抗核抗体系列及补体检测对狼疮性肾炎的诊断意义

目的 探讨抗核抗体系列及补体检测对系统性红斑狼疮(SLE)伴狼疮性肾炎(LN)诊断的意义.方法 对1 699例SLE患者和120例健康体检者采用间接免疫荧光法测定抗核抗体(ANA),应用欧蒙印迹法测定抗核抗体系列,应用散射比浊法测定补体C3、C4.结果 1699例SLE患者,LN组921例,ANA阳性率为97.4％;不伴LN组778例,ANA阳性率为98.2％;与对照组比较,r=0.983,P=0.001,差异有统计学意义.LN组的抗组蛋白抗体,抗核小体抗体,抗双链DNA抗体阳性率分别为49.3％、59.8％、63.3％;不伴LN组分别为21.5％、35％、47.9％;差异有统计学意义(r=0.452,P=0.007).抗线粒体-2抗体和抗着丝点抗体阳性率,LN组与不伴肾炎组比较差异有统计学意义(r=0.291,P=0.015).当抗组蛋白抗体+抗核小体抗体+抗双链DNA抗体同时阳性时,LN患者其补体C3,C4水平比这三种抗体非同时阳性时的水平均更低,差异有统计学意义(r=0.583,P=0.009).结论 抗核抗体系列及补体的血清学检测对诊断LN及其预后判断、疗效观察等具有重要意义.     

抗核抗体和抗核抗体谱在系统性红斑狼疮中的价值探讨

目的 探讨检测抗核抗体和抗核抗体谱在诊断系统性红斑狼疮中的应用价值.方法 选取我院风湿免疫科确诊为系统性红斑狼疮(SLE)的患者50人为实验组,其它结缔组织病患者104例,包括干燥综合征(SS)14例、类风湿关节炎(RF)62例、混合性结缔组织病(MCTD)28例和非自身免疫病患者53例为对照组.检测其ANA定量值和ANA抗体谱的表达.结果 ANA在SLE中表达较高,但与MCTD和SS患者间差异无统计学意义(P＞0.05).抗核抗体谱中与SLE相关性较高的抗体中仅抗nRNP与抗dsDNA与对照组间差异有统计学意义(P＜0.05).抗核抗体联合后灵敏度可大幅提高的组合为nRNP+dsDNA+SSA60,在SLE与SS中无统计学意义(P＞0.05).结论 抗nRNP抗体,抗SSA/Ro60抗体,抗dsDNA抗体,抗SSA/Ro52抗体在诊断SLE中灵敏度尚可,联合诊断并不能大幅度提高诊断价值.     

自身抗体检测在儿童系统性红斑狼疮诊断中的意义

目的探讨抗核抗体(ANA)、抗双链DNA(ds-DNA)、抗ENA抗体检测在儿童系统性红斑狼疮(SLE)诊断中的价值.方法利用酶免疫斑点技术对56例SLE患儿的抗核抗体、抗ds-DNA、抗ENA抗体进行检测.结果56例SLE患儿ANA阳性率最高94.6%,抗ds-DNA阳性率为55.4%,抗Sm/RNP阳性率64.8%,抗SSA/SSB阳性率60.7%.结论SLE患者血清中存在多种自身抗体,自身抗体的联合检测对SLE的诊断和病情的监测有着重要的意义.     

ANA和ENA检测在自身免疫性疾病中的应用评价

探讨抗核抗体和抗可溶性核抗原抗体的不同检测方法对自身免疫性疾病诊断的指导意义。回顾性分析2007年1月至2009年10月间在长征医院就诊的患者血清自身抗体的检测结果,549位患者,其中自身免疫病患者224例,非自身免疫病325例,所有患者血清同时检测ANA和ENA。以Hep-2细胞/肝组织为基质的间接免疫荧光法检测ANA,免疫印迹法检测ENA。两种检测方法产生4种检出模式:ANA+/ENA+、ANA-/ENA-、ANA+/ENA-和ANA-/ENA+。前两种模式共占检测的62.84%。ANA和ENA在自身免疫病患者中的阳性率(63.4%和58.5%)显著高于非自免病患者(16.9%和25.2%),ANA和ENA在自身免疫病组和非自身免疫病组间阳性率比较,差异有统计学意义(P<0.01)。两检测结果仅在MCTD和SLE患者中存在相关性(P<0.01),在其他观察组中不存在相关性(P>0.05)。间接免疫荧光法相对费时,而且需要操作者具备一定的经验,作为初筛实验,ANA的检测较ENA有更高的灵敏度,两者联合检测则将有利于提高检测的灵敏度和可靠性。     

自身抗体联合检测对系统性红斑狼疮的诊断价值

研究抗核抗体(ANA)、抗双链DNA(ds-DNA)抗体、抗Smith(Sm)抗体、抗核小体抗体(AnuA)和抗核糖体P蛋白抗体(ARPA)5种自身抗体单项及联合检测系统性红斑狼疮(SLE)诊断中的价值.测定了66例SLE患者和50例其他疾病患者(对照组)血清中的自身抗体.以间接免疫荧光法测定ANA;免疫印迹法测定抗ds-DNA抗体、抗Sm抗体、AnuA和ARPA.结果显示,在66例SLE患者中ANA、抗ds-DNA抗体、抗Sm抗体、AnuA和ARPA的阳性率分别为92.4%、27.2%、42.4%、71.2%和16.6%,均明显高于对照组(32%、2%、2%、4%和2%)(P＜0.01);ANA、AnuA的敏感性明显高于其他3种抗体(P＜0.01);ANA、抗ds-DNA抗体、抗Sm抗体、AnuA和ARPA的特异性分别为68.0%、98.0%、98.0%、96.0%和98.0%.结论:抗ds-DNA抗体、抗Sm抗体、AnuA和ARPA等4种自身抗体对SLE的检测有很高的特异性,且有明显的互补作用,联合检测能提高对SLE检测的敏感性.     

活性染色质诱导抗核抗体生成及肾损伤

系统性红斑狼疮 (SLE )的病因和诱导抗核抗体 (ANA )生成的激发原迄今不明。本实验试图用ConA活化淋巴细胞的染色质免疫同系BALB/c小鼠 ,寻找诱导ANA生成的真正免疫原 ,阐明SLE发生的激发原是自身活化细胞的核成分 ,而且证明它所诱导的ANA具有致病性。从ConA活化的脾细胞中提取染色质 ,然后免疫同系BALB/c小鼠 ,用ELISA方法测定IgG类抗双链DNA (dsDNA )、抗组蛋白抗体 ,用免疫荧光法检测抗核抗体核型和免疫复合物沉积 ,用免疫印迹法测定抗核抗体谱 ,在光镜下检测肾损伤及电镜下检测肾小球沉积物 ,用考马斯亮蓝法检测尿蛋白含量。结果显示 ,活性染色质能诱导IgG类抗dsDNA、抗组蛋白等多种抗核抗体生成 ,且肾小球有显著免疫复合物沉积和蛋白尿形成。该实验表明 ,活化淋巴细胞的染色质是诱导SLE发生的真正自身免疫原。     

264例系统性红斑狼疮患者抗磷脂抗体与抗核抗体、抗双链DNA抗体关系的研究

目的 分析系统性红斑狼疮(SLE)患者抗磷脂抗体(APL)特征及其与抗核抗体(ANA)核型、抗双链DNA抗体(anti-dsDNA)之间的关系，为SLE患者系统性治疗提供参考。方法 选取2018年1月至2021年12月就诊于首都医科大学附属北京同仁医院的SLE患者264例，回顾性分析患者APL[狼疮抗凝物(LA)、抗心磷脂抗体(ACA)、和抗β₂糖蛋白I抗体(anti-β₂GPI)]与ANA核型特征、anti-dsDNA的关系。结果 264例患者中164例(62.12%)LA阳性、22例(8.33%)ACA阳性、38例(14.39%)anti-β₂GPI阳性、260例(98.48%)ANA阳性和136例(51.52%)anti-dsDNA阳性。在164例LA阳性的SLE患者中，LA弱阳性表达92例(56.10%),LA阳性表达52例(31.71%),LA强阳性表达20例(12.19%)。ACA、anti-β₂GPI和LA均阳性16例。260例ANA阳性的SLE患者中，胞核均质型48例(18.46%)...     

淋巴细胞的活化和抗核抗体的生成

抗核抗体 (ANA )是系统性风湿性疾病的标志性抗体。然而 ,有关ANA产生的启动原目前尚不完全清楚。我们自 90年代初开始了ANA启动原的研究 ,获得了一系列研究结果 ,从而提出以下ANA生成的启动原的新观点 :(1 )自身核抗原的改变是驱动ANA生成的启动原 ;(2 )活化淋巴细胞的核抗原发生量与性质的改变 ,是引起ANA生成的最主要原因 ;(3 )系统性红斑狼疮 (SLE )患者外周血B和T淋巴细胞已被活化 ;(4)在一定条件下活化淋巴细胞才能诱导ANA生成 ;(5 )ANA生成是有规律的 ,先出现少数ANA ,后陆续出现众多ANA ,即表位扩展 ;(6 )SLE反应 (自身免疫性 )在一定条件下可发展成SLE样病 (自身免疫病 )。此观点对临床免疫学和基础免疫学的研究将有重要意义     

不同状态下系统性红斑狼疮与补体的相关性分析

目的观察不同状态下系统性红斑狼疮(systemic lupus erythematosus,SLE)患者补体C3、C4水平变化并探讨其临床意义。方法选取326例系统性红斑狼疮患者作为本次研究对象。按照抗双链DNA(dsDNA)抗体阴阳性分为dsDNA阴性及阳性组,按照抗核抗体(ANA)核型分为阴性、均质型、斑点型、核仁型及其他型组。比较两种分组方式下C3、C4的结果。结果dsDNA阳性患者C3、C4水平均低于阴性患者,差异具有统计学意义(P<0.05);ANA为均质型、斑点型及其他型患者C3、C4水平均低于ANA阴性组及核仁型组患者,差异具有统计学意义(P<0.05)。结论不同状态下系统性红斑狼疮患者补体C3、C4水平存在差异,联合检测补体C3、C4有助于对SLE病情活动性及自身抗体类型作出判断。     

免疫性血小板减少症患者血清ANA、BAFF异常及临床意义的研究

目的:探讨成人免疫性血小板减少症(ITP)患者血清抗核抗体(ANA)临床特点及与B细胞活化因子(BAFF)之间的关系以及预后意义。方法:分析初治ITP患者70例,研究患者免疫学异常特点,观察患者ANA与临床表现、近期疗效的关系;动态分析ITP患者43例,观察有无进展为SLE等结缔组织病;ELISA检测ANA阳性患者与阴性患者BAFF有无差异。结果:ITP患者存在多项免疫异常,ANA阳性、抗干燥综合征抗原(SSA)阳性、IgG增加比例高;起病时ANA阳性患者血小板计数(PLT)较ANA阴性患者低,出血症状较ANA阴性患者重;ANA阳性患者BAFF水平高于阴性患者;ANA阳性患者对激素治疗的近期疗效优于ANA阴性患者;43例动态分析患者平均随访期限为(48.44±4.80)月,2例随访过程中进展为SLE,均为较高滴度(分别为6.23和4.1)的ANA阳性患者。结论:起病时ANA阳性患者病情较重,对激素治疗的近期疗效较ANA阴性患者好,ANA阳性患者BAFF水平高,ANA可能与ITP发病及病情进展有一定关系。     

年龄、职业和免疫因素与系统性红斑狼疮及狼疮性肾炎的关系

目的评价年龄、职业和免疫冈素与系统性红斑狼疮及狼疮性。肾炎的关系。方法收集2009年本院风湿免疫科住院的172例系统性红斑狼疮患者,将病人分为狼疮性肾炎和非狼疮性肾炎组,分析两组病人的年龄分布情况,并对这两组病人的抗核抗体（ANA）、抗ENA抗体和补体C3、C4进行检测。结果本研究的系统性红斑狼疮病人中,农民患者人数最多,占38．3％;狼疮性肾炎和非狼疮性肾炎组患者的年龄分布一致,均主要集中存15～44年龄段;两组患者的核型和15种抗体的阳性率没有统计学差异;狼疮性肾炎和非狼疮性肾炎组的C3与C4值均具有正相关的趋势（相关系数为0．85）,并且狼疮性肾炎组病人的C3值明显低于非狼疮性肾炎组（P=0．03）。结论性别、年龄、工作生活环境及ANA、C3、C4对系统性红斑狼疮的诊断具有很大的价值,其中补体c3对评价系统性红斑狼疮和狼疮性肾炎有较大的意义。     

四种自身抗体联检对SLE诊断的临床价值

目的：探讨抗核抗体（ANA）、抗双链DNA（ds-DNA）抗体、抗Sm抗体和抗核糖体P蛋白（r-RNP）抗体联检对系统性红斑狼疮（SLE）诊断的临床价值。方法：检测49例SLE患者、33例其他结缔组织病患者（对照组）和40名正常人血清ANA、抗ds-DNA抗体、抗Sm抗体和抗r-RNP抗体。结果：ANA、抗ds-DNA抗体、抗Sm抗体和抗r-RNP抗体在SLE患者中的阳性率明显高于对照组和正常人组（P〈0.01）;ANA与抗ds-DNA抗体的敏感性显著高于其他两种自身抗体（P〈0.05）;SLE活动期患者与非活动期患者抗ds-DNA抗体阳性率有显著性差别（P〈0.01）;抗ds-DNA抗体滴度与SLE-DAI呈正相关（r=0.57,P〈0.01）;ANA、抗ds-DNA抗体、抗Sm抗体和抗r-RNP抗体联检的敏感性可达98.0%。结论：自身抗体联检提高了SLE诊断的敏感性,对SLE的诊断和治疗有重要意义。     

CD134 expression on CD4+ T cells is associated with nephritis and disease activity in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by a deviation of the immune system that involves T cell-dependent autoantibody production. The aim of this study was to investigate the role of co-stimulatory markers on T cells in this disease. Twenty-eight patients with SLE as defined by the American College of Rheumatology (ACR) criteria and 11 healthy controls were included into the study. Eleven patients had biopsy-proven lupus nephritis while 17 patients had no clinical evidence of lupus nephritis. Clinical disease activity was assessed according to the systemic lupus erythematosus disease index (SLEDAI). CD4+ T cell populations in the peripheral blood were analysed for the expression of co-stimulatory markers CD45RO, CD70, CD80, CD86, CD137, CD137L, CD134, CD152, CD154 and ICOS. SLE patients showed an increased frequency of peripheral CD4+ T cells expressing high levels of CD80, CD86 and CD134 compared to healthy controls (7.1 +/- 1.5% versus 1.7 +/- 0.9%; P < 0.005; 2.3 +/- 0.4% versus 1.0 +/- 0.2%; P = 0.008, 20.2 +/- 2.0% versus 10.6 +/- 1.9%; P < 0.005, respectively). Significantly higher levels of CD80 on CD4+ T cells were detected in SLE patients with lupus nephritis compared to patients without nephritis (11.9 +/- 3.3% versus 4.0 +/- 0.7%; P < 0.005). There was an increased presence of CD134+ CD4+ cells in SLE patients with lupus nephritis (27.5 +/- 4.0% versus 15.5 +/- 1.3%; P < 0.005). CD80 and CD134 expression was significantly correlated with SLEDAI (r = 0.42, P = 0.03; r = 0.56, P < 0.005). Co-stimulatory molecules on CD4+ T cells are associated with renal disease and disease activity in patients with systemic lupus erythematosus.     

ANA negative (Ro) lupus erythematosus with multiple major organ involvement: a case report

Anti-nuclear antibody (ANA) negative systemic lupus erythematosus (SLE) occurs in about 4-13% of SLE cases. A small group of ANA negative SLE patients with positive anti-Ro antibodies usually present with typical vasculitic skin lesions which can be associated with photosensitivity, renal disease, congenital heart block or neonatal lupus. We present a case of a persistently ANA negative patient who presented with joint pain, rashes, mouth ulcer and alopecia. Clinical diagnosis of systemic lupus erythematosus was made even though ANA was negative. She was started on steroids and went into remission. Later, she developed several episodes of convulsions associated with fever and prominent vasculitic lesions. The patient was also found to have microscopic hematuria, proteinuria, anemia and thrombocytopenia. Renal biopsy showed lupus nephritis class 1B. Due to the prominent skin lesions, we performed anti-extractable nuclear antigens (ENA) antibodies test and anti-Ro turned out to be positive. The final diagnosis was ANA negative SLE (Ro lupus) with cutaneous, renal, musculoskeletal, hematological and cerebral Involvement.     

Association of angiotensin-converting enzyme polymorphisms with systemic lupus erythematosus and nephritis: analysis of 644 SLE families

Angiotensin II is a strong candidate for the perpetuation of autoimmunity, nephritis and visceral damage in systemic lupus erythematosus (SLE). Our goal was to determine whether angiotensin-converting enzyme (ACE) gene polymorphisms are associated with SLE and/or lupus nephritis (LN). We genotyped 644 SLE patients and 1130 family members for three ACE gene polymorphisms: Alu insertion/deletion (I/D), 23949 (CT)(2/3) and 10698 (G)(3/4). All patients met the American College of Rheumatology (ACR) criteria for SLE, and all LN patients met ACR renal criteria and/or had biopsy evidence of LN. We used the transmission/disequilibrium test (TDT) to examine associations between each polymorphism and SLE, including Caucasian, non-Caucasian, and LN subgroups. We also examined transmission of haplotypes defined by these polymorphisms. The ACE I/D polymorphism was associated with SLE among non-Caucasians (61% transmission, P = 0.026) and the 23949 (CT)(2/3) polymorphism was associated with LN among non-Caucasians (69% transmission, P = 0.014). Several haplotypes defined by these 2 markers demonstrated strikingly increased transmission among non-Caucasians (81% - 66% transmission, P = 0.0046 to 0.010). Due to the choice of study design and analytic method these results are unlikely to be due to population admixture. Our findings suggest that DNA sequence variation in the ACE gene influences the risk of developing SLE and LN.     

Anti-neutrophil Cytoplasmic Antibodies in New-onset Systemic Lupus Erythematosus and Lupus Nephritis

This study aims to investigate the role of Antineutrophil cytoplasmic antibodies (ANCA) in patients with new-onset systemic lupus erythematosus (SLE). Sixty SLE patients, 28 of whom had lupus nephritis (LN), and 60 normal controls were enrolled; Serum ANCA was measured by enzyme linked immunosorbent assay (ELISA). The clinical and laboratory parameters of the patients were also recorded. Results show that twenty SLE patients were seropositive for ANCA, which was significantly higher than in normal controls. LN patients had significantly higher positive rate of ANCA than patients without nephritis. Compared with ANCA-negative patients, the ANCA-positive patients had significantly higher incidence of nerves system disorder, myocarditis, renal involvement and serositis. The positive rate of gamma-globulin, anti-dsDNA and anti-Sm antibodies were significantly higher in ANCA-positive patients. Elevated IgG and ESR, decreased serum C3/C4 appeared more often in ANCA-positive patients. In addition, serum ANCA level correlated positively with disease activity. Taken together, ANCA might be used as a potential complementary parameter to differentiate LN from SLE without nephritis. In addition, ANCA may serve as a useful marker of the disease activity of SLE.     

Autoantibodies against monomeric C-reactive protein in sera from patients with lupus nephritis are associated with disease activity and renal tubulointerstitial lesions

Serum levels of C-reactive protein (CRP) often remain low despite high disease activity in systemic lupus erythematosus (SLE). Sera from 96 patients with renal biopsy-proven active lupus nephritis, 24 of 96 patients in remission, and 49 patients with SLE with negative urinalysis (nonrenal SLE) was collected. Immunoglobulin G autoantibodies against monomeric CRP (mCRP) were screened by enzyme-linked immunosorbent assay with purified human CRP. Associations with clinical features, pathological data, and laboratory findings were investigated. The prevalence of mCRP autoantibodies in active lupus nephritis (57/96, 59.4%) was significantly higher than that in patients with SLE without clinical evidence of kidney involvement (20/49, 40.8%, p = 0.034). For the 13 patients with positive mCRP autoantibodies and sequential sera, their positive mCRP autoantibodies in active phase turned negative in remission (13/13, 100%). Patients with mCRP autoantibodies had significantly higher SLEDAI scores than patients without mCRP autoantibodies (18.3 +/- 5.2 vs 15.8 +/- 4.0, p = 0.013), who were more likely to experience acute renal failure (14/55 vs 2/33, p = 0.022), oral ulcer (15/57 vs 3/39, p = 0.022), and delayed activated partial thromboplastin time (18/52 vs 2/38, p = 0.001). Positive correlations between levels of mCRP autoantibodies and semiquantitative scores of renal histologic features were first observed in lupus nephritis as follows: interstitial inflammation (r = 0.328), tubular atrophy(r = 0.276), interstitial fibrosis (r = 0.211), and chronicity index score (r = 0.243). Autoantibodies against mCRP are prevalent in patients with lupus nephritis and are associated with disease activity and renal tubulointerstitial lesions.     

TLR4介导高迁移率族蛋白致系统性红斑狼疮肾损害的作用研究

目的 探讨高迁移率族蛋白1(HMGB1)致红斑性狼疮肾损害的作用机制与Toll样受体4(Toll-like receptor 4,TLR4)表达的相关性.方法 ELISA检测12例健康对照组、16例系统性红斑狼疮(systemic lupus eqrthematosus,SLE)无肾脏损害和18例狼疮性肾炎(lupus nephritis,LN)患者血清中HMGB1、基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶组织抑制剂-2(TIMP-2)的表达情况;流式细胞术检测外周血CD3/TLR4和CD14/TLR4表达情况;分离外周血单个核细胞(PBMC),RT-PCR检测HMGB1 mRNA的表达变化.结果 HMGB1 mRNA相对表达量及血清中HMGB1蛋白在LN组明显高于SLE组和健康对照组;流式细胞术显示CD14+的单核细胞表面HMGB1受体TLR4在LN组表达最高(P＜0.05),且与尿蛋白呈正相关(P＜0.01);LN患者血清中MMP-2和TIMP-2蛋白的浓度明显低于SLE和健康对照组,同时MMP-2/TIMP-2比值下降.HMGB1 mRNA及CD14+/TLR4+与MMP-2/TIMP-2比值均呈显著负相关;LN组患者血清中HMGB1蛋白水平与蛋白尿呈正相关,与MMP-2/TIMP-2比值呈显著负相关.结论 HMGB1是狼疮性肾炎发病中的重要细胞因子;HMGB1可能部分通过TLR4激活PBMC,降低MMP-2/TIMP-2的活性,从而引起蛋白尿.