血清抗β2糖蛋白Ⅰ抗体与系统性红斑狼疮患者心血管病变的关系

目的 探讨血清抗β2糖蛋白Ⅰ (β2-GPI)抗体与系统性红斑狼疮(SLE)患者心血管病变(CVD)的关系.方法 酶联免疫吸附试验(EHSA)检测81例SLE患者血清抗β2糖蛋白Ⅰ抗体水平,分析其与CVD相关指标、既往CVD病史的关系.采用t检验、x2检验、Spearman相关分析、Logistic多元回归分析进行统计学分析.结果 SLE患者的血清抗β2糖蛋白Ⅰ抗体水平较对照组显著升高[(29±19)和(14±8) U/ml,t=2.035,p＜0.05].81例患者中有27例(33％)既往发生CVD,而对照组仅1例(5％).SLE患者的血清抗β2糖蛋白Ⅰ抗体水平与甘油三酯(r=0.337,P＜0.05)、肾脏病变(r=0.489,P＜0.01)呈正相关;与高密度脂蛋白(r=-0.385,P＜0.05)、补体C3(r=-0.497,P＜0.05)呈负相关.既往有CVD史者血清抗β2糖蛋白Ⅰ抗体水平较既往无CVD史者显著升高[(41±25)和(18±12) U/ml,t=-2.038,P＜0.05 ].Logistic回归分析显示血清抗β2糖蛋白Ⅰ抗体(β=0.675,95％CI 0.507～0.816,p＜0.05)是SLE合并CVD的独立危险因素.结论 SLE患者CVD发生率高,抗β2糖蛋白Ⅰ抗体可能参与了SLE患者CVD的发生发展.     

抗β_2糖蛋白Ⅰ抗体在系统性红斑狼疮患者血栓形成中的作用

目的探讨抗β_2糖蛋白Ⅰ(anti-β_2-glycoprotein I,aβ_2GPI)抗体IgA、IgM、IgG在系统性红斑狼疮(systemic lupus erythematosus,SLE)血栓形成中的作用。方法收集确诊SLE患者,根据有无发生临床血栓事件分为SLE-non-APS组和SLE-APS组。选取原发性抗磷脂抗体综合征为PAPS组。这些患者均经实验室检测为aβ_2GP I抗体阳性,且排除血栓形成的传统危险因素。应用酶联免疫吸附试验检测各组患者aβ_2GPI的IgA、IgM、IgG 3类抗体水平。SLE-APS组+PAPS组患者中发生动脉血栓事件者纳入APS-A组,发生静脉血栓事件者纳入APS-V组,比较两组间上述指标。结果共纳入82例患者,SLE患者64例,原发性APS患者18例(PAPS组)。64例SLE患者中,SLE-non-APS组52例,SLE-APS组12例。SLEAPS组+PAPS组共30例,其中APS-A组23例,APS-V组7例。SLE-APS组aβ_2GPI-IgA[(1.3±0.4)×10~(-8)mol/L]、aβ_2GPI-IgM浓度[(1.0±0.2)×10~(-8)mol/L]低于SLE-non-APS组[aβ_2GPI-IgA:(1.8±0.9)×10~(-8)mol/L,aβ_2GPI-IgM:(1.5±0.7)×10~(-8)mol/L](P0.05),而两组aβ_2GPI-IgG的浓度无明显差异。SLE-APS组与PAPS组患者aβ_2GPI-IgA、aβ_2GPI-IgG、aβ_2GPI-IgM的浓度无明显差异。APS-A组aβ_2GPI-IgM浓度[(1.2±0.5)×10~(-8)mol/L]显著高于APS-V组[(0.7±0.1)×10~(-8)mol/L](P0.05),aβ_2GPI-IgG浓度显著低于APS-V组[(1.4±0.3)×10~(-8)mol/L vs.(1.7±0.3)×10~(-8)mol/L](P0.05),而两组aβ_2GPI-IgA的浓度无明显差异。结论无论有无SLE基础免疫性疾病,IgG类aβ_2GPI与静脉血栓形成有明显的关联性,IgM类aβ_2GPI与动脉血栓形成相关。     

抗心磷脂抗体与系统性红斑狼疮高血压的相关性

目的 探讨抗心磷脂抗体在系统性红斑狼疮(SLE)高血压患者中的临床意义.方法 应用酶联免疫吸附法(ELISA)检测110例SLE患者和50名健康者血清中抗心磷脂抗体IgG(IgG-ACA)、抗心磷脂抗体IgM(IgM-ACA)、抗β2糖蛋白I(β2-GP1)抗体的浓度水平.结果 SLE高血压组IgG-ACA、IgM-ACA、抗β2-GP1抗体浓度水平高于SLE正常血压组、健康对照组(P＜0.05),而SLE正常血压组与健康对照组比较差异无统计学意义(P＞0.05).结论 SLE患者合并高血压时IgG-ACA、IgM-ACA、抗β2-GP1抗体浓度水平升高,提示ACA升高与狼疮性高血压的发生有关,抗心磷脂抗体检测对预测狼疮性高血压有一定参考价值.     

β2糖蛋白Ⅰ抗β2糖蛋白Ⅰ抗体与抗磷脂综合征

抗磷脂综合征(antiphospholipid syndrome,APS)与抗磷脂抗体(antiphospholipid antibody,APL)密切相关,是以血栓形成、习惯性流产和血小板减少等症状为特点的一组综合征。APS分为原发性(primary APS,PAPS)和继发性(secondaryAPS,SAPS)两大类。近年研究表明,APL所针对的靶抗原不     

抗心磷脂抗体与系统性红斑狼疮高血压的相关性

目的探讨抗心磷脂抗体在系统性红斑狼疮(SLE)高血压患者中的临床意义。方法应用酶联免疫吸附法(ELISA)检测110例 SLE 患者和50名健康者血清中抗心磷脂抗体 IgG(IgG-ACA)、抗心磷脂抗体 IgM(IgM-ACA)、抗β_2糖蛋白Ⅰ(β_2-GP1)抗体的浓度水平。结果 SLE 高血压组 IgG-ACA、IgM-ACA、抗β_2-GP1抗体浓度水平高于 SLE 正常血压组、健康对照组(P<0.05),而 SLE 正常血压组与健康对照组比较差异无统计学意义(P>0.05)。结论 SLE 患者合并高血压时 IgG-ACA、IgM-ACA、抗β_2- GP1抗体浓度水平升高,提示 ACA 升高与狼疮性高血压的发生有关,抗心磷脂抗体检测对预测狼疮性高血压有一定参考价值。     

抗心磷脂抗体的研究进展

近年来研究表明，抗心磷脂抗体是系统性红斑狼疮的一种觉自身抗体，它与血栓形成，血小板减少及自然流产均有密切关系。     

抗β2-糖蛋白Ⅰ抗体在系统性红斑狼疮中的临床意义

目的了解抗!2-糖蛋白Ⅰ抗体(抗!2-GPⅠ抗体)与系统性红斑狼疮(SLE)临床特点的关系及在其诊断中的价值。方法采用酶联免疫吸附试验(ELISA)检测112例SLE患者、40例类风湿关节炎(RA)患者、30例干燥综合征(SS)患者和40名正常人血清中的抗!2-GPⅠ抗体水平。同时,测定患者血清中的抗心磷脂抗体(ACL)等指标,并分析其与患者的临床特点(如:血栓、流产)的关系及其临床意义。统计学分析采用t检验、!2检验和Spearman检验。结果抗!2-GPⅠ抗体在SLE中敏感性为21.4%(24/112),特异性为88.6%,在RA和SS敏感性分别为15.0%(6/40)和6.7%(2/30),40名正常对照均为阴性。抗!2-GPⅠ抗体与血栓形成密切相关(P<0.01),与ACL-IgG和IgM型水平呈正相关(r=0.479,P=-0.032;r=0.400,P=0.045)。抗!2-GPⅠ抗体与其他临床及实验室指标无明显相关性。结论抗!2-GPⅠ抗体在SLE中具有一定的敏感性,且可能在SLE的血栓形成中发挥作用,联合检测ACL与抗!2-GPⅠ抗体能够辅助诊断SLE伴血栓形成。     

抗β2糖蛋白I抗体在系统性红斑狼疮合并自身免疫性溶血性贫血中的意义

目的检测抗β2糖蛋白I抗体(β2 glycoprotein I,aβ2GPI)等多种自身抗体在系统性红斑狼疮(systemic lupus erythematous,SLE)并发自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)患者的阳性率,评估aβ2GPI在并发AIHA的SLE患者中的意义。方法收集2008年12月至2013年4月福建医科大学附属第一医院风湿科门诊和病房SLE患者资料,根据有无发生AIHA分为SLE-AIHA组和SLE-non-AIHA组。选取AIHA患者为AIHA组。检测IgM和IgG类的aβ2GPI、抗心磷脂抗体(anticardiolipin,ACL),以及抗Sm抗体、核小体抗体、组蛋白抗体、核糖体P蛋白抗体等多种自身抗体,采用SPSS11.5软件统计分析。结果共纳入SLE患者104例,SLE-AIHA组22例,SLE-non-AIHA组82例;AIHA组20例。SLE-AIHA组和SLE-non-AIHA组在年龄、性别、病程、受累器官等方面均无统计学差异;而SLE-AIHA组的IgG类aβ2GPI阳性率达45.5%,显著高于SLE-non-AIHA组的15.9%,差异有统计学意义(P0.01);两组患者的IgM类aβ2GPI、IgM和IgG类ACL、抗Sm抗体、核小体抗体、组蛋白抗体、核糖体P蛋白抗体阳性率比较差异均无统计学意义(均P0.05);SLE-AIHA组和AIHA组患者aβ2GPI和ACL阳性率比较差异均无统计学意义(均P0.05);SLE-AIHA组IgG类aβ2GPI阳性患者肾损害发生率高于该抗体阴性者,差异有统计学意义(P0.05)。结论 IgG类aβ2GPI在并发AIHA SLE患者和原发性AIHA患者中均表现较高阳性率,可能是SLE并发AIHA的重要血清学特征;同时该抗体可能是继溶血事件后加重狼疮患者肾损害的重要因素之一。     

Serum anti-beta2-glycoprotein-I and anticardiolipin antibodies during thrombosis in systemic lupus erythematosus patients

PURPOSE: Antibodies to beta2-glycoprotein-I are more strongly associated with clinical antiphospholipid syndrome than are anticardiolipin antibodies. We previously found a decrease in anticardiolipin antibodies at the time of thrombosis in 6 patients with systemic lupus erythematosus (SLE). We therefore sought to determine the prevalence and levels of antibodies to beta2-glycoprotein-I and to cardiolipin before, during, and after thrombosis in patients with SLE, and to compare them with patients who did not have thrombosis. METHODS: We studied 24 patients with SLE who had at least one episode of thrombosis and 102 patients with SLE without thrombosis. Serum anticardiolipin antibodies were measured by conventional enzyme-linked immunosorbent assay (ELISA) using newborn calf serum as the blocking agent. Serum anti-beta2-glycoprotein-I antibodies were measured by ELISA on nonirradiated plates, using purified human beta2-glycoprotein-I without phospholipid. RESULTS: All patients with thrombosis had anti-beta2-glycoprotein-I antibodies, compared with only 17% of controls (P <0.0001). We observed a significant decrease in serum anti-beta2-glycoprotein-I levels at the time of thrombosis, as compared with previous and subsequent samples. The prevalence and levels of IgG and IgM anticardiolipin antibodies were similar in patients with and without thrombosis. A decrease in IgG or IgM anticardiolipin titers occurred during thrombosis in 6 patients. Anticoagulant, corticosteroid, and immunosuppressive treatments did not appear to affect anti-beta2-glycoprotein-I levels at the time of thrombosis. CONCLUSION: Anti-beta2-glycoprotein-I antibodies are strongly associated with thrombosis in patients with SLE. The decrease of anti-beta2-glycoprotein-I levels at the time of thrombosis may indicate a pathogenic role. This antibody may also be a marker of predisposition for thrombosis in these patients.     

Specificity and sensitivity of anti-beta2-glycoprotein I as compared with anticardiolipin antibody and lupus anticoagulant in Thai systemic lupus erythematosus patients with clinical features of antiphospholipid syndrome

Antibodies to beta(2)-glycoprotein I (anti-beta(2)-GPI) have been reported to have stronger association with clinical antiphospholipid syndrome (APS) than anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). We investigated the sensitivity and specificity of ELISA for anti-beta(2)-GPI in Thai systemic lupus erythematosus (SLE) patients with clinical features of APS and compared the results with IgG/IgM aCL and LAC to find the test with the best association. The hospital records of 151 Thai SLE patients whose sera had been sent for either IgG/IgM anticardiolipin antibodies or lupus anticoagulant testing were reviewed. Sera of patients either without complete clinical records or those with APS-related manifestations other than vascular thrombosis and pregnancy morbidity (according to the international consensus statement on preliminary classification criteria for definite APS) were excluded. For the remaining subjects (112 patients), their sera were tested for anti-beta(2)-GPI antibody, IgG and IgM anticardiolipin, and lupus anticoagulant. The sensitivity and specificity of each method were compared by using the chi-square test. Among the 112 (74.2%) SLE patients in the study, 35 (31.3%) presented with preliminary clinical criteria for APS (i.e., vascular thrombosis and pregnancy morbidity) whereas 77 (68.7%) did not. The sensitivity and specificity of anti-beta(2)-GPI determination were 57.1 and 79.2%, respectively, whereas those of IgG aCL were 25.7 and 94.8%, of IgM aCL were 5.7 and 98.7%, and of LAC were 44.8 and 77.3%, respectively. The accuracy of the four tests showed similar association with clinical APS (accuracy of test = 72.3, 73.2, 69.6, and 68.3%, respectively). Concerning the sensitivity, specificity, and difficulty of the methods, the combination of anti-beta(2)-GPI and IgG aCL tests was the best for the diagnosis of APS in Thai SLE patients.     

Distribution and clinical significance of lupus anticoagulant and anticardiolipin antibody in 349 patients with systemic lupus erythematosus.

Samples from 349 patients with systemic lupus erythematosus (SLE) were tested simultaneously for lupus anticoagulant (LAC) and anticardiolipin antibodies (ACL). LAC was detected in 27.2% of 349 SLE patients by a modified mixing kaolin clotting time. ACL was detected in 34.7% by enzyme-linked immunosorbent assay. Only half of the patients who had LAC or ACL were positive for both of them. In addition, isotypes of ACL in these patients were studied. The IgG isotype was detected in 81.8% of 121 patients, and more than half had only the IgG isotype. When clinical features of patients with LAC or ACL were studied, the incidence of thrombosis, fetal loss, and thrombocytopenia were significantly higher in both groups compared with patients without LAC or ACL. In particular, the patients with both LAC and ACL showed the highest risk of fetal loss (89%) during pregnancy. These results indicate that LAC and ACL are detected in partly different groups of SLE patients, but both of these groups are clinically similar.     

IgA anticardiolipin and anti-beta2-glycoprotein I are the most prevalent isotypes in African American patients with systemic lupus erythematosus.

BACKGROUND: Ethnicity plays a role in the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2-glycoprotein I (anti-beta2-GPI) antibodies in patients with systemic lupus erythematosus (SLE). Few studies have been done in the African American population. METHODS: Serum samples from 100 African American patients with SLE were tested for IgG, IgM, and IgA aCL and anti-beta2-GPI antibodies by enzyme-linked immunosorbent assay (ELISA). Computerized clinical data on these patients were reviewed with a specific focus on clinical manifestations of antiphospholipid syndrome (APS). RESULTS: Positivity for at least one isotype of aCL antibodies was found in 33% of the patients, whereas 28% were positive for at least one isotype of anti-beta2-GPI antibodies. IgA was the most prevalent isotype for both antibodies; 24% of the patients in the aCL ELISA and 19% in the anti-beta2-GPI ELISA were positive for IgA. Positivity for both aCL and anti-beta2-GPI in the same patient was seen more frequently with the IgA isotype. Fewer than half of the patients positive for aCL antibodies had medium-to-high levels of antibodies. A few patients had presented thrombotic manifestations, and these patients were positive for aCL (P = 0.01) and anti-beta2-GPI antibodies (P = 0.02). No other manifestations of APS could be significantly correlated with the presence of these antibodies. CONCLUSIONS: Our results show that IgA is the most prevalent isotype among the African American patients with SLE studied. The predominance of the IgA isotype and the low prevalence of medium-to-high levels of aCL antibodies may account for the low frequency of clinical manifestations of APS in these patients.     

Anti-annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody

We investigated anti-annexin V antibody (aANX) in patients with systemic lupus erythe-matosus (SLE), and correlated to positivity with lupus anticoagulant (LA)/anticardiolipin antibody (aCL). aANX was positive in 12/47 SLE patients (26%), including 7 with β₂-glycoprotein 1 (GPl)-dependent aANX. The positivity of aANX was higher in patients with aCL (19%) and LA/aCL (50%) than in those without LA/aCL (10%). From these results, it is concluded that aANX is an autoantibody closely related to LA/aCL, and can be a possible new risk marker for thrombosis. © 1994 Wiley-Liss, Inc.     

IgG subclass distribution of anticardiolipin antibody in patients with systemic lupus erythematosus

IgG subclass distributions of anticardiolipin (aCL), anti-ssDNA, and anti-dsDNA antibodies in sera of patients with systemic lupus erythematosus were determined by an enzyme linked immunoassay (ELISA) method, using mouse monoclonal antihuman IgG subclass antibodies. IgG aCL activity consisted mainly of the IgG1 subclass, and to some extent, the IgG3 subclass. Definite amounts of aCL activity were also detected in IgG2 in sera from 25% of the patients. Anti-ssDNA antibody activity was relatively equally distributed among IgG1, IgG2 and IgG3, but was poorly distributed in IgG4. In contrast, anti-dsDNA antibody activity consisted mainly of IgG1 and IgG3.     

Anti-cardiolipin and anti-beta2 glycoprotein I antibodies in Indian patients with systemic lupus erythematosus: association with the presence of seizures

The aim of this study was to examine whether the clinical features of antiphospholipid antibody syndrome are associated with anti-cardiolipin and anti-beta2 glycoprotein I antibodies in Indian patients with SLE. Seventy-six patients (71 females), who fulfilled 1982 ACR criteria for SLE, were prospectively studied for the clinical features of antiphospholipid antibody syndrome (APS), and their sera were analysed for the presence of IgG/IgM/IgA anti-cardiolipin antibodies (aCL) by an in-house ELISA and, in 65 of them, for the presence of IgG anti-beta2 glycoprotein I antibodies (anti-beta2 GPI) by a commercial kit. Thirty-nine (51%) patients were positive for aCL, all of which were positive for IgG aCL, either alone (79.6%) or along with IgM and/or IgA. Twenty-seven (69.3%) out of 39 aCL-positive and seven (26.9%) out of 26 aCL-negative sera were positive for IgG antibodies to beta2 GPI. There was a significant correlation (r = 0.66, P < 0.05) between the levels of aCL and anti-beta2 GPI antibodies. Forty-one patients had features of definite or suggestive APS. Thrombocytopenia, recurrent pregnancy loss and CNS manifestations (seizures eight, infarct one) were seen in 20, 13 and nine patients, respectively. Thrombosis of the peripheral vessels was seen in only one patient. Only the presence of seizures was significantly associated with the presence of aCL and anti-beta2 GPI antibodies (P < 0.05). The characteristic association of definite APS (recurrent pregnancy loss and arterial/venous thrombosis) was lacking.     

Association of anti-beta 2 glycoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus.

PURPOSE: Antiphospholipid antibodies (including anticardiolipin antibodies and circulating anticoagulant) are associated with thrombosis in systemic lupus erythematosus. Since it has been shown that beta 2 glycoprotein I (beta 2 gp I) acts as a cofactor of anticardiolipin antibody binding to cardiolipin, the presence and clinical meaning of anti-beta 2gp I antibodies in sera from patients with lupus were examined. PATIENTS AND METHODS: An enzyme-linked immunosorbent assay technique for the detection of anti-beta 2gp I antibodies was developed, and 47 lupus sera were studied retrospectively, as well as 88 healthy blood donors' sera. RESULTS: It was found that 17 of 47 patients with lupus (36%) had anti-beta 2gp I antibodies. Anti-beta 2gp I antibodies were statistically associated with anticardiolipin antibodies, thrombosis, and lupus anticoagulant. Eight of nine lupus patients with thrombosis had anti-beta 2gp I antibodies and lupus anticoagulant, and seven of them had anticardiolipin antibodies. Of 18 patients with anticardiolipin antibodies without anti-beta 2gp I antibodies or lupus anticoagulant, only one had thrombosis (due to nephrotic syndrome). Among anti-beta 2gp I-positive patients, 14 of 16 had lupus anticoagulant activity, whereas only three patients with lupus anticoagulant were anti-beta 2gp I-negative. CONCLUSIONS: The presence of anti-beta 2gp I antibodies is a new immunologic feature of lupus patients with thrombosis. In addition, since anti-beta 2gp I antibodies are closely associated with lupus anticoagulant activity, they may contribute to explain antiprothrombinase activity.