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。     

抗膜联蛋白A2抗体在抗磷脂综合征中的作用

目的 研究抗膜联蛋白A2抗体在抗磷脂综合征(APS)、系统性红斑狼疮(SLE)的血栓/病态妊娠中的可能作用.方法 先用分子克隆方法表达纯化出重组膜联蛋白A2,然后以重组膜联蛋白A2为抗原,采用酶联免疫吸附试验(ELISA)法分别检测了,101例APS患者,41例SLE合并血栓患者,124例无血栓的SLE患者及120名健康人的血清中IgG型抗膜联蛋白A2抗体水平.结果 APS组和SLE合并血栓组的IgC型抗膜联蛋白A2抗体阳性率分别为21.8%,26.8%,均品著高于单纯SLE组(6.5%)(P值均<0.0.).IgG型抗膜联蛋白A2抗体与血栓/病态妊娠有关联(P<0.01).IgG型抗膜联蛋白A2抗体对血栓/病态妊娠诊断的敏感性、特异性、预测值分别为0.232、0.935、0.805.结论 IgG型抗膜联蛋白A2抗体与APS和SLE患者的血栓/病态妊娠表现相关,将有助于一些潜在的APS患者的诊断.     

抗血小板生成素抗体与系统性红斑狼疮伴血小板减少的相关性研究

目的 分析抗血小板生成素(TPO)抗体在系统性红斑狼疮(SLE)中的作用,并探讨其与SLE伴血小板减少及病情的相关性.方法 应用酶联免疫吸附试验(ELISA)检测56例SLE患者中的抗TPO抗体,并与20例免疫性血小板减少性紫癜(ITP)及20名健康人对照.同时分析SLE患者临床特点.正态分布的计数资料采用x2检验或Fisher精确检验,计量资料采用t检验,非正态分布采用M(Q)表示及Wilcoxon's rank检验.结果 抗TPO抗体在SLE组中阳性率为39％,35％的免疫性血小板减少患者抗TPO抗体阳性,而健康对照中未能检测到抗TPO抗体(x2=11.058,P=0.001).26例伴发血小板减少的SLE患者中,15例(58％)抗TPO抗体阳性,而30例无血小板减少患者中仅有7例(23％,x2=6.894,P=0.009);进一步分析发现抗TPO体抗体阳性患者其血小板下降程度重(t=3.010,P=0.004).对照抗TPO抗体阳性与阴性患者的临床资料显示,关节炎(x2=5.959,P=0.015)、抗双链DNA(dsDNA)抗体阳性(x2=5.959,P=0.015)的SLE患者更易产生抗TPO抗体.结论 在伴发血小板减少的SLE患者中检测出较高阳性率的抗TPO抗体表明该抗体可能在SLE发生血小板减少的过程中起重要作用.在伴发血小板减少的SLE患者中检测该抗体具有一定的临床价值.     

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.     

抗核小体抗体、抗双链DNA抗体和抗超敏双链DNA抗体与系统性红斑狼疮的相关性研究

目的 通过检测系统性红斑狼疮(SLE)患者血清中抗核小体抗体(AnuA)、抗双链DNA (dsDNA)抗体和抗超敏双链DNA (dsDNA-NcX)抗体的水平,分析其在SLE患者中的敏感性、特异性及与其他实验室指标的相关性.方法 采用酶联免疫吸附试验(ELISA)法分别检测91例SLE患者、45例非SLE疾病对照和46例健康对照组血清中AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体的水平,比较3种抗体对SLE诊断的敏感性和特异性,评价其与其他实验室指标的关系.结果 SLE患者AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体的阳性率分别为49.45％、56.04％和61.54％;特异性分别为94.51％、94.51％和100.00％.AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体均与SLEDAI评分呈正相关(r=0.50,P=0.00;r =0.49,P=0.00;r =0.42,P=0.00).ANA的滴度与AnuA的浓度呈正相关(r=0.30,P=0.00),与抗dsDNA抗体的滴度无相关性(r=0.19,P=0.08),与抗dsDNA-NcX抗体的浓度呈正相关(r=0.50,P=0.00).红细胞沉降率在抗dsDNA-NcX抗体、抗dsDNA抗体阴性和阳性组间比较差异无统计学意义(x2=0.76,P=0.38;x2=0.13,P=0.18),而在AnuA阴性与阳性组间比较差异有统计学意义(x2 =20.31,P=0.00).CRP及24小时尿蛋白定量在三者阴性与阳性组间比较差异无统计学意义.补体C3、C4在AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体的阴性与阳性组间比较差异有统计学意义(x2=9.84,P=0.00;x2=16.53,P=0.00;x2 =10.33,P=0.00;x2 =11.61,P=0.00;x2 =12.69,P=0.00;x2=8.77,P=0.00).胱抑素在抗dsDNA抗体和AnuA的阴性与阳性组间比较差异无统计学意义,而在抗dsDNA-NcX抗体阴性与阳性组间比较差异有统计学意义(x2 =4.04,P=0.04).结论 抗dsDNA-NcX抗体可作为SLE的特异性抗体之一,其敏感性和特异性均高于抗dsDNA抗体和AnuA,三者均与SLE的疾病活动相关,联合检测有助于评估病情.     

抗促红细胞生成素受体抗体与系统性红斑狼疮伴贫血的相关性研究

目的 分析抗促红细胞生成素受体(EPOR)抗体在系统性红斑狼疮(SLE)中的作用,并探讨其与SLE伴贫血及病情的相关性.方法 应用酶联免疫吸附试验(ELISA)检测124例SLE患者中的抗EPOR抗体,并与7例自身免疫溶血性贫血,19例缺铁性贫血患者及45名健康人对照.同时分析SLE患者临床特点及病情活动度.所有计数资料采用x2检验或Fisher精确检验,计量资料采用t检验.结果 抗EPOR抗体在SLE组中发生率为20.2%,明显高于健康对照组的2.2%(P=0.004),而在自身免疫溶血性贫血及缺铁性贫血患者未检测到抗EPOR抗体.51例伴发贫血的SLE患者中,17例(33%)抗EPOR抗体阳性,而73例无贫血患者中仅有8例(11%)抗EPOR抗体阳性,差异有统计学意义(P=002);进一步分析发现抗EPOR抗体阳性患者其贫血程度重,而且呈现小细胞性贫血(P=0.005).对照抗EPOR抗体阳性与阴性患者的临床资料显示,皮疹(P=0.014)、补体C3下降(P=0.01)、抗dsDNA抗体阳性(P=0.000)及疾病活动积分高的SLE患者更易产生抗EPOR抗体.结论 抗EPOR抗体可能在SLE发生贫血的过程中起重要作用.ELISA测定抗EPOR抗体具有良好的稳定性和特异性,在伴发贫血的SLE患者中检测该抗体具有一定的临床价值.

Abstract：

Objective To investigate the presentationand significance of circulating autoantibodies to erythropoietin receptor (EPOR) in sera from patients with systemic lupus erythematosus (SLE). Methods One hundred and twenty-four consecutive patients with SLE, seven with autoimmune hemolytic anemia (AIHA), 19 patients with iron deficiency anemia (IDA) and 45 normal individuals were involved in this study. In all patients with SLE, the disease activity was evaluated using the European consensus Lupus Activity Measurement scale. Antibodies to EPOR were detected by enzyme-linked immunosorbent assay (ELISA). All data were tested with Chi-squared or Student's t tests by SPSS software. Results A higher frequency of antibodies to EPOR were detected in SLE patients than healthy controls (20.2% vs 2.2%, P=0.004), however, they could not be detected in AIHA and IDA patients. Moreover, anti-EPOR antibodies were detected in 17 (33.3%) of 51 SLE patients with anemia, compared with that in 8 (11.0%, P=0.002) of 73 patients without anemia. Furthermore, patients with antibodies to EPOR had more severe anemia and often presented as microcytic anemia (P =0.005) than those without anti-EPOR antibodies. Finally, anti-EPOR antibodies seemed to be more likely to occur in patients with skin rash (P=0.014), low levels of C3 component of complement (P=0.01), positive anti-dsDNA antibodies (P=0.000) and higher disease activity scores (P= 0.024). Conclusion The higher incidence of antibodies to EPOR in SLE patients with anemia suggest that anti-EPOR antibodies might play a vital role in the development of anemia in SLE patients. Thus, detecting anti-EPOR antibodies in SLE patients with anemia may be helpful.     

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。     

肺炎衣原体和巨细胞病毒感染与颈动脉粥样硬化斑块及其稳定性的相关性

目的 探讨颈动脉粥样硬化的发生与肺炎衣原体(Chlamydia pneumonia,Cpn)和巨细胞病毒(cytomegalovirus,CMV)两种微生物感染的相关性.方法 纳入颈动脉彩超显示内膜-中膜厚度(intima-media thickness,IMT)＞1.5 mm的患者作为颈动脉粥样硬化组,而IMT＜ 1.0 mm的健康体检者作为对照组.采用酶联免疫吸附法检测血清抗Cpn和抗CMV IgG抗体水平和阳性率.比较颈动脉粥样硬化组与对照组的人口统计学、血管危险因素以及抗Cpn和抗CMV IgG抗体阳性率.结果 颈动脉粥样硬化组共纳入患者92例,其中稳定斑块患者30例,不稳定斑块患者62例;对照组共纳入49例健康体检者.颈动脉粥样硬化组年龄以及男性、高血压、糖尿病、高脂血症和吸烟患者的构成比与对照组均无显著性差异(P均＞0.05).颈动脉粥样硬化组抗Cpn IgG(69.5％对26.5％彩=23.887,P＜0.001)、抗CMV IgG(75.0％对30.6％;x2 =26.156,P＜0.001)阳性率以及抗Cpn IgG+抗CMV IgG阳性率(51.2％对10.2％;x2 =24.006,P＜0.001)均显著性高于对照组.在颈动脉粥样硬化组中,不稳定斑块亚组年龄以及男性、高血压、糖尿病、高脂血症和吸烟患者的构成比与稳定斑块亚组均无显著性差异(P均＞0.05).不稳定斑块亚组抗Cpn IgG(80.6％对46.7％;x2=11.025,P=0.001)和抗CMV IgG(83.9％对56.7％;x2=7.980,P=0.005)阳性率以及抗Cpn IgG+抗CMV IgG阳性率(44.6％对7.6％;x2=10.210,P=0.006)显著性高于稳定斑块亚组.结论 颈动脉粥样硬化的发生和斑块稳定性均与Cpn和CMV感染相关,Cpn和CMV感染可能是颈动脉粥样硬化发生和斑块不稳定的重要因素.     

血清抗氨酰tRNA合成酶抗体检测在特发性炎性肌病伴间质性肺疾病中的意义

目的 检测多发性肌炎/皮肌炎患者血清抗氨酰tRNA合成酶(ARS)抗体水平,并与抗Jo-1抗体相比较,探讨其在特发性炎性肌病伴间质性肺疾病(ILD)中的意义.方法 采用酶联免疫吸附试验(ELISA)法测定109例多发性肌炎/皮肌炎患者,20例系统性红斑狼疮(SLE)患者,20例类风湿关节炎(RA)患者以及30名健康对照组血清中抗ARS抗体水平及阳性率.使用t检验、Mann-Wittney U检验、X2检验及Fisher精确检验分析ARS阳性患者的临床特点.使用McNemar检验比较抗ARS抗体和抗Jo-1抗体对诊断多发性肌炎/皮肌炎合并ILD的敏感性及特异性.结果 血清抗ARS抗体的阳性率在合并ILD的多发性肌炎/皮肌炎组、未合并ILD的多发性肌炎/皮肌炎组、SLE组、RA组及健康对照组分别是37.9％、7.8％、10％、0和0.合并ILD的多发性肌炎/皮肌炎组血清抗ARS抗体阳性率较未合并ILD的多发性肌炎/皮肌炎组、SLE组、RA组和健康对照组均显著升高(X2-13.5,5.45,10.57,15.17;P＜0.01).抗ARS抗体诊断多发性肌炎/皮肌炎合并ILD的敏感性显著高于抗Jo-1抗体(37.9％比17.2％,P＜0.01),而两者特异性差异无统计学意义(P＞0.05).抗ARS抗体阳性患者发热、ILD发生率较抗ARS抗体阴性患者显著升高(X2=12.55,13.53;均P＜0.01),而披肩征及向阳疹的发生率则低于ARS阴性组(X2=5.7,5.8;P均＜0.05).抗ARS抗体阳性组同抗Jo-1抗体阳性组间临床特点差异无统计学意义(P均＞0.05).随访发现多发性肌炎/皮肌炎合并ILD死亡患者血清抗ARS抗体均为阴性.结论 相较抗Jo-1抗体而言,血清抗ARS抗体检测对多发性肌炎/皮肌炎伴ILD的诊断敏感性更高,有利于早期诊断,值得临床推广应用.     

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.     

Less disease severity and favorable prognosis are associated with postmenopausal systemic lupus erythematosus patients

The aim of this study is to characterize the clinical manifestations of postmenopausal systemic lupus erythematosus (SLE) patients. Of the 699 SLE inpatients, 20 postmenopausal and 70 menstruous SLE patients were evaluated and compared for the clinical manifestations. The mean age of onset was 55.05 years (range from 42 to 66) with a peak of 50-60 in postmenopausal lupus patients. The average time from SLE onset to diagnosis was 2.18 years. Arthritis was the most frequent initial manifestation in the postmenopausal group. Other common clinical manifestations and laboratory abnormalities include lassitude, fever, alopecia, malar rash, cardiac impairment and weight loss, and elevated ESR, decreased C3, ANA >/= 1:80, hypergammaglobulinemia and anti-RNP antibody positive. Compared with menstruous lupus patients, postmenopausal patients were more likely to have weight loss (P < 0.01), myalgia and myasthenia (P < 0.01), and less likely to have malar rash (P < 0.05), renal involvement (P < 0.01), leukocytopenia (P < 0.05) and positive ANA (P < 0.01). Thus, less disease severity and favorable prognosis were associated with postmenopausal SLE patients. Misdiagnosis and missed diagnosis were easy to make with their non-specific symptoms with fewer features suggestive of diagnosis.     

Classification of an intermediate group of patients with antiphospholipid syndrome and lupus-like disease: primary or secondary antiphospholipid syndrome?

OBJECTIVE: (1) To classify an intermediate group of patients (IntAPS) with antiphospholipid syndrome (APS) and lupus-like disease either as primary (PAPS) or secondary APS (SAPS) and to discuss 2 different classifications. (2) To compare patients of a division of rheumatology with either PAPS or SAPS. METHODS: Patients with APS and patients with systemic lupus erythematosus (SLE) followed at the Department of Rheumatology, University Hospital Bichat, Paris, from 1987 to 1996 were analyzed. A chart review and a standardized telephone interview in 1997 completed the data of this study. RESULTS: (1) We found a total of 108 patients with APS: 22 with PAPS, 69 with SAPS, and 17 with IntAPS. The group of IntAPS did not differ from PAPS in any clinical or laboratory signs with the exception of antibodies to dsDNA and to extractable nuclear antigen (ENA). Between IntAPS and SAPS, there were several significant differences in clinical signs of SLE (malar rash, discoid rash, arthralgia) and in laboratory values (leukocytopenia). (2) Comparison of PAPS and SAPS showed statistically significant differences for positive Coombs' test, leukocytopenia, lymphocytopenia, antinuclear antibodies, antibodies to dsDNA and to ENA, and hypocomplementemia. CONCLUSION: The mainstay of the diagnosis of APS is the clinical event of thrombosis or miscarriage in the presence of antiphospholipid antibodies. Less important are laboratory values, which may help to differentiate PAPS from SAPS in order to initiate adequate therapy (e.g., anticoagulation in the first and additional corticosteroids in the second). Patients with IntAPS are more likely to be integrated into the group of PAPS than in the group of SAPS; therefore, special exclusion criteria for PAPS are not appropriate.     

Systemic lupus erythematosus in Tunisia: demographic and clinical analysis of 100 patients

There is a wide variation in the natural history of systemic lupus erythematosus (SLE) among different ethnic and geographical groups. Studies in Arabs are few and those in North Africans and especially in the Tunisian population do not exist. This study aims to demonstrate the demographic, clinical and laboratory characteristics of SLE Tunisian patients and to identify those at high risk for renal and neuropsychiatric involvements. One hundred patients with SLE (American College of Rheumatology criteria), seen at the Department of Internal Medicine of the University Hospital La Rabta in Tunisia over a 15-year period (1987 to 2001) were retrospectively enrolled. There were 92 women and eight men with an average age at the onset of disease of 32 years. Nineteen patients were aged over 50 years at the moment of SLE diagnosis (late-onset SLE). Of the patients, 78% had articular involvement, 53% photosensitivity and 63% malar rash. Serositis occurred in 45 patients of whom 16 had pericarditis and 29 had pleuritis. Nephritis was diagnosed in 43% of the cases and consisted always of glomerular nephritis, in three cases of which tubulointerstitial lesions were also observed. Comparison of patients with and without renal involvement showed that lupus nephritis was significantly associated with pericarditis (P = 0.03), arterial blood hypertension (P < 0.0001), cryoglobulinemia (P = 0.07) and antiphospholipid syndrome (P = 0.03). The SLEDAI at SLE diagnosis was significantly higher for lupus nephritis patients. Twelve patients with lupus nephritis died compared with three patients in the remaining group (P < 0.0001). Neuropsychiatric manifestations were observed in 25% of the cases. The mean age at SLE onset was significantly lower, the mean SLEDAI at SLE diagnosis and the mortality were significantly higher in the neuropsychiatric group than in the remaining group. Immunological features included antinuclear antibodies (100%), anti-DNA antibodies (56%), anti-Sm antibodies (61%), anticardiolipin antibodies (62%), anti-beta2GP1 (13%) anti-Rnp (23%) and hypocomplementemia (48%). The frequencies of pulmonary hypertension (25 versus 2%, P < 0.00001) and vascular thrombosis (25 versus 2%, P < 0.00001) were significantly higher in patients with positive anti beta2GP1 antibodies. The five-year survival rate in our series was 86%. The most frequent causes of death were active SLE and infections.     

Systemic lupus erythematosus in Aborigines and Caucasians in central Australia: a comparative study.

The objective of this study was to determine whether there are differences in the prevalence, clinical and laboratory manifestations, and morbidity and mortality of systemic lupus erythematosus (SLE) between Aborigines and Caucasians in Central Australia. The medical records of all patients diagnosed with SLE upto December 1999 were reviewed retrospectively. Prevalence of SLE was 1:1360 for Aborigines and 1:5170 for Caucasians. The prevalences of malar rash, discoid rash, photosensitivity, oral ulcers, pleuritis, anticardiolipin antibodies and lupus anticoagulant were higher in Caucasians than in Aborigines. The prevalences of anti-Sm antibody and anti-RNP antibody were higher in Aborigines than in Caucasians. These differences did not attain statistical significance. There was a low prevalence of renal disease in Aborigines and Caucasians. Mortality was low in Aborigines and nil in Caucasians. Although there is a high prevalence of SLE in Aborigines in Central Australia, renal involvement and mortality are low.     

Therapeutic Selective Adsorption of Anti-DNA Antibody Using Dextran Sulfate Cellulose Column (Selesorb) for the Treatment of Systemic Lupus Erythematosus

Abstract: The Selesorb therapeutic dextran sulfate cellulose column (Kaneka Corporation, Osaka, Japan) selectively adsorbs anti-DNA antibody, anti-cardiolipin antibody, and immune complex from the plasma of patients with systemic lupus erythematosus (SLE). The Selesorb system is composed of twin columns attached to an automated regeneration apheresis unit. Anti-DNA antibody in plasma is continuously removed through 1 of the 2 columns alternately. Clinical application of the Selesorb system to SLE patients with high titers of anti-DNA antibody showed improvement of proteinurea, arthralgia, rash, lymphocytopenia, etc., with the concurrent use of steroid and/ or immnosuppressant. Angiotensin converting enzyme inhibitor should not be administered to patients treated with the Selesorb system to avoid anaphylactoid reactions based on rapid increases of bradykinin concentrations in the blood. Abstract: The Selesorb system removed anti-DNA antibody, anticardiolipin antibody and immune complex from the plasma of SLE patients. Other biochemical parameters such as total protein and albumin remained at almost the same levels as before apheresis. The efficiency of the removal of anti-DNA antibody was maintained during the treatment using the 2 adsorbent columns with alternate use of adsorption and regeneration using the automated apheresis unit MA-01. Clinical manifestations such as proteinurea, arthralgia, rash, lymphocytopenia, etc., were improved under concomitant use of conventional immunosuppressants during Selesorb treatments. Care should be taken not to administer ACE inhibitor to patients treated with the Selesorb column to avoid anaphylactoid reactions.     

Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study.

To determine whether an association exists between the presence of antiphospholipid antibodies and pregnancy loss, a cross-sectional study was performed. Consecutive women who were referred to three outpatient rheumatology clinics and who had systemic lupus erythematosus (SLE) and a history of one or more pregnancies were evaluated. Patients were interviewed to determine outcomes of all previous pregnancies. Blood was taken on two separate occasions at least 3 months apart to test for the presence of the lupus anticoagulant and anticardiolipin antibodies; on both occasions, five tests of the lupus anticoagulant, with well-defined normal ranges, and an enzyme-linked immunosorbent assay to measure IgG anticardiolipin antibodies were performed. Patients were considered to be positive for the lupus anticoagulant if one or more tests was abnormal on both occasions and positive for anticardiolipin antibodies if the test was abnormal on both occasions. Forty-two women were studied. Statistically significant associations were shown between lupus anticoagulant positivity and previous pregnancy loss (odds ratio [OR], 4.8; 95% confidence intervals [CI], 1.0 to 23.6; P = .05) and between anticardiolipin antibody positivity and previous pregnancy loss (OR, 20.0; 95% CI, 1.3 to 97.0; P = .01). All seven women with multiple episodes of pregnancy loss were lupus anticoagulant positive and four of these were also anticardiolipin antibody positive. If patients who are transiently positive for lupus anticoagulant and/or anticardiolipin antibodies are considered to be test positive, the associations with pregnancy loss are no longer statistically significant. Within the group of lupus anticoagulant-positive patients, we observed stronger associations between the presence of six or more positive tests and pregnancy loss than between the presence of two to five positive tests and pregnancy loss. No single test for the lupus anticoagulant provides a statistically significant association with pregnancy loss. The results of our study show that by performing multiple lupus anticoagulant tests and by repeating testing for lupus anticoagulant and anticardiolipin antibodies on more than one occasion, significant associations between the presence of antiphospholipid antibodies and previous pregnancy loss can be shown in patients with SLE.     

维生素D受体起始密码子基因多态性与系统性红斑狼疮相关性研究

目的 检测维生素D受体(VDR)基因多态性在系统性红斑狼疮(SLE)患者中的分布,探讨其与SLE发病的相关性.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测VDR起始密码子(FokI)多态性位点和基因型在271例SLE患者和130名健康对照组中的分布情况.采用χ2检验和方差分析进行统计学处理.结果 SLE患者及健康对照组VDR FokI多态性基因型和等位基因分布均不处于Hardy-Weinberg平衡(SLE组χ2=7.883,P=0.019;健康对照组:χ2=7.288,P=0.026).VDR FokI多态性等位基因F和f的分布频率在健康对照组分别为48.8%和51.2%,在SLE组分别为60.9%(χ2=10.39,P=0.001)和39.1%(χ2=10.39,P=0.001);F等位基因个体发生SLE的比值比(OR)为1.630(95%CI=1.210～1.1%,χ2=10.39,P=0.001).基因型FF、Ff和ff分布频率在健康对照组中分别为25.4%、46.9%和27.7%,在SLE组中分别为42.8%(χ2=11.417,P=0.001)、36.2(χ2=4.251,P=0.039)和21.0%(χ2=2.187,P=0.139);FF和Ff基因型个体发生SLE的OR分别为2.200(95%CI=1.385～3.493,χ2=11.417,P=0.001)和0.641(95%C1=0.419～0.979,χ2=4.251,P=0.039).进一步分析发现,不同VDR FokI多态性基因型SLE患者之间疾病活动性积分(SLEDAI)差异无统计学意义(P=0.382).但与FF和ff基因型SLE患者对照,Ff基因型SLE患者中浆膜炎的发生率更高(P=0.001),而且具有更高阳性率的抗双链DNA(dsDNA)抗体(P=0.001)、抗Sm抗体(P=0.047)和抗组蛋白抗体(P=0.001),但皮疹发生率较低(P=0.005).结论 VDR FokI多态性位点F等位基因和F/F及F/f基因型与SLE发病易感性有关,而且F/f杂合子患者更容易发生浆膜炎和产生抗dsDNA抗体、抗Sm抗体和抗组蛋白抗体.     

Association of anti-DNA idiotype markers with clinical and serological manifestations in patients with systemic lupus erythematosus

Serum levels of 6 anti-DNA antibody idiotypes were measured in 65 consecutive patients with systemic lupus erythematosus (SLE) and 45 healthy subjects. Five of the 6 idiotypes were elevated in SLE sera compared to the normal controls (p less than 0.005). Analysis of the associations of the idiotypes with clinical, hematological, and serological characteristics revealed that significantly decreased serum levels of 3 idiotypes (103.1, 100, and 1305) were associated with nephritis and that one of these idiotypes (103.1) was also associated with discoid rash. An association of lowered levels of 3 idiotype markers (604, 1305, and 1400) was also observed with the presence of lupus anticoagulant and anticardiolipin antibodies. Serial studies in individual patients with SLE nephritis failed to show a close correlation of serum idiotype levels with the degree of proteinuria, creatinine clearance, anti-DNA antibody, or complement values. The association of decreased levels of specific idiotypes with the presence of nephritis, discoid rash, and antiphospholipid antibodies suggests the participation of these antibodies in the pathogenesis of disease.     

Anti-oxidized low-density-lipoprotein (OxLDL) antibodies in systemic lupus erythematosus with and without antiphospholipid syndrome

The aim of this study was to examine potential links between antiOxLDL antibodies and the clinical and biological features of secondary antiphospholipid syndrome (II APLS) associated with systemic lupus erythematosus (SLE). A cohort study was done of 98 SLE patients followed-up for 1 y, including 18 with definite II APLS and 13 patients with definite primary APLS (I APLS). IgG anticardiolipin, IgG anti beta2 GPI, lupus anticoagulant, VDRL and IgG antiOxLDL were measured in all 98 study subjects. High antiOxLDL titers were found in seven (39%) of the 18 patients with II APLS vs 10 (12.5%) of the 80 patients without APLS (P < 0.01; OR = 4.45; 95% CI = 1.4-14.1) and none of the 13 patients with I APLS (P < 0.02). The mean antiOxLDL titer was not significantly higher in the SLE patients with than without II APLS (P > 0.05). A high antiOxLDL titer was correlated with deep venous thrombosis (P < 0.01; OR = 5.77; 95% CI = 0.54-61) but not with arterial thrombosis (P > 0.05; OR = 1; 95% CI = 0.29-3.09), thrombocytopenia, central nervous system involvement, livedo reticularis, or a positive Coombs test. The antiOxLDL antibody titer was correlated with the IgG anticardiolipin antibody titer (r = 0.235; P = 0.02) and with the IgG anti-beta2 GPI antibody titer (r = 0.224; P = 0.026). AntiOxLDL elevation was found in 17% of SLE patients and was significantly associated with II APLS and venous thrombosis. We found no evidence suggesting that antiOxLDL may be associated with atherosclerosis.