抗磷脂综合征患者血浆中补体激活片段的水平及临床意义
항린지종합정환자혈장중보체격활편단적수평급림상의의
The level and significance of plasma complement activation products in patients with anti-phospho-lipid syndrome
  • 万方数据
    中华风湿病学杂志 중화풍습병학잡지
    CHINESE JOURNAL OF RHEUMATOLOGY
    2015年 5期 292-296 ,共5页

    王青松%周滢波%方璇%李向培%汪国生%钱龙%陈玲%吴竞生%厉小梅

    왕청송%주형파%방선%리향배%왕국생%전룡%진령%오경생%려소매

    抗磷脂综合征%抗体,抗磷脂%细胞因子类%补体激活片段 抗燐脂綜閤徵%抗體,抗燐脂%細胞因子類%補體激活片段
    항린지종합정%항체,항린지%세포인자류%보체격활편단
    Antiphospholipid syndrome%Antibodies,antiphospholipid%Cytokines%Complement activation products
    目的 检测APS患者血浆中补体激活片段C4d、C5b-9,炎性细胞因子TNF-α、IFN-γ、IL-1β、IL-6、血管内皮生长因子(VEGF)的浓度水平,探讨其临床意义.方法 选取符合2006年悉尼国际APS会议修订的分类标准的APS患者60例(原发性APS 37例、继发性APS 23例),另选健康成年人20名、健康孕妇10名作为健康对照组,利用ELISA法检测APS组及对照组血浆中的C4d、C5b-9,以及炎性细胞因子TNF-α、IFN-γ 、IL-1β、IL-6 、VEGF的水平,分析其在血浆中的变化及与实验室指标之间的相关性.2组间比较符合正态分布的计量资料用独立样本t检验,不符合正态分布的计量资料用秩和检验,变量间相关性分析采用Pearson相关或Spearman相关分析.结果 ①APS患者血浆中补体C5b-9浓度显著高于健康对照组[2 766.59(480.41,12 993.05) μg/ml与712.24 (340.96,2 770.26) μg/ml,Z=-6.347,P＜0.01],C4d浓度高于健康对照组[5.51(0.12,20.78) μg/ml与1.83(0.44,8.40) μg/ml,Z=-4.58,P＜0.01];APS患者血浆中炎性细胞因子TNF-α、IFN-γ、IL-1β水平高于健康对照组[27,86(1.54,488.53) pg/ml与24.15(1.51,54.38) pg/ml,Z=1.542,P＜0.05;4.36(1.12,41.98) pg/ml与1.53 (0.94,2.89) pg/ml,Z=1.505,P＜0.05;5.42(1.08,19.06) pg/ml与2.16 (0.26,5.26) pg/ml,Z=1.793,P＜0.05];IL-6 、VEGF水平低于健康对照组[1.93(1.39,5.42) pg/ml与2.97(1.41,7.26) pg/ml,Z=2.177,P＜0.01;66.58(5.13,177.38) pg/ml与108.34(50.95,290.55) pg/ml,Z=1.406,P＜0.05].②APS患者血浆中补体C5b-9浓度与ESR、抗心磷脂抗体(ACA) IgG、抗β2糖蛋白Ⅰ(β2-GP Ⅰ)抗体之间呈正相关(r=0.602,P＜0.01;r=0.287,P＜0.05;r=0.386,P＜0.01),与补体C3、C4无相关性(r=-0.004,P＞0.05;r=-0.043,P＞0.05);APS患者血浆中补体C4d浓度与补体C3、C4之间呈负相关(r=-0.951,P＜0.01;r=-0.803,P＜0.01),与ACA IgG、ESR无相关性(P＞0.05).结论 补体系统在APS中被激活,血浆中产生的补体裂解片段C4d、C5b-9浓度、炎性细胞因子TNF-α、IFN-γ、IL-1β水平明显升高,IL-6、VEGF水平明显减低,提示上述变化与病情有密切关系,从而揭示补体的异常激活及炎性细胞因子的产生可能参与了APS发病过程.
    목적 검측APS환자혈장중보체격활편단C4d、C5b-9,염성세포인자TNF-α、IFN-γ、IL-1β、IL-6、혈관내피생장인자(VEGF)적농도수평,탐토기림상의의.방법 선취부합2006년실니국제APS회의수정적분류표준적APS환자60례(원발성APS 37례、계발성APS 23례),령선건강성년인20명、건강잉부10명작위건강대조조,이용ELISA법검측APS조급대조조혈장중적C4d、C5b-9,이급염성세포인자TNF-α、IFN-γ 、IL-1β、IL-6 、VEGF적수평,분석기재혈장중적변화급여실험실지표지간적상관성.2조간비교부합정태분포적계량자료용독립양본t검험,불부합정태분포적계량자료용질화검험,변량간상관성분석채용Pearson상관혹Spearman상관분석.결과 ①APS환자혈장중보체C5b-9농도현저고우건강대조조[2 766.59(480.41,12 993.05) μg/ml여712.24 (340.96,2 770.26) μg/ml,Z=-6.347,P＜0.01],C4d농도고우건강대조조[5.51(0.12,20.78) μg/ml여1.83(0.44,8.40) μg/ml,Z=-4.58,P＜0.01];APS환자혈장중염성세포인자TNF-α、IFN-γ、IL-1β수평고우건강대조조[27,86(1.54,488.53) pg/ml여24.15(1.51,54.38) pg/ml,Z=1.542,P＜0.05;4.36(1.12,41.98) pg/ml여1.53 (0.94,2.89) pg/ml,Z=1.505,P＜0.05;5.42(1.08,19.06) pg/ml여2.16 (0.26,5.26) pg/ml,Z=1.793,P＜0.05];IL-6 、VEGF수평저우건강대조조[1.93(1.39,5.42) pg/ml여2.97(1.41,7.26) pg/ml,Z=2.177,P＜0.01;66.58(5.13,177.38) pg/ml여108.34(50.95,290.55) pg/ml,Z=1.406,P＜0.05].②APS환자혈장중보체C5b-9농도여ESR、항심린지항체(ACA) IgG、항β2당단백Ⅰ(β2-GP Ⅰ)항체지간정정상관(r=0.602,P＜0.01;r=0.287,P＜0.05;r=0.386,P＜0.01),여보체C3、C4무상관성(r=-0.004,P＞0.05;r=-0.043,P＞0.05);APS환자혈장중보체C4d농도여보체C3、C4지간정부상관(r=-0.951,P＜0.01;r=-0.803,P＜0.01),여ACA IgG、ESR무상관성(P＞0.05).결론 보체계통재APS중피격활,혈장중산생적보체렬해편단C4d、C5b-9농도、염성세포인자TNF-α、IFN-γ、IL-1β수평명현승고,IL-6、VEGF수평명현감저,제시상술변화여병정유밀절관계,종이게시보체적이상격활급염성세포인자적산생가능삼여료APS발병과정.
    Objective To investigate the levels of plasma complement activation products C4d,C5b-9 and inflammatory cytokines tumor necrosis factor (TNF)-α,interferon (IFN)-γ,inteleukin (IL)-1β,IL-6,vascular endothelial growth factor (VEGF) in patients with antiphospholipid syndrome (APS).Methods The expression levels of plasma C4d,C5b-9,TNF-α,IFN-γ,IL-1β,IL-6,VEGF in 60 APS patients and 30 healthy controls were analyzed by enzyme linked immunosorbent assay (ELISA).The relationship between the C4d,C5b-9,TNF-α,IFN-γ,IL-1β,IL-6,VEGF and clinical data was analyzed in APS patients.Independent sample t test was used to compare the difference between the two groups if the data was in a normal distribution pattern and those data that were not accordance with normal distribution were analyzed by Mann-Whitney Utest.Pearson correlation analysis or Spearman correlation analysis were used for variables related analysis.Results ① Significant differences were found in the plasma levels of C5b-9,C4d,TNF-α,IFN-γ,IL-1β,IL-6,VEGF between APS patients and healthy controls.C5b-9,C4d were significantly higher in APS patients than those in the controls[2 766.59(480.41,12 993.05) μg/ml and 712.24(340.96,2 770.26) μg/ml,Z=-6.347,P＜0.01;5.51 (0.12,20.78) μg/ml and 1.83 (0.44,8.40) μg/ml,Z=-4.58,P＜0.01].TNF-α、IFN-γ、IL-1 β were significantly higher in APS patients than those in the controls as well [27,86 (1.54,488.53) pg/ml and 24.15 (1.51,54.38) pg/ml,Z=1.542,P＜0.05;4.36 (1.12,41.98) pg/ml and 1.53 (0.94,2.89) pg/ml,Z=1.505,P＜0.05;5.42 (1.08,19.06) pg/ml and 2.16 (0.26,5.26) pg/ml,Z=1.793,P＜0.05].The levels of IL-6 and VEGF were significantly lower in patients than those in the controls [1.93(1.39,5.42) pg/ml and 2.97(1.41,7.26) pg/ml,Z=2.177,P＜0.01;66.58 (5.13,177.38) pg/ml and 108.34 (50.95,290.55) pg/ml,Z=1.406,P＜0.05].② Significant positive correlation was observed between C5b-9 and ESR,anticardiolipin antibody (ACA) immunoglobulin (Ig) G,anti-β2-glycoprotein Ⅰ antibodies (r=0.602,P＜0.01;r=0.287,P=0.039;r=0.386,P＜0.01).No correlation was found between C5b-9 and C3、C4.Significant negative correlation was observed between C4d and C3,C4 (r=-0.951,P＜0.01;r=-0.803,P＜0.01).No correlation was found between C4d and IgG type ACA,and ESR.Conclusion The complement system is activated in APS,the plasma levels of complement activation products C5b-9,C4d and inflammatory cytokines TNF-α,IFN-γ,IL-1β are significantly increased.The plasma levels of IL-6,VEGF are significantly decreased.These results demonstrate that complement activation and inflammatory cytokines may play an important role in the pathogenesis of APS.
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