The significance of anti-endothelial cell antibodies in patients with lupus nephritis and immunoblotting analysis of the target components

ＯｂｊｅｃｔｉｖｅＴｏｉｎｖｅｓｔｉｇａｔｅｔｈｅｐｒｅｖａｌｅｎｃｅｏｆａｎｔｉｅｎｄｏｔｈｅｌｉａｌｃｅｌａｎｔｉｂｏｄｉｅｓａｎｄｉｔｓｐｏｓｓｉｂｌｅｒｏｌｅｉｎｔｈｅｐａｔｈｏｇｅｎｅｓｉｓｉｎｌｕｐｕｓｎｅｐｈｒｉｔｉｓＭｅｔｈｏｄｓ...     

抗心磷脂抗体及抗核抗体与反复自然流产的关系

目的：探讨抗心磷脂抗体（ACA）及抗核抗体（ANA）与反复自然流产（RSA）的关系。 方法：采用ELISA法检测98例RSA患者及40例正常妇女血清ACA和ANA。 结果：RSA组ACA阳性率为32.7%,明显高于对照组（5.0%,P<0.01）;早期与晚期RSA两组间比较,ACA阳性率差异无显著性（P>0.05）,RSA 2次与RSA≥3次两组间比较,ACA阳性率差异无显著性（P>0.05）;ACA IgM、IgG、IgA中以IgG、IgM检出率较高,ACA IgM、IgG、IgA同时阳性者仅4例;阳性和强阳性ACA占37.5%(11/32),其余均为ACA弱阳性;RSA患者ANA阳性率为17.3%,较对照组（2.5%）明显增高（P<0.05）。 结论：ACA及ANA与RSA有关,可作为RSA免疫因素的辅助诊断指标。     

狼疮性肾炎抗活化蛋白C的测定及意义

目的 :探讨抗磷脂抗体和抗活化蛋白C(APCR)与狼疮性肾炎 (LN)的关系及APCR的可能形成原因。方法 :检测 33例LN和 37例无LN的系统性红班狼疮 (NLN) ,ELISA检测ACA -IgG、IgM、IgA、PTT -LA检测LA ,APTT±APC检测APCR。结果 :LN组APCR阳性率 5 7 6% ,明显高于NLN组 ( 32 4% ) ;LN组ACA(IgG、IgM )阳性率 42 4% ,明显高于NLN组 ( 18 9% ) ;APCR和IgG -ACA同时阳性LN的发生率 ( 7/ 7)明显高于APCR阳性而IgG -ACA阴性者( 12 / 2 4)。结论 :APCR和ACA在LN有较高的发生率 ,ACA引起的获得性APCR可能是LN的发病机制之一。     

白芍总苷对MRL/lpr小鼠狼疮性肾炎的影响

目的观察白芍总苷(TGP)对MRL/lpr小鼠狼疮性肾炎的影响。方法将MRL/lpr狼疮肾炎小鼠随机分为模型组和TGP组。考马斯亮蓝法检测尿蛋白含量,酶联免疫吸附法(ELISA)检测血清IgG型抗dsDNA抗体、ANA水平,HE染色光镜下观察肾组织病理改变,称脾脏和胸腺湿重,并计算脾脏和胸腺指数。结果①与模型组相比,TGP组用药后15、30 d尿蛋白含量显著下降(P<0.05),用药后30 d抗dsDNA抗体、ANA水平和脾脏质量及其指数均显著下降(P<0.05),肾脏组织病理损害明显减轻。②TGP组用药后15、30 d与用药前相比,尿蛋白含量、抗dsDNA抗体水平、ANA水平显著下降(P<0.05),而模型组抗dsDNA抗体水平显著上升(P<0.05),尿蛋白含量、ANA水平无显著差异;TGP组用药后30d与用药后15d相比尿蛋白含量显著下降(P<0.05),抗体水平无显著差异。结论白芍总苷可以降低尿蛋白含量和血清抗dsDNA抗体、ANA水平,明显改善肾组织病理损害,对MRL/lpr小鼠狼疮性肾炎具有一定疗效。     

系统性红斑狼疮相关实验室检查结果分析

目的　通过对系统性红斑狼疮 (SLE)患者实验室检查结果的分析来探讨临床早期诊断的指标。方法　回顾性对 57例SLE患者的血液学特别是ANA ,抗ds-DNA及ENA谱测定结果与正常对照组进行分析。结果　SLE贫血最常见占 73 .7%。ANA阳性占96 .5 % ,抗ds -DNA阳性占 57.9% ,ENA阳性占 66 .7%。而正常对照组均为 0 % (P <0 .0 1 )。结论　血液学及几种自身抗体检测异常对该病早期诊断及鉴别诊断 ,病情监测 ,疗效观察有重要意义     

抗心磷脂抗体在神经精神性狼疮中的临床研究

目的探讨抗心磷脂抗体在神经精神性狼疮中的意义。方法采用ELISA方法，检测93份血清（包括NPLE患者33例，无神经精神症状的狼疮患者35例，非SLE所致脑血管意外患者25例）和17例脑脊液（包括NPLE患者6例，无神经精神症状的狼疮患者5例，非SLE所致脑血管意外患者6例）中的抗心磷脂抗体。结果血清中抗心磷脂抗体（ACA）IgG、IgM阳性率分别为59．1％、57％，其中33例神经精神性狼疮患者阳性率为90．9％，87．9％，35例无神经精神症状的狼疮患者阳性率为34．3％，25例非系统性红斑狼疮脑血管意外患者阳性率为52％，48％各组之间有显著差异（P〈0．005）。NPLE患者组与无神经精神症状的狼疮患者组及非系统性红斑狼疮脑血管意外患者组之间均有显著差异（P〈0．05）。脑脊液中ACA—IgG、ACA—IgM阳性率分别为6／17、5／17，NPLE患者组与无神经精神症状的狼疮患者组及非系统性红斑狼疮脑血管意外患者组之间均无显著差异（P〉0．05）。33例NPLE患者，血清ACA—IgG、IgM检测、认为、弥漫性表现患者与局灶性表现患者比较，血清ACA、抗体水平不同，局灶性表现患者升高较明显（P〈0．05）。结论血清中ACA与NPLE密切相关。     

CLINICAL SIGNIFICANCE OF COMBINED ANTINUCLEAR AND ANTICYTOPLASMIC ANTIBODIES DETECTED BY IMMUNOFLUORESCENCE

Anti-nuclear antibodies (ANA) combined with anti-cytoplasmic antibodies (ACA) in 0.6% (n = 43) of 7,121 consecutive patients referred for ANA screening were observed. Homogeneous/cytoplasmic was the most frequently combined ANA/ACA pattern among 6 different indirect immunofluorescent (IF) combinations. Distribution of diseases was similar in patients with ANA/ACA and those controls with ANA alone. However, the ANA/ACA results were often transitory, especially in systemic lupus erythromatosus (SLE). The appearance of transitory ANA/ACA combinations on serial ANA testing may be useful as a serologic marker for SLE.     

狼疮性肾炎患者抗心磷脂抗体的测定及其临床意义

目的：为探讨抗心磷脂抗体(Anticardiolipin antibodies—ACA)在狼疮性肾炎(LN)中的临床意义。方法：采用ELISA法检测32例LN4患和28例健康对照组血清ACA的水平，并观察ACA水平与LN患有关临床生化指标的相互关系。结果：在LN患中，IgG—ACA、IgM—ACA和IgA—ACA阳性率分别为53．1％、40、6％和46、9％。ACA阳性患中，血红蛋白及血小板减少，C3水平降低；血清IgG水平、ANA滴度水平，24 h尿蛋白定量及血肌酐水平均增高(P＜0．05)。结论：ACA阳性可能与LN患存在更为严重的免疫功能紊乱，高凝状态和更严重的肾脏损害有密切的关系。     

Inhibitory oligodeoxynucleotide improves glomerulonephritis and prolongs survival in MRL-lpr/lpr mice

Inhibitory oligodeoxynucleotides (ODNs), which are capable of blocking CpG-induced inflammation, have been anticipated to be beneficial therapeutic agents for autoimmune diseases. In this study, we show that GpC ODN, which inverted the cytosine guanine sequence of CpG motif to guanine cytosine sequence, is an inhibitory ODN. The inhibitory effects of GpC ODN on CpG ODN-induced immune activation were confirmed by cytokine assay using splenocytes from lupus-prone MRL-lpr/lpr mice. In vivo, injecting MRL-lpr/lpr mice with GpC ODN did not reduce the deposition of IgG and C3 in the glomeruli, the serum level of IL-12, the serum level of rheumatoid factors and anti-ds DNA antibody, or alter the composition of IgG isotypes of anti-ds DNA antibody. However, the mice in the GpC group showed less proteinuria, significantly lower blood urea nitrogen levels (BUN) and significantly prolonged survival. Our results suggest that inhibitory ODNs, such as GpC ODN, have the potential to become a treatment for autoimmune diseases, like lupus nephritis.     

系统性红斑狼疮抗核抗体及其变化的临床意义

目的探讨抗核抗体及其变化在系统性红斑狼疮（SLE）的临床意义。方法对50例SLE患者的实验室及临床资料进行回顾性分析。结果IFANA、抗ds—DNA、抗Sm、抗U1-RNP、抗SS—A、抗SS—B抗体的阳性率分别为100％、70％、30％、44％、52％、22％。IFANA的滴度高低与病情活动状况无关，转阴并不表示病情缓解；抗ds—DNA抗体与狼疮性肾炎相关，持续高滴度常表示疾病活动特别是狼疮肾活动；抗SM抗体与病情无关，治疗后易消失；抗U1-RNP抗体与雷诺氏现象相关；抗SS—A抗体与光敏感相关；抗SS—B抗体与干燥综合征相关。抗U1-RNP抗体、抗SS—A抗体及抗SS—B抗体这3种抗体多持续存在。结论在SLE，各种ANA可能代表不同的亚型。     

系统性红斑狼疮患者血清抗亲环素A抗体检测的临床意义

目的：观察血清抗亲环素(CyP)A抗体对系统性红斑狼疮(SLE)的诊断价值与临床意义。方法：用ELISA方法检测54例SLE、36例其他自身免疫病患者及40例健康对照者血清IgG、3种抗CyP A抗体并结合活动性评分、系统损害进行分析。结果：54例SLE患者中23例检出IgG型抗CyP A抗体，15例IgM型、3例IgA型抗CyP A抗体。IgG型抗CyP A抗体的灵敏度为42．6％，特异性为55．6％，IgM型CyP抗体的灵敏度为27．8％，特异性为36，1％。SLE三重度活动组两型抗CyP A抗体检出率高于稳定期及轻、中度活动组。IgG型及IgM型抗体与血中低补体及免疫球蛋白升高有关，IgG型抗CyP A抗体与SLE关节肌肉症状及白细胞减少有关。结论：IgG型抗CyP A抗体检出的临床价值优于IgM型抗体。CyP A抗体非SLE三特异性抗体，但可作为判断SLE病情活动性的参考指标之一。     

Induction of anti-DNA antibodies by immunization with activated lymphocytes and active chromatin

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反复流产和不孕症与支原体和免疫因素的关系

目的 :探讨反复自发性流产 (RSA)与支原体感染和抗心磷脂抗体 (ACA)之间的关系及不孕症与支原体感染和抗精子抗体 (ASA)之间的关系 .方法 :采用培养法分别对 338例RSA患者 (观察组 )和 2 4 8例不孕症患者 (观察组 )进行解脲支原体 (UU)和人型支原体 (MH)检测 ;采用ELISA法分别检测血清ACA IgM和ACA IgG(RSA观察组 )以及ASA IgM和ASA IgG(不孕症观察组 ) .同时分别选择 1 0 5例正常妇女作为对照组 .比较观察组和对照组各项指标阳性检出率 .结果 :RSA患者和不孕症患者支原体感染阳性率均高于对照组(P <0 .0 5 ) ;RSA患者血清ACA IgM阳性检出率明显高于对照组 (P <0 .0 5 ) ;不孕症观察组ASA IgM阳性检出率均显著高于对照组 (P <0 .0 5 ) ;RSA患者中 ,支原体感染阳性组ACA IgM ,ACA IgG以及ACA IgM +ACA IgG阳性率均明显高于支原体感染阴性组 (P <0 .0 5 ) ;不孕症患者中 ,支原体感染阳性组ASA IgM和ASA IgGA阳性率均明显高于支原体感染阴性组 (P <0 .0 5 ) .结论 :支原体感染是RSA和不孕症的原因之一 ;自身免疫性抗体与RSA和不孕症有一定关系 ;ACA和ASA均与支原体感染有相关性     

80例狼疮肾炎病人ANA荧光核型及抗核抗体谱分析

目的探讨抗核抗体（ANA）荧光核型及抗核抗体谱多肽谱对狼疮性肾炎（LN）诊断的有效指标。方法对80例LN组、78例系统性红斑狼疮（SLE）非LN组及104例非SLE组分别用间接荧光法（IIF—ANA）和线性免疫印迹法（uA—ANA）进行抗核抗体荧光核型、双链DNA及11项抗核抗体谱多肽谱分析。结果LN组抗核抗体阳性率（〉1：100）为100％（80／80）,LN组荧光核型均质型42．5％（34／80）显著高于非IN组21．79％（17／78）与对照组5．77％（6／104）,P〈0．05;LN组颗粒核型53．75％（43／80）明显低于非LN组73．08％（57／78）,P〈0．05。LN病例核均质型主要表现有抗Hi、Nud、dsDNA抗体,x2为8．26、23．05、26．39（e均〈0．05）。抗核抗体谱多肽谱分析,LJN组仅抗dsDNA抗体55．0I）％（44／80）高于非LN组23．08％（18／78）,差异有显著性,P〈0．C15。结论SLE伴狼疮性肾炎的病人ANA荧光核型主要表现为均质型,抗dsDNA抗体阳性率显著性增高,可视为预测狼疮性肾炎的有效指标。     

The occurrence of autoantibodies in sera of healthy pregnant women

Autoantibodies have been known to be detected during pregnancy. The occurrence of autoantibodies during pregnancy was studied in a group of 146 healthy pregnant women from Jan-March 1995. Serum samples were tested for antinuclear (ANA), anti-ds DNA, anti-mitochondrial, anti-smooth muscle and anti-parietal cell antibodies employing the technique of indirect immunofluorescence. Sera from 66 non-pregnant women were used as controls. Among the pregnant group, 2 (1.4%) were found to have ANA positivity in comparison to none in the control group. This difference was found to be not statistically significant. Only 1 (0.7%) was positive for anti-mitochondrial antibody in the pregnant group compared to one in the control group (p > 0.05). However, anti-ds DNA, anti-smooth muscle and anti-parietal cell antibodies were not detected in both groups. All those positive for autoantibodies were in their 2nd trimester. When these cases were followed-up at the end of their pregnancy, none had complicated pregnancies nor infant abnormalities. Our findings suggest that (a) the occurrence of autoantibodies in pregnant women was not significantly different from non-pregnant controls and that (b) maternal autoantibodies did not appear to cause complications during pregnancy or infant morbidity.     

利用Sm抗原模拟表位肽构建狼疮样鼠模型

目的利用Sm抗原模拟表位肽免疫BALB/C小鼠,构建狼疮样鼠模型。方法用鼠Sm单克隆抗体对噬菌体随机12肽库进行亲和筛选,将筛选的噬菌体阳性克隆行双抗体夹心ELISA检测、DNA序列测定并推导其氨基酸序列,初步确定Sm抗原模拟表位;进而用混合噬菌体阳性克隆皮下免疫BALB/C小鼠,ELISA法检测小鼠血清IgG型抗Sm抗体、抗双链DNA（dsDNA）抗体和抗核抗体（ANA）水平;直接免疫荧光检测小鼠肾脏IgG型免疫复合物的沉积以及HE染色观察小鼠肾脏组织病理损伤情况。结果免疫筛选获得的5个ELISA强阳性的噬菌体克隆的氨基酸序列IR、SQ、PP出现频率增加;实验组小鼠血清中第28天出现Sm抗体、dsDNA抗体、ANA抗体,且滴度不断升高;第33天出现蛋白尿;肾脏可以检测到IgG型免疫复合物沉积及明显的肾脏病理改变。对照组小鼠无明显自身抗体产生和肾脏病变。结论利用Sm抗原噬菌体模拟表位肽可成功构建狼疮样小鼠模型。     

抗着丝点抗体与抗核抗体在原发性胆汁性肝硬化的临床意义

目的探讨抗着丝点抗体(ACA)在原发性胆汁性肝硬化(PBC)中的临床意义。方法收集67例抗线粒体抗体(AMA)和AMA-M2阳性PBC患者的临床资料,检测其抗核抗体(ANA)和ACA、生化、凝血酶原活动度(PT)及免疫指标等。结果 ACA阳性组27例,ACA和ANA均阴性组40例。ACA阳性组脾肿大的发生率高于ACA和ANA阴性组(77.8% vs. 40.0%,P=0.002)。ACA阳性组黄疸的发生率、血清总胆红素(TBIL)水平、IgG水平和IgG异常升高率明显低于ACA和ANA阴性组[25.9% vs. 55.0%,P=0.018;(41.62±45.96)μmol/L vs. (88.49±99.13)μmol/L,P=0.012;(13.90±2.75)g/L vs. (18.32±6.34)g/L,P=0.002;29.4% vs. 60.0%,P=0.044]。两组在其他临床表现、肝功能及其他免疫指标的差异无统计学意义。结论单一ACA阳性PBC患者疾病的进展比ACA和ANA阴性患者更加隐匿。ACA阳性PBC患者是PBC的一个特殊类型。     

The relationship between lupus anticoagulants and antibodies to phospholipid

The relationship between lupus anticoagulants and antibodies directed against negatively charged phospholipids, as measured by an enzyme-linked immunosorbent assay, was explored in a series of plasma samples from 100 patients with well-characterized lupus anticoagulants. Only 73% of the patients had detectable IgG, IgM antibodies, or both, to one or more of four phospholipids. Of these patients, 29% had IgG-type antibodies only, 56% had both IgG and IgM antibodies, and 15% had IgM antibodies only. Of the 100 patients, 19% had a history of thrombosis, 8% had a history of spontaneous abortion, and 6% had a history of seizure disorder. These complications occurred in the presence (80%) and absence (20%) of detectable antiphospholipid antibodies. Drug-related antibodies were observed in 34 patients; of these, 71% had detectable anti-phospholipid antibodies and 24% had a history of thrombosis. There were ten patients with lupus anticoagulants associated with infections; none of these patients had a history of thrombosis. The results indicate that antiphospholipid antibodies are not present in all patients with lupus anticoagulants, that the presence of antiphospholipid antibodies in patients with lupus anticoagulants does not increase the risk of thrombosis in these patients, and that drug-related antibodies are associated with an increased risk of thrombosis. Lupus anticoagulants and antiphospholipid antibodies seem to define two distinct but related patient populations, each associated with an increased risk of thrombosis.     

AnA、AnuA、抗Sm抗体、抗dsDNA抗体测定在诊断SLE中的作用

目的：通过检测抗核抗体（AnA）、抗核小体抗体（AnuA）、抗Sm抗体、抗dsDNA抗体,探讨它们在系统性红斑狼疮（SLE）中的诊断价值。方法：检测120例SLE患者中的AnA、AnuA、抗Sm抗体、抗dsDNA抗体水平,AnuA采用ELISA法测定,抗Sm抗体采用免疫斑点法测定,抗dsDNA抗体及AnA采用间接荧光免疫法测定。结果：在检测的120例SLE患者中,AnA、AnuA、抗Sm抗体、抗dsDNA抗体的阳性率分别为97.5%、85.0%、42.5%、45.0%,在结缔组织中的阳性率分别为77.6%、1.0%、2.0%、3.0%。健康对照组中的阳性率分别为15.0%、0、0、1.0%。AnA、AnuA、抗Sm抗体、抗dsDNA抗体的检测对SLE患者的诊断特异性分别为22.4%、99.0%、98.0%、96.9%。结论：AnuA对SLE患者的诊断特异性最高;AnA对SLE诊断的阳性率最高,但其特异性最低,AnuA、抗Sm抗体、抗dsDNA抗体测定都可作为SLE诊断的可靠指标。     

狼疮样肾炎小鼠模型的建立及评价

系统性红斑狼疮(Systemic lupus erythematosus,SLE)是一种以体内产生抗核抗体为特征的自身免疫性疾病,其病因目前未明,一般认为是遗传、环境、内分泌、感染等因素相互作用的结果。狼疮样肾炎小鼠模型与人SLE发病机制和病理变化等有着相似特点,是研究SLE、筛选抗炎免疫药物较理想的实验性病理模型。本文对近年来狼疮样肾炎小鼠模型制备的方法及评价进行了综述。