抗心磷脂抗体在狼疮肾炎患者中的临床意义

背景:以往的研究表明,在系统性红斑狼疮及抗磷脂抗体综合征患者中,升高的抗心磷脂抗体滴度与血管血栓形成、血小板减少及反复流产的发生明显相关.但有关抗心磷脂在狼疮性肾炎患者中的临床意义的研究报道却不完全统一.目的:探讨抗心磷脂抗体在中国狼疮性肾炎患者中的阳性率及临床意义.设计:前瞻性单一样本的随访观察.单位:深圳市第四人民医院香蜜湖风湿病分院,广东医学院深圳风湿病研究所.对象:选择2001-03/2003-10于深圳市第四医院香蜜湖风湿病分院风湿科门诊就诊或住院的狼疮性肾炎患者97例.均符合美国风湿病学学会(ACR).1997年修订的狼疮性肾炎的诊断和分类标准.纳入对象均对检测项目知情同意.方法:记录患者入院后的临床资料和辅助检查结果.应用酶联免疫吸收法检测患者血清中的抗心磷脂抗体,阳性判断标准为测定值超过100 U/mL.大剂量口服强的松联合环磷酰胺静脉冲击治疗以诱导缓解,然后逐渐将强的松减量,将环磷酰胺换成硫唑嘌呤以维持疗效.同时使用其它药物控制可能合并的高血压、高血脂与关节痛等症状.每半年对纳入对象进行定期随访,记录狼疮性肾炎患者的临床资料及实验室检查结果,共3年.主要观察指标:患者的性别、年龄、系统性红斑狼疮病情活动指数,血栓形成、病理妊娠等临床表现及肾功能等实验室检查结果.结果:实验共纳入狼疮性肾炎患者97例,83例进入结果分析,14例脱落.在入选的97例患者中,其发病后被确诊时抗心磷脂抗体阳性者有38例(39%),高血压,血小板减少及雷诺现象在伴有抗心磷脂抗体阳性的狼疮性肾炎患者中更为常见.IgG型抗心磷脂抗体阳性狼疮件肾炎患者更易发生血管血栓形成:抗心磷脂抗体阳性狼疮性.肾炎患者更易发生流产、早产和死胎以及慢性肾功能不全恶化.结论:抗心磷脂抗体在狼疮性肾炎患者中的阳性率为39%,抗心磷脂抗体阳性的患者更易出现高血压,血小板减少及雷诺现象,抗心磷脂抗体阳件对预测狼疮性肾炎出现血管血栓形成、病理妊娠及慢性肾功能不全恶化可能有一定作用.     

抗心磷脂抗体与狼疮性肾炎患者肾功能的关系

目的探讨狼疮性肾炎患者抗心磷脂抗体(ACA)对肾功能的影响。方法对68例狼疮性肾炎患者随访1年,测定其血清ACA及肾功能。结果狼疮性肾炎肾功能正常组和肾功能不全组的IgG鄄ACA、IgA鄄ACA、IgM鄄ACA阳性率分别为40.5%、35.7%、40.5%(P<0.01)及57.7%、38.5%、46.2%(IgG,P<0.01;IgA,IgM,P<0.05),与对照组相比差异有显著性。随访期ACA阳性组肾功能不全者明显超过ACA阴性组(P<0.05),随着ACA转阴,肾功能逐渐恢复。结论ACA与狼疮性肾炎的肾功能损害密切相关,应用泼尼松和环磷酰胺降低血清ACA滴度,肾功能损害也随之好转。     

抗心磷脂抗体在狼疮性肾炎中的临床意义

应用ＥＬＩＳＡ法测定狼疮性肾炎，原发性肾小球肾炎患者及正常人血清中ＡＣＡ，结果表明狼疮性肾炎组ＡＣＡ阳性率明显高于其它组（Ｐ＜０．０５），且狼疮性肾炎患者的血小板下降，血红蛋白减少，补体Ｃ３降低及肌酸磷酸激酶活性降低与ＡＣＡ有明显关系。     

系统性红斑狼疮患者抗磷脂抗体与视网膜血管病关系的研究

目的：研究系统性红斑狼疮(systemic lupus erythematosus，SLE)抗磷脂抗体等血清免疫学标志物与患视网膜血管病的关系。方法：从2002年6月至2003年1月，对164例SLE患作最佳矫正视力检查、眼压测量、裂隙灯检查和眼底检查，血清免疫学检查指标包括抗心磷脂抗体(anticardiolipin antibody,ACL、狼疮抗凝物(lupus anticoagulant,LA)、抗核抗体(antinuclear antibody，ANA)和抗ds—DNA抗体等。结果：164例SLE患中26例(16则检查到有视网膜血管病，其中19例(73%)检测到抗磷脂抗体(17例ACL和2例LA)。结论：SLE患易发生视网膜血管病变，抗磷脂抗体的存在可能与其有较高的相关性。     

抗磷脂抗体与抗磷脂血栓综合征

抗磷脂抗体（ＡＰＡ）与抗磷脂血栓综合征（ＡＰＬ－Ｔ）的发生密切相关,但ＡＰＡ引起ＡＰＴ－Ｔ的发病机制仍不清楚,近年来ＡＰＡ通过抑制蛋白Ｃ（ＰＣ）途径,引起获得抗活化蛋白Ｃ现象进而导致血栓的研究受到关注。本主要将抗磷脂血栓综合征的研究进展作一综述。     

狼疮肾炎抗中性粒细胞胞浆抗体与临床表现的相关性研究

【目的】探讨系统性红斑狼疮肾炎（LN）患者抗中性粒细胞胞浆抗体（ANCA）水平及与其他临床表现的相关性。【方法】选取40例LN患者和23例非LN患者。用间接免疫荧光法（ⅡF）检测患者血清AN—CA（荧光位于胞浆为c—ANCA）；位于核周p—ANCA；经典型为a-ANCA；ELISA法检测ANCA抗原（包括抗-MPO，抗-LF，抗-CG）。【结果】40例LN患者中，19例（47．5％）ANCA阳性，其中p—ANCA阳性者17例（89．5％），2例（10．5％）为a—ANCA。无一例出现c—ANCA。在LN组，p-ANCA滴度为（1：80）（1：160），滴度最高者为弥漫性增生性肾小球肾炎（DPGN）；2例a—ANCA均出现在急进性肾小球肾炎（RPGN）。非LN组23例患者中，仅3例（13％）p-ANCA阳性，滴度为1：80，且均为抗-MPO。正常对照组无一例ANCA阳性。63例系统性红斑狼疮（SLE）患者中，11例（17．5％）为抗-MPO；10例（15．9％）为抗一LF，且只见于DPGN、局灶增殖性肾小球肾炎（FPGN）和RPGN伴有新月体形成者；8例（12．7％）为抗-CG，但在LN患者未检测到抗-LF及抗-CG。在各种临床表现中，抗-MPO与肾脏和皮肤表现有关；而抗-LF与肾脏、关节炎及浆膜炎有关；抗-CG可见于各种临床表现。【结论】ANCA可能与狼疮肾炎有关，且抗-MPO与其关系最明显。     

抗磷脂抗体与抗磷脂血栓综合征

抗磷脂抗体(APA)与抗磷脂血栓综合征(APL-T)的发生密切相关,但APA引起APL-T的发病机制仍不清楚,近年来APA通过抑制蛋白C(PC)途径,引起获得性抗活化蛋白C现象进而导致血栓的研究受到关注。本文主要将抗磷脂血栓综合征的研究进展作一综述。     

不同抗核抗体滴度狼疮肾炎患者血清补体及其他指标研究

目的探讨不同抗核抗体(ANA)滴度的狼疮肾炎(LN)患者血清补体、血脂、肝肾功能的变化,为临床诊断、监测及预防疾病提供有价值的辅助性指标。方法收集武汉大学人民医院皮肤科与肾病内科住院患者318例,其中系统性红斑狼疮(SLE)组患者133例,LN组患者185例。对照组为同期来该院体检健康者共103例。肝功能指标、肾脏指标及血脂指标检测均采用Siemens公司生产的全自动生化分析仪Advia 2400。补体C3与C4检测均采用贝克曼公司生产的全自动分析仪IMMAGE800。结果肝脏指标丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)与直接胆红素(DBIL),肾脏指标尿素(Urea)、肌酐(Cr)、尿酸(UA),血脂指标低密度脂蛋白(LDL)、总胆固醇(TCH)、三酰甘油(TG),以及补体在LN、SLE患者与健康人群之间进行比较,差异有统计学意义(F_(ALT)=7.42,F_(AST)=4.54,F_(DBIL)=26.70,F_(TBIL)=15.01,F_(Cr)=40.52,F_(UA)=82.60,F_(Urea)=48.03,F_(LDL)=10.73,F_(TCH)=8.13,F_(TG)=32.61,F_(C3)=39.75,F_(C4)=36.24,P0.05)。但是高密度脂蛋白(HDL)在3组间比较,差异无统计学意义(F_(HDL)=2.25,P0.05)。肝功能、肾功能、血脂及补体指标在不同ANA滴度的LN患者间比较,仅发现肾功能Cr指标在不同ANA滴度的LN患者间比较,差异有统计学意义(FCr=4.569,P0.05),补体指标在不同ANA滴度的LN患者间比较,差异有统计学意义(F_(C3)=8.127,F_(C4)=5.351,P0.05)。经线性回归并采用逐步回归方法分析后发现补体C3(t=-5.062,P0.05)、Cr(t=-3.791,P0.05)与ANA滴度具有独立线性相关。结论 LN患者的ANA滴度与补体C3、Cr具有独立线性相关性,并且呈负相关,可作为LN患者疾病病程进展的辅助诊断指标。     

抗心磷脂抗体检测和抗磷脂抗体综合征诊断

磷脂是指分子中含有醇 ,脂肪酸和磷酸基团的一类化合物。人体内的磷脂主要是含有甘油醇的甘油磷脂 ,包括心磷脂 ,磷脂酰丝氨酸 ,磷脂酰胆固醇 ,磷脂酰乙醇胺等。抗磷脂抗体 (antiphospholipidantibody ,aPL)是一族针对带负电荷磷脂或带负电荷磷脂与蛋白复合物的异质性抗体。抗磷脂抗体综合征 (antiphospholipidsyndrome ,APS) ,是一组与抗磷脂抗体有关的自身免疫性疾病 ,典型的临床表现有动脉血栓 ,静脉血栓以及妊娠丢失。APS患者血中检出aPL是确立APS诊断的必要条件。根据一些aPL可以识别磷脂或磷脂与蛋白复合物的特性 ,采用心磷脂包…     

抗磷脂抗体与血栓形成

抗磷脂抗体（包括狼疮样抗凝物及抗心磷脂抗体）是多种原因诱发的异质性自身抗体，进一步的研究表明抗磷脂抗体与血栓形成密切相关，检测抗磷脂抗体对临床医师预测，诊治血栓病具有一定的指导意义，本文综述了抗磷脂抗体的分类，与血栓形成的关系及检测方法，防治措施。     

狼疮肾炎尿毒症治疗中两种透析法的疗效比较

目的：探讨在腹膜透析（腹透）或血液透析（血透）辅助治疗下激素和细胞毒性药物（环磷酰胺）对狼疮肾炎（ＬＮ）尿毒症的逆转作用。方法：观察ＬＮ尿毒症患者腹透组（３７例）与血透组（１５例）在透析治疗尿毒症症状消失后，予以相同剂量和用法的泼尼松与环磷酰胺治疗的疗效，并进行比较。结果：腹透组３７例中，３１例（８３．８％）成功脱离了透析，６例（１６．２％）无效，但可以减少每周透析次数；而血透组１５例中仅４例（２６．７％）脱离了透析，１１例（７３．３％）无效，其中１例可以减少每周透析次数，１０例仍需继续作维持性血透。２组疗效有极显著性差异（Ｐ＜０．０１）。结论：ＬＮ尿毒症应尽可能选择腹透作辅助治疗。     

Migraine and antiphospholipid antibodies

Antiphospholipid antibodies have been detected in patients with transient neurologic symptoms including migraine aura. The role of these antibodies in the pathogenesis of migraine is not fully understood. The available data suggest an association between the migraine-like phenomena and antiphospholipid antibodies, but not between migraine headache and antiphospholipid antibodies. To elucidate the actual role of antiphospholipid antibodies in migraine, prospective, controlled studies are needed.     

Increased thromboxane formation in patients with antiphospholipid syndrome

Thirty-one patients with IgG antibodies to cardiolipin (ACLA) were studied to determine their in vivo formation of the platelet aggregating and vasoconstricting substance thromboxane A2 (TxA2) and the platelet inhibiting and vasodilating substance prostacyclin (PGI2). This was done by measurements in urine of their enzymatically formed metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha, respectively, using gas chromatography-mass spectrometry. It is demonstrated that patients with IgG ACLA have a highly significant increase in the biosynthesis of TxA2 compared with age-matched healthy controls (807 +/- 163 [SEM] vs. 230 +/- 15 pg mg-1 creatinine, P = 0.0000005). A significant increment of the formation of PGI2 was also found (189 +/- 23 (SEM) vs. 125 +/- 11 pg mg-1 creatinine, P = 0.03), although this was much less pronounced than that for TxA2. We conclude that the highly increased formation of TxA2, reflecting platelet activation, in patients with IgG ACLA is of pathophysiologic relevance for their tendency to arterial and venous thrombosis and hence that they should be considered for prophylactic treatment with inhibitors of TxA2 formation, like aspirin.     

False-positive tests for heparin-induced thrombocytopenia in patients with antiphospholipid syndrome and systemic lupus erythematosus

Summary.  Background : Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy that can be associated with arterial or venous thrombosis and is caused by antibodies against platelet factor 4 (PF4)–heparin complex. Patients with antiphospholipid syndrome (APS) have been reported with positive tests for PF4–heparin complex antibodies by antigen assay. Whether such patients can be treated with heparin is a dilemma. Objectives : To determine the incidence and nature of the HIT immune reaction in patients with APS and/or systemic lupus erythematosus (SLE). Methods : Antibodies against PF4–heparin complex were assayed by particle gel immunoassay (PaGIA), or enzyme immunoassay (EIA) with or without an excess of heparin. EIA for PF4 alone was also performed. Functional assays for HIT, that is, heparin-induced platelet activation (HIPA) and heparin-induced platelet aggregation, were also performed. Results : In 32 of 42 patients (76.2%) with APS, APS and SLE, SLE, or SLE with antiphospholipid antibodies, EIA IgG or PaGIA for PF4–heparin complex antibodies were positive. Of these 32 samples, 26 (81.3%) tested positive for anti-PF4 antibodies. All 24 samples that were positive for PF4–heparin complex by EIA IgG were also positive for EIA IgG in the presence of heparin excess, and all were negative by the HIPA and heparin-induced platelet aggregation tests. Conclusion : A large proportion of patients with APS and/or SLE give false-positive HIT antigen test results that are presumably related to autoantibodies against PF4, which can be distinguished from true HIT antibodies by EIA for PF4–heparin complexes tested with heparin excess, and by functional assays.     

Current status and implications of autoimmune antiphospholipid antibodies in relation to thrombotic disease

Summary.  This review briefly describes the development of the concepts of antiphospholipid antibody and of antiphospholipid syndrome. It focuses on the two main antigenic targets, β₂ glycoprotein I and prothrombin. An excessive production of natural antibodies rather than an immune response to exogenous antigen is proposed as pathogenetic for the development of these antibodies. The review attempts to explain how some of these antibodies are anticoagulant in vitro yet prothrombotic in vivo . The final section discusses when to test for such antibodies, how to test and how to consider treatment of patients with the antiphospholipid syndrome.     

Prevalence of antiphospholipid antibodies in Chilean patients with rheumatoid arthritis

Antiphospholipid (aPL) antibodies found in patients with autoimmune diseases are also detected in those with inflammatory diseases. The purpose of this study was to examine the prevalence of these antibodies in patients with rheumatoid arthritis (RA), and to evaluate the association of these antibodies with thrombosis and/or other clinical characteristics of this inflammatory disorder. Eighty-four patients with RA and 82 normal controls were studied. Anticardiolipin (aCL), anti-beta(2) glycoprotein I (anti-beta(2)GPI), and antiprothrombin (aPT) antibodies and the lupus anticoagulant (LA) activity were determined. Seven out of 84 (8.3%) patients were positive for aCL, six out of 84 (7.2%) for anti-beta(2)GPI, and six out of 84 (7.2%) for aPT, while in controls the overall prevalence of aPL antibodies was 3.6% (3 out of 82). All patients and controls were LA negative. There was no correlation between the presence of aPL with thrombosis and/or other clinical features of the antiphospholipid syndrome. We found aPL antibodies in 19.1% (16 out of 84) of the patients with rheumatoid arthritis and this prevalence was statistically higher than in normal controls (P<0.003). In this study, the presence of aPL antibodies was not associated with the development of thrombosis and/or thrombocytopenia. Whether the presence of aPL antibodies implies an increased risk for thrombosis and atherosclerosis in these patients should be studied further.     

Alterations of cerebral blood flow and antiphospholipid antibodies in patients with systemic lupus erythematosus

Twenty-two patients with systemic lupus erythematosus and 13 healthy controls were included in a cerebral blood flow study and underwent brain-dedicated single-photon emission computed tomography using^99mtechnetium-d, 1-hexamethylpropylene amine oxime together with a brain computed tomography scan. Plasma levels of antiphospholipid antibodies (lupus anticoagulant and anticardiolipin IgM and IgG antibodies) were also determined. Brain computed tomography showed signs of focal cerebral ischemia in 4 patients (18%), whereas cerebral blood flow by single-photon emission computed tomography was abnormal in 13 of 22 patients (59%), who showed bilateral or monolateral hypoperfusion in the temporo-parietal regions. Patients with abnormal cerebral blood flow had a longer duration of disease than those with normal blood flow (8.9±1.9 years vs. 5.3±1.5 years,P<0.05). Plasma antiphospholipid antibodies were present in 15 patients (68%), but the prevalence was similar in those with normal (6/9, 66%), or abnormal (9/13, 69%) cerebral blood flow. No statistically significant difference in lupus anticoagulant or anticardiolipin antibodies was observed between patients with and without cerebral blood flow abnormalities. Our study shows that patients with systemic lupus erythematosus frequently have cerebral blood flow abnormalities, which could precede those observed by computed tomography. Plasma lupus anticoagulant and anticardiolipin titers were not correlated with normal cerebral blood flow.     

狼疮性肾炎患者心理状态分析与对策

目的 探讨狼疮性肾炎患者心理状态并提出相应的护理措施。方法 采用症状自评量表（SCL-90）进行测试。结果 患者在躯体化、强迫症状、人际敏感、抑郁、焦虑、敌意、恐怖、偏执、精神病性9个因子评分与国内常模比较，差异具有非常显著性（P〈0．01）。结论 狼疮性肾炎患者心理状态差，应加强心理护理。     

Revised classification criteria for antiphospholipid syndrome and the thrombotic risk in patients with autoimmune diseases

BACKGROUND: The classification criteria for antiphospholipid syndrome (APS) were updated in 2006. Objective: The aim of the study was to analyze associations between clinical complications and laboratory test abnormalities typical for APS in a group of patients with autoimmune diseases, based on the recently updated criteria. PATIENTS/METHODS: Three hundred and thirty-six patients were enrolled into the study, with the majority (n = 235) suffering from systemic lupus erythematosus. Laboratory determinations included: lupus anticoagulant (LA), anticardiolipin (aCL) and anti-beta(2)-glycoprotein I (anti-beta(2)GPI) antibodies (ABs) [of both immunoglobulin G (IgG) and IgM class]. RESULTS: A significant association was found between laboratory and clinical features of APS; odds ratios (ORs) for thrombosis associated with the presence of LA, aCL, and anti-beta(2)GPI Abs were 4.04 [95% CI: 2.44-6.68], 3.71 (95% CI 2.32-5.92) and 2.57 (95% CI 1.60-4.1), respectively. Detailed analysis showed marked differences between the risk of clinical complications associated with the presence of an antibody in the IgG class (OR 4.15, 95% CI 2.42-7.12, and OR 4.77, 95% CI 2.37-9.61 for aCL and anti-beta(2)GPI, respectively) and in the IgM class (OR 2.2, 95% CI 1.31-3.70, and OR 1.9, 95% CI 1.15-3.14 for aCL and anti-beta(2)GPI, respectively). The postulated inclusion of anti-beta(2)GPI antibody positivity into the previous laboratory criteria changed only slightly the number of patients diagnosed with APS (from 112 to 117). CONCLUSIONS: The updated APS classification criteria clearly represent a step forward. However, our results argue against the use of overall positivity for aCL or anti-beta(2)GPI, and favor a clear distinction between the IgG and IgM classes of antiphospholipid ABs. Patients with both LA and anti-beta(2)GPI IgG or LA and aCL IgG positivity may represent the subgroups at the highest risk of thrombotic complications.