抗磷脂综合征患者血清α1抗胰蛋白酶的表达及临床意义
The abnormal expression of serum α1-antitrypsin in patients with antiphospholipid syndrome and its clinical significance
王悦冰 1罗永婧 1张梦瑶 1李春1
作者信息
- 1. 北京大学人民医院风湿免疫科,北京 100044
- 折叠
摘要
研究抗磷脂综合征(APS)患者血清中α1抗胰蛋白酶(A1AT)的表达及临床意义.方法 纳入在2019年1月至2022年6月就诊于北京大学人民医院的131例APS患者、48例疾病对照(8例类风湿关节炎、8例骨关节炎、32例系统性红斑狼疮)和49名健康对照.收集血清样本,采用ELISA测定样本中A1AT的浓度.分析A1AT与APS患者临床及实验室指标的相关性.采用GraphPad Prism 10.1.2进行统计学分析和作图.分类变量采取x2检验,连续变量经过正态分布检验,如服从正态分布,2组间比较采用独立样本t检验(方差齐)或Welch's t检验(方差不齐),多组间比较采用单因素方差分析;如不服从正态分布,以M(Q1,Q3)表示,2组间比较采用Mann-Whitney U检验,多组间比较采用Kruskal-Wallis H检验.如数据服从正态分布,采用Spearman相关性分析,否则采用Pearson相关性分析.结果 APS患者的血清A1AT浓度显著高于疾病对照[2 048.0(670.6,2 904.0)μg/ml 和 1 099.0(0,1 855.0)μg/ml,U=1 990,P＜0.001]高于健康对照[739.5.0(0,1 232.0)μg/ml,U=1 485,P＜0.001],疾病对照和健康对照之间差异无统计学意义[1 099.0(0,1855.0)μg/ml和739.5.0(0,1 232.0)μg/ml,U=924,P=0.060].同时存在不良孕产史和血栓病史的患者血清A1 AT平均浓度高于单纯产科[(3 212±1 744)μg/ml 和(1 965±1 500)μg/ml,t=2.27,P=0.026]和单纯血栓性 APS患者[(3 212±1 744)μg/ml和(1 963±1 745)μg/ml,t=2.01,P=0.048].同时患动脉和静脉血栓的患者血清A1AT平均浓度高于仅患静脉血栓的患者[(3 390±2 286)μg/ml和(2 148±1 648)μg/ml,t=3.04,P=0.004].复发血栓患者平均A1AT浓度高于单发血栓患者[(2 709±1 941)μg/ml和(1 805±1 627)μg/ml,t=2.10,P=0.040].以健康对照A1AT浓度的95％上限(1 066 μg/ml)作为截断值,TAPS患者中A1AT阳性者复发血栓风险高于阴性者[51.0％(25/49)和26.1％(6/23),x2=3.97,P=0.046].在实验室指标方面,APS患者的血清A1 AT浓度和ESR水平呈显著正相关(r=0.28,P=0.045),与C4水平呈显著负相关(r=-0.24,P=0.025),与纤维蛋白原(FIB)浓度呈显著正相关(r=0.25,P=0.027).A1AT具有良好诊断性能[受试者工作特征曲线下面积(AUC)(95％CI)=0.769(0.699,0.847),P＜0.001],灵敏度71.8％,特异度 73.7％,约登指数0.452.结论 A1AT在APS患者血清中显著升高,且可能和血栓事件严重程度有关.
Abstract
Objective To study the expression and clinical significance of alpha-1 antitrypsin(A1AT)in the serum of patients with antiphospholipid syndrome(APS).Methods The study recruited 131 patients with APS,48 patients with other autoimmune diseases(8 patients with rheumatoid arthritis,8 with osteoarthritis,and 32 with systemic erythematous sores),and 49 healthy people were recruited.The patients were admitted to Peking University People's Hospital during January 2019 to June 2022.A1AT expression in the serum of patients with APS and its clinical significance were investigated.Blood samples were collected and the concentration of Al AT in the samples was determined by enzyme-linked immunosorbent assay(ELISA).The correlation between Al AT and clinical and laboratory parameters of APS patients was analyzed.Statistical analysis and graphing were performed using GraphPadPrism 10.1.2.The categorical variables were subjected to the x2 test,and the continuous variables were subjected to the normal distribution test.If the sample were normally distributed,the independent sample t-test(with homogeneity of variance)or the Welch's t-test(with heterogeneity of variance)was used for comparison between the 2 groups,and one-way analysis of variance(ANOVA)was used for comparison among multiple groups;Otherwise,and the variables were described asM(Qi,Q3),the Mann Whitney U-test was used for comparison between 2 groups,and the Kruskal-Wallis U-test was used for comparison among multiple groups.The Kruskal-Wallis H test was used for multiple comparisons.If the samples were normally distributed,Spearman correlation analysis was used to determine the correlation,otherwise,Pearson correlation analysis was used.Results The serum A1AT concentrations were significantly higher in APS patients than in patients with other autoimmune diseases[2 048.0(670.6,2 904.0)μg/ml vs.1 099.0(0,1 855.0)μg/ml,U=1 990,P＜0.001]and healthy people[2 048.0(670.6,2 904.0)μg/ml vs.739.5(0,1 232.0)μg/ml,U=1 485,P＜0.001].No statistically significant difference was observed between patients with other autoimmune diseases and healthy people[1 099.0(0,1 855.0)μg/ml vs.739.5(0,1 232.0)μg/ml,U=924,P=0.060].Mean serum A1AT concentrations were also higher in patients with both a history of adverse pregnancy and thrombosis than in those with morbid pregnancy only[(3 212±1 744)μg/ml vs.(1 965±1 500)μg/ml,t=2.27,P=0.026]and thrombosis only[(3 212±1 744)μg/ml vs.(1 963±1745)μg/ml,t=2.01,P=0.048].Mean serum A1AT concentrations were higher in patients with both arterial and venous thrombosis than in those with only venous thrombosis[(3 390±2 286)μg/ml vs.(2 148±1 648)μg/ml,t=3.04,P=0.004].The mean A1AT concentration was higher in patients with recurrent thrombosis than in patients with single thrombosis[(2 709±l 941)μg/ml vs.(1 805±1 627)μg/ml,t=2.10,P=0.040].Using the 95％upper limit of A1AT concentration in healthy controls(1 066 μg/ml)as a cut-off value,the risk of recurrent thrombosis was higher in A1AT-positive than negative TAPS patients[51.0％(25/49)vs.26.1％(6/23),x2=3.97,P=0.046].In terms of laboratory indicators,there was a significant positive correlation between serum A1AT concentration and ESR level(r=0.28,P=0.045),a significant negative correlation with C4 level(r=-0.24,P=0.025).There was a significant positive correlation with fibrinogen(FIB)concentration(r=0.25,P=0.027).A1AT was an effective diagnostic marker of APS[AUC(95％CI)=0.769(0.699,0.847),P＜0.001],with a sensitivity of 71.8％,a specificity of 73.7％,and Youden index of 0.452.Conclusion A1AT was is significantly elevated in the serum of patients with APS and may be associated with the severity of thrombotic event.
关键词
抗磷脂综合征/α1抗胰蛋白酶/酶联免疫吸附Key words
Antiphospholipid syndrome/α-1 antitrypsin/ELISA引用本文复制引用
基金项目
北京市科技计划项目(Z191100006619110)
中华国际医学交流基金会(Z-2018-40-2101)
北京大学人民医院研究与发展基金(RD 2022-66)
出版年
2024
NETL
NSTL
万方数据