抗磷脂抗体综合征的发病机制和临床实验诊断方法的现在与未来

抗磷脂抗体综合征(antiphospholipid syndrome，APS)在临床上表现为反复的动脉、静脉血栓、习惯性流产和血小板减少等，这些症状可单一出现或多个共同存在。在患者的血清中可检出狼疮抗凝因子(lupus anticoagulant，LA)或抗心磷脂抗体(anticar diolipin antibody，aCL)。APS的基本病理改变表现     

复发性流产患者联合检测三种血清自身抗体及临床意义

目的:探讨血清抗心磷脂抗体(anticardiolipin antibody,ACL)、抗β2-糖蛋白Ⅰ抗体(anti-beta2-glycoproteinI antibody,抗β2-GPI抗体)和狼疮抗凝物(lupus anticoagulant antibody,LAC)联合检测对复发性流产(reeurrent spontaneous abortion,RSA)的预测意义.方法:选取85例RSA患者为实验组,50例正常经产妇作为对照组,检测两组血清ACL、抗β2-GP1抗体和LAC水平.结果:RSA组ACL阳性率为27.06％(23/85),而对照组为8％(4/50),差异有统计学意义(P＜0.01);抗β2-GPI抗体阳性率为21.18％(18/85),而对照组2％(1/50),差异有统计学意义(P＜ 0.01);LAC阳性率为21.18％(18/85),而对照组为6％(3/50),差异有统计学意义(P＜0.05).在确诊的40例抗磷脂抗体综合症患者中,ACL或抗β2-GPI抗体阳性率为95.00％(38/40),和ACL或LAC阳性组比较,差异有统计学意义(P＜0.01);和抗β2-GPI抗体或LAC阳性组比较,差异有统计学意义(P＜0.05).结论:(1) ACL、抗β2-GPI抗体和LAC均与RSA有关.(2)ACL和抗β2-GPI抗体联合检测可以提高RSA患者抗磷脂抗体综合症检出率,对于临床诊断和指导治疗有重要意义.     

抗磷脂抗体综合征的实验与临床

抗磷脂抗体（antiphospholipid antibody,APA）的本质仍不清楚,但大多学认为是一组酸性磷脂的异质性自身抗体的总称.它包括狼疮抗凝因子（lupus anticoagulant,LA）、抗心磷脂抗体（anticardiolipin antibodies,ACA）两大类,抗磷脂酸抗体、抗磷脂酰丝氨酸抗体、抗磷脂酰乙醇胺抗体、抗磷脂酰胆碱抗体、抗磷脂酰肌醇抗体等均可归于这两大类中.     

抗磷脂综合征

近年来,一些学者发现系统性红斑狼疮(SLE)及某些自身免疫性疾病患者血清中存在抗磷脂抗体(APLA),包括狼疮抗凝物质(LA)和抗心磷脂(ACL).随着研究的深入,对APLA的临床意义获得了较多的认识,发现静脉和动脉血栓、神经精神症状、血小板减少,反复流产等临床表现与APLA密切相关,并提出血清中具有APLA的患者伴静脉和/或动脉血栓、血小板减少等表现者称抗磷脂综合征(APS).本文复习有关文献,对APS作一综述.一、APLA的生物学特性和发生率     

抗磷脂综合征致矢状窦血栓1例护理体会

抗磷脂综合征 (APS)是指由抗磷脂抗体 (APL抗体 )引起的一组临床征象的总称。APL抗体是一组能与多种含有磷脂结构的抗原物质发生反应的抗体 ,包括狼疮抗凝物 (LA)、抗心磷脂抗体 (ACL抗体 )、抗磷脂酸抗体和抗磷脂酰丝氨酸抗体等。与APL抗体有关的临床表现主要为血栓形成、习惯     

系统性红斑狼疮继发抗磷脂抗体综合征临床分析

目的:探讨系统性红斑狼疮(system ic lupus erythematosus,SLE)继发抗磷脂抗体综合征(antiphospholipid syndrome,APS)的临床特点、实验室指标及相关因素,以早期发现继发性APS。方法:回顾性分析2005年1月至2014年1月收集的129例SLE和APS患者的临床资料,包括临床表现、妊娠情况、抗核抗体、抗心磷脂抗体等。结果:129例患者中,原发性APS(primary antiphospholipid syndrome,PAPS)8例;SLE者121例,其中SLE合并APS患者(SLE-APS)41例,仅诊断为SLE患者(SLE-APA-)40例及出现抗磷脂抗体(antiphospholipid antibody,APA)异常但APS诊断依据不足(SLE-APA+)的SLE患者40例。8例原发性APS患者中,3例男性均表现为下肢深静脉血栓形成及手微动脉血栓形成,有婚育史的女性患者中5例均有病态妊娠表现,自发性流产和(或)死胎,其中2例有肺栓塞、门(脾)静脉栓塞。41例SLE-APS患者中,表现为下肢深静脉血栓有15例,肺栓塞患者3例,脑梗死10例;SLE-APS组抗β2-糖蛋白1(抗β2-GP-1)浓度明显高于SLE-APA+组及SLE-APA-组,而血小板计数明显减低。结论:SLE合并APS患者的血清中存在高浓度抗β2-GP-1,提示高浓度抗β2-GP-1是SLE继发APS的独立危险因素。     

435例不孕女性免疫性抗体检测结果分析

目的 探讨抗精子抗体(antisperm antibody,AsAb)、抗子宫内膜抗体(antiendometrial antibody,EmAb)和抗心磷脂抗体(anticardiolipin antibody,AcAb)在女性不孕中的作用.方法 采用ELISA方法检测435例女性不孕患者血清AsAb,EmAb和AcAb.结果 AsAb阳性48例(11.03％),EmAb阳性61例(14.02％),AcAb阳性40例(9.20％);AsAb+EmAb阳性21例(4.83％),AsAb+AcAb阳性11例(2.53％),EmAb+ AcAb阳性9例(2.07％),未发现3种抗体同时阳性患者.结论 AsAb,EmAb和AcAb是引起女性不孕的重要免疫学因素,应作为不孕女性常规检查项目.     

抗磷脂综合征发病机制及诊治进展

抗磷脂综合征(antiphospholipid syndrome,APS)主要表现为血栓形成或病态妊娠,实验室检测抗磷脂抗体(an-tiphospholipid antibody,APL)阳性,如抗心磷脂抗体(anticardiolipin antibody,ACA)、抗β2-糖蛋白1(β2-glycoprotein l,β2-GP1)抗体及狼疮抗凝物(lupus anticoagulant,LAC)。β2-GP1及其抗体在APS发病机理中的作用日益受到人们的重视。APS累及全身多个系统,治疗上除肝素、华法林和阿司匹林外,还可试用免疫抑制剂、大剂量丙种球蛋白等,其他与发病机制相关的免疫治疗仍在进一步研究中。     

系统性红斑狼疮患者血栓形成与抗β2-糖蛋白Ⅰ抗体、狼疮抗凝物的联合检测临床意义

系统性红斑狼疮（systemic lupus erythematosus，SLE）是一种自身免疫性疾病，可以引起全身多脏器损害，临床上常出现静脉血栓、血小板减少、溶血性贫血、皮肤网状青斑及神经系统改变等表现，许多研究表明SLE的许多临床表现与血栓形成密切相关。狼疮抗凝物（lupus anticoagulant，LA）是一种磷脂依赖性的病理性循环抗凝物质，为IgG、IgM或两者混合型的抗磷脂抗体。     

不同亚型ACL和aβ2GPⅠ在SLE患者发病及病情发展中的临床意义

目的 探讨不同亚型抗心磷脂抗体(ACL)与抗β2糖蛋白Ⅰ抗体(aβ2GPⅠ)在系统性红斑狼疮(SLE)患者发病及病情发展中的临床意义.方法 将该院2017年2月至2019年2月收治的73例SLE患者纳为SLE组,30例非SLE结缔组织病患者纳为对照组A,30例健康体检者纳为对照组B,应用IgA/G/M多亚型筛选试剂与I...     

Autoimmune hemolytic anemia as an initial presentation in children with systemic lupus erythematosus: two case reports

We report the cases of two children who presented with autoimmune hemolytic anemia (AIHA) as an initial presentation of systemic lupus erythematosus (SLE). Both patients had a positive Coombs test, anemia, and an increased number of spherocytes in their blood smear. The patient in Case 1 presented with fever, urticarial erythema, facial paresis, AIHA, and leucopenia. Immunological screening revealed low complement protein levels and positive anti-nuclear antibody, anti-double-stranded DNA, and antiphospholipid antibody results. A further laboratory workup revealed a positive lupus anticoagulant (LA) result and low factor II levels. She was diagnosed with lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) in addition to SLE. The patient in Case 2 presented with fever, butterfly rash, thyroid enlargement, leucopenia, and AIHA. She was diagnosed with SLE with thyroiditis. Both patients were started on combined immunosuppressive therapy, and both patients’ clinical symptoms finally resolved. A literature review on childhood SLE showed that AIHA is common in patients with SLE. LAHPS is an uncommonly identified cause of bleeding in patients with SLE, and it must be considered when evaluating children with a positive LA result.     

Lupus nephritis as a factor of atherosclerosis risk in patients with systemic lupus erythematosus

AIM: To investigate early atherosclerosis (AS) risk factors in patients with systemic lupus erythematosus (SLE) in respect to the presence of lupus nephritis (LN) and antiphospholipid (APL) antibodies. MATERIAL AND METHODS: We analysed case histories of 137 SLE patients observed in E.M. Tareev clinic from 1970 to 2006. AS manifestations were studied by echocardiography, ultrasonic dopplerography of the peripheral vessels, x-ray methods. AS was considered early if it arose at the age under 55 years. Patients with chronic renal failure were not included in the study. RESULTS: AS development was seen in 54 (45%) patients, early symptoms appeared at the age of 25-68 years (mean 54 +/- 10 years). In 37 (31%) patients AS symptoms manifested at the age under 55 years. Significant factors of early AS risk were age, hyperlipidemia, arterial hypertension, menopause for women, APL antibodies circulation, stage IV chronic disease of the kidneys, hyperuricemia, higher blood creatinine, mean dose of prednisolone over 15 mg/day, frequent elevation of the level of C-reactive protein. A direct correlation between lupus nephritis or nephrotic syndrome (NS) and early AS was not found. In LN hyperlipidemia occurred more often (p = 0.055), lipids level and NS were not related during its remission. LN patients developed AS more frequently, had lower complement concentration in the end of the study, were treated with prednisolone more intensively than patients free of renal disease (p < 0.05). CONCLUSION: Early AS develops in more than one third of SLE patients. Main risk factors of early AS are conventional ones and APL antibodies, persistence of chronic inflammation, decreased glomerular filtration rate, prednisolone therapy. LN influence on the process of atherogenesis in SLE may be mediated and caused by high rate of other risk factors.     

系统性红斑狼疮合并抗磷脂综合征患者的临床分析

目的 研究系统性红斑狼疮合并抗磷脂综合征(SLE-APS)患者的临床特点.方法 对39例SLE-APS患者的临床和实验室资料进行回顾性分析.结果 39例患者中,有31例共发生了48次血栓栓塞事件,以深静脉血栓及脑梗死为主.26例已婚有生育史女性患者中,有12例发生病态妊娠.28例抗心磷脂抗体阳性;16例狼疮抗凝物阳性.24例患者先确诊SLE,平均9.5年后又出现APS样表现;12例先出现反复病态妊娠或血栓事件,平均4.8年后演变为SLE;3例一发病便同时符合SLE和APS的分类标准.有5例在发生血栓事件或病态妊娠时的狼疮活动指数<5分.结论 SLE-APS患者血栓事件及病态妊娠发生率增多.APS可出现于SLE之前、之后或同时.狼疮患者可以在病情稳定期出现APS的表现.详细询问病史、常规检测抗心磷脂抗体,有助于发现SLE-APS的高危因素,积极预防APS的发生.     

Catastrophic antiphospholipid syndrome: diagnosis and treatment

AIM: To analyse data on patients who developed catastrophic antiphospholipid syndrome (CAPS) in primary and secondary APS, to assess outcomes of CAPS. MATERIAL AND METHODS: We analysed retrospectively the data on 164 patients with systemic lupus erythematosus (SLE) and APS, on 76 patients with primary APS (PAPS) treated in the Institute of Rheumatology from 1989. Verification of vascular complications was made using ultrasonic dopplerography (UDG) of peripheral vessels, echocardiography of the heart, CT of the brain, abdominal organs. Anticardiolipin antibodies (ACLab) and lupus anticoagulant (LA) served as serological markers of APS. RESULTS: In the observation period of 9.4 +/- 4.2 years, 33 patients (23 females and 10 males) out of 164 patients with SLE+APS developed CAPS, 8 of them survived while 25 died. CAPS patients had no differences by age, duration of the disease, its activity and symptoms from patients who had no CAPS. Ten out of 76 patients with PAPS developed CAPS, 7 of them died. The analysis of the concomitant factors which may initiate PAPS showed that in SLE and APS these factors consisted of initial menopause (n = 2), infection (n = 12), including pneumonia (n = 7), acute respiratory disease (n = 3), food poisoning (n = 1), abscess (n = 1). Cancer was in one patient, trauma after road accident in one patient. Trigger factor was not determined in 13 patients. In PAPS provoking factors were pneumonia (n = 2) and abscess (n = 1), in 7 patients these factors were not detected. CONCLUSION: Any infection in SLE patients should be adequately treated with antibiotics; APS patients treated surgically should receive parenteral anticoagulants instead of oral ones; puerperas with APS must receive adequate parenteral anticoagulant therapy for at least 6 weeks; in exacerbation of SLE, APS patients should receive parenteral anticoagulants with following hypocoagulation with oral anticoagulants.     

系统性红斑狼疮抗活化的蛋白C研究

目的了解抗活化的蛋白C(APCR)在系统性红斑(SLE)患者中的发生情况,并进一步探讨SLE患者发生血栓的机制。方法采用APG-KPTT法,ELISA法和PTT-LA法分别对36例SLE患者及20例正常对照(NC)进行APCR、抗心磷脂抗体(ACA)和狼疮抗凝物(LA)检测。结果SLE患者APCR阳性率(58%)明显高于NC组(5%)(P<0.005),APCR阳性患者中血栓发生率(27.6%)明显高于APCR阴性患者(4.8%)(P<0.01),患者LA阳性率(22%)明显高于对照组(0/10)(P<0.05),患者ACA-IgG及IgM明显高于对照组(P<0.05),而IgA与对照组差异不显著(P>0.05),LA阳性组中的APCR阳性率(90.9%)明显高于LA阴性组(53.8%)(P<0.05),ACA阳性组中的APCR阳性率(64.7%)与ACA阴性组(60.6%)未发现明显相关性(P>0.05)。结论APCR在国人SLE患者中有较高的发生率且与LA有明显相关性。APCR可能是SLE患者诱发血栓的主要原因之一。     

Mutation of a 5,10-methylenetetrahydrofolate reductase gene in systemic lupus erythematosis and antiphospholipid syndrome

AIM: To study prevalence of mutation C677T in gene 5.10-MTHFR in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) as well as in persons free of symptoms of systemic diseases of the connective tissue. MATERIAL AND METHODS: 85 patients participating in the study were divided into three groups: those with SLE (n = 17), with SLE + APS (n = 42), with primary APS (n = 26). The control group consisted of 30 persons without SLE or APS. 55% of the examinees had thrombotic complications of different location. The diagnosis of the mutation was made using DNA isolated from the peripheral blood with standard methods and polymerase chain reaction. Allele (homozygous or heterozygous) condition of the mutation was confirmed by means of allele-specific primers. RESULTS: Mutation C677T in MTHFR gene was found in 40 of 85 patients (47%); 11(27.5%) had a homozygous variant, 29(72.5%)--heterozygous. C677T mutation occurred in 5 of 17 SLE patients (29%), it was in all the cases heterozygous. In primary and secondary APS mutation was detected in 51.5% (35 of 68 patients). Recurrent thrombosis occurred more frequently in patients with mutation MTHFR. Three and more episodes of thrombosis were registered in 17 of 40 patients with mutation C677T against 9 of 44 patients without the mutations (p = 0.04). CONCLUSION: Relationship between elevated blood levels of APL and MTHFR mutation points to the fact that this genetic marker is an additional thrombogenic factor in APS. Mutation C677T in MTHFR gene in APS patients correlates with recurrent thrombosis.     

系统性红斑狼疮患者中检测ANCA临床意义的研究

目的探讨抗中性粒细胞胞浆抗体（ANcA）在系统性红斑狼疮（SLE）患者中检测的临床意义。方法通过间接免疫荧光法和免疫印迹法分别检测了25例健康对照组和106例SLE患者血清中的ANCA、抗核抗体（ANA）、抗双链DNA抗体、抗-SmDI抗体。结果对照组测定均为阴性。SLE患者中ANCA阳性率为47．2％（50／106）,且均为环细胞核着色的核周型（pANCA）;在ANCA阳性组及ANCA阴性组中：ANA及抗-SmDl抗体阳性率分别为100％（50／50）、91．1％（51／56）：829／0（41／50）、67．9％（38／56）,P均〉0．05;抗ds—DNA抗体阳性率分别为94％（47／50）、50％（Z8／56）,P〈0．01。在活动性sLE（52例）和非活动性sLE（54例）中ANCA阳性率分别为84．6％（44／52）;11．1％（6／54）,P〈O．01。结论ANCA在sLE患者中检测与ANA及抗-SmD1抗体没有相关性,与抗ds—DNA抗体正相关,活动期SLE患者中ANCA阳性率明显高于非活动期的患者。     

ELISA法联合CLIFT法检测抗双链DNA-IgG抗体应用于系统性红斑狼疮的诊断价值

目的：采用酶联免疫吸附试验（enzyme-linked immunosorbent assay, ELISA）, 观察抗双链DNA（double-stranded DNA, dsDNA）IgG抗体在系统性红斑狼疮（systemic lupus erythematosus, SLE）患者和非SLE患者中的分布特点, 并评估ELISA法联合绿蝇短膜虫间接免疫荧光试验（crithidia luciliae immunofluorescence test, CLIFT）检测抗dsDNA-IgG抗体用于SLE诊断的效能。方法：收集上海交通大学医学院附属瑞金医院检测抗dsDNA-IgG抗体的住院患者的临床资料, 共4 726例采用ELISA法, 其中830例同时采用CLIFT检测, 用受试者工作特征曲线（receiver operating characteristic curve, ROC）分析2种检测方法辅助诊断SLE的效能。结果：采用ELISA法检测的 4 726例住院患者中, dsDNA抗体阳性者398例, 其中SLE 183例, 占dsDNA 阳性者46.0%, 非 SLE疾病依次为肝脏疾病（28.4%）、其他结缔组织病（7.5%）、血液系统疾病（5.3%）及呼吸系统疾病（3.8%）;830例采用CLIFT检测ds DNA, 134例结果显示为dsDNA抗体阳性的患者中, 其中SLE者占94.0%, 另有非SLE诊断病例包括自身免疫性肝病3例, 肝硬化、肾炎、银屑病和抗磷脂综合征各1例。830例完成ELISA法与CLIFT双检测的患者中, SLE患者共197例, 非SLE患者633例, ELISA法检测灵敏度为74.6%, 特异度仅为92.9%;而CLIFT法测dsDNA抗体具有较高的特异度, 为98.7%, 灵敏度为64.0%。联合2种方法平行检测dsDNA抗体可明显提高SLE的诊断效能, ROC曲线下面积最高（0.869 0）。结论：单独应用ELISA法时, 应警惕假阳性较高, 需排除其他非SLE疾病的诊断;联合使用ELISA法和CLIFT法检测抗dsDNA抗体可较单独应用CLIFT法明显提高SLE的诊断效能, 二者联合平行检测结果为阴性, 用于排除SLE更有意义。     

Uterine-umbilical artery Doppler velocimetry in pregnant women with systemic lupus erythematosus.

We evaluated continuous wave uterine-umbilical artery Doppler velocimetry for predicting pregnancy outcome in women with systemic lupus erythematosus (SLE). Lupus anticoagulant (LAC) and anticardiolipin (ACL) antibody status also were correlated with Doppler results and outcome. Three Doppler vascular patterns were identified in 27 pregnancies of 26 women with SLE. Patients with normal flow velocity in both vessels had normal outcomes (n = 18). Reduced flow velocity of the umbilical artery only was present in five women, whose newborn infants were of lesser gestational age and birthweight, two being small for gestational age. In four pregnancies reduced flow velocity was noted in both vessels. These cases had the poorest outcome, with three perinatal losses and all fetuses being small for gestational age. Doppler velocimetry showed 100% sensitivity and negative predictive value in the detection of the small for gestational age fetus and abnormal antepartum fetal heart rate tracing. Fourteen of 18 women with normal Doppler studies did not have preeclampsia or SLE flare-ups, whereas all nine women with abnormal Doppler studies had such complications. In all 27 pregnancies the women were screened for LAC, and 21 women also were tested for the ACL antibody. Poor correlation was found between antiphospholipid antibody status and Doppler results in three of the six pregnancies with positive antibody testing the patients had normal Doppler studies and outcomes. Thus, Doppler velocimetry may help determine when these substances will affect the outcome adversely. In this study the umbilical-placental vascular system was affected more often. Uterine-umbilical arterial Doppler velocimetry uniquely identified the fetus at risk for adverse perinatal outcome in pregnancies complicated by SLE. Thus, it is a potentially valuable tool in clarifying the pathophysiology and in the management of SLE in pregnancy.