclear homogeneous type.Compared with inactive SLE group,the positive rate of ANA(99.10%vs 94.18%)and the proportion of nuclear particle type in ANA immunofluorescence karyotype(69.37%vs 50.79%)were significantly higher in active SLE group(χ^(2)=4.407,9.884,all P<0.05).Compared with the inactive SLE group,the proportion of kidney lesions,SLEDAI score,IgA,IgM,IgG levels,C3,C4 levels were increased in the active SLE group,and the differences were statistically significant(t/χ^(2)=10.793~96.751,all P<0.05).The prediction model was constructed by Logistic regression analysis results:Logit(P)=1.854×(ANA positive)+1.872×(ANA granulotype)+1.278×(SLEDAI score)+1.651×(IgA)+1.795×(IgM)+1.885×(IgG)+1.684×(C3)+1.463×(C4)+1.221×(Kidney disease)-10.797.ROC curve analysis showed that the area under the curve of SLE predicted by the prediction model was 0.895(95%CI:0.800~0.943),which was higher than ANA prediction[0.785(95%CI:0.714~0.844)].Correlation analysis showed that ANA expression was positively correlated with the development of SLE patients(P<0.05).Conclusion ANA positive rate increases in SLE patients,and the distribution of immunofluorescent karyotypes was common with nuclear granules,which was related to the disease development of patients and can be used for the assessment of the disease development of SLE.