Immunosuppression in pregnant women with systemic lupus erythematosus

Most pregnancies are successful in women with systemic lupus erythematosus, particularly if the disease is quiescent and there are no signs of active nephritis. There is no major impact of immunosuppression on maternal outcome. However, high doses of cyclosporine and glucocorticoids are used which may favor development of hypertension or preeclampsia. Some immunosuppressive drugs may exert toxic effects on the fetus. Glucocorticoids may cause small birth weight, and azathioprine and calcineurin inhibitors may be associated with lower birth weight, gestational age and prematurity. Cyclophosphamide may cause fetal malformation when given in the first trimester. Mycophenolate and leflunomide are teratogenic drugs and should be withdrawn before conception in case of programmed pregnancy or should be rapidly discontinued in case of unexpected pregnancy. Option counseling for pregnancy and correct use of immunosuppressive drugs are prerequisites for a successful pregnancy in women with lupus.     

血清泌乳素与系统性红斑狼疮患者肾损害的相关性

目的: 探讨系统性红斑狼疮（SLE）患者血清PRL水平与肾损害的相关性。方法： 应用免疫放射量度分析法检测80例SLE患者血清PRL水平并分析其与肾受累的关系。 结果： 高泌乳素血症者肾受累发生率明显高于PRL水平正常者，血清PRL水平与SLEDAI评分、抗ds-DNA抗体滴度、24 h尿蛋白定量、尿微量白蛋白定量（MA）、尿转铁蛋白定量（MTF）、尿免疫球蛋白定量（Ig）及肾脏病理活动指数呈正相关，与血清白蛋白(ALB)水平呈负相关。Logistic 回归分析显示肾受累与血清PRL水平增高及C3水平降低有关。结论： 血清PRL水平升高与SLE肾脏受累有关，其检测可作为肾脏受累的监测指标之一。     

重建系统性红斑狼疮治疗与创面修复的平衡

复习目前国内外关于系统性红斑狼疮合并皮肤溃疡的病例报道及基础研究,探讨系统性红斑狼疮合并皮肤溃疡的临床特点及治疗方法.皮肤溃疡的严重程度不仅与局部创面相关,同时也与全身病情严重程度密不可分,对于此类皮肤溃疡需要多学科协作,定期评估创面局部情况与全身病情进展程度,及时调整治疗方案,寻找控制病情与创面修复的平衡点.     

中国南方系统性红斑狼疮患者Fas-670基因多态性研究

目的:研究Fas-670基因多态性在中国南方地区汉族人群中的分布及其与系统性红斑狼疮(SLE)的相关性。方法:应用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)方法,对103例SLE患者和110例中国南方地区汉族正常对照者进行了Fas-670基因多态性检测。结果:SLE患者Fas基因-670位点基因型和等位基因频率与正常对照组比较无显著差异;而Fas基因-670位点基因型和等位基因频率分布,按性别分层后,男性和女性SLE患者分别与正常对照者比较以及SLE并发狼疮性肾炎(LN)患者和正常对照组比较及SLE并发LN患者与未并发LN患者间比较,均无显著差异。结论:Fas-670基因多态性与中国南方地区汉族系统性红斑狼疮无相关性。     

The expression of PD-1 and level of CXCL10 in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is known tobe a chronic and complicated rheumatic diseasewith an autoimmune etiology.SLEis also a proto-type of autoimmune disease due to a substantialoverlapinits clinical symptoms withother autoim-mune diseases . The immune systemof SLElosesbalance of auto-tolerance ,in which lymphocytesare activated excessively,contributingto SLE de-velopment .It has been well established that effi-cient T cell-mediated immune responses requirenot only the TCR-mediat…     

系统性红斑狼疮患者骨髓间充质干细胞细胞因子分泌及其与病情活动的相关性研究

目的 探讨系统性红斑狼疮（SLE）患者骨髓间充质干细胞（MSCs）细胞因子分泌及其与疾病活动的相关性.方法 采用密度梯度离心和贴壁分离法对11例SLE患者和6例正常人骨髓MSCs进行分离培养,流式细胞术鉴定MSCs.取P2代细胞,半定量RT-PCR检测SLE患者骨髓MSCs白细胞介素-6（IL-6）,IL-7,IL-11,巨噬细胞集落刺激因子（M-CSF）和干细胞因子（SCF）的表达.结果 SLE患者MSCs均表达CD29、CD44和CD105,不表达CD14、CD34、CD45和HLA-DR.两组P2代MSCs均表达IL-6、IL-7、IL-11、M-CSF和SCF.SLE患者组MSCs IL-6、IL-7表达降低（P＜0.01）,IL-7的表达和SLE的活动评分（SLEDAI）呈负相关（r=-0.891,P＜0.05）.结论 SLE患者MSCs细胞因子分泌异常,可能与SLE血液系统损害及病情活动相关.     

定量蛋白质组学技术构建系统性红斑狼疮疾病的蛋白质组差异表达图谱

目的: 应用定量蛋白质组学技术对系统性红斑狼疮(SLE)病人外周血单个核细胞中的"全组"蛋白进行鉴定和定量分析,获得SLE的蛋白质组差异表达图谱。方法: 利用基于四重相对和绝对定量的等量异位标签结合多维液相色谱-串联质谱分析SLE稳定期和活动期病人以及类风湿关节炎病人和健康人的外周血单个核细胞总蛋白,用肽质量指纹谱经数据库检索鉴定蛋白质,并比较这些蛋白的表达差异。结果: 共鉴定了400多个蛋白质。其中,与健康对照组相比,SLE稳定组和SLE活动组共发现2倍以上表达差异的蛋白质44个,上调的9个,下调的35个;与类风湿关节炎疾病组相比,SLE稳定组和SLE活动组2倍以上表达差异的蛋白共有52个,上调的19个,下调的33个;SLE活动组与SLE稳定组相比,表达上调和下调的蛋白分别为17个和13个。结论: 定量蛋白质组学技术可有效地用于人外周血单个核细胞蛋白鉴定和相对定量;采用该技术获得了SLE病人外周血单个核细胞的蛋白质组差异表达图谱;深入研究这些蛋白的分子机制将有助于进一步阐明SLE的发病机制,为SLE的诊断和治疗提供新途径。     

系统性红斑狼疮患者血清IL-10的水平及临床意义

目的 观察系统性红斑狼疮(systemic lupus erythematosus,SLE)患者血清IL-10的表达与疾病活动的关系.方法 选取22例SLE患者及24名健康人作为对照,根据狼疮疾病活动指数(SLE disease activity index,SLEDAI)将SLE患者分为活动期组和非活动期组,检测血清抗dsDNA抗体,血清总补体溶血活性(CH50)及C反应蛋白(C reactive protein,CRP),酶联免疫吸附法(ELISA)检测血清IL-10表达.结果 与对照组[(18.11±6.97)ng/L]相比,IL-10在SLE活动期组[(78.54±5.62)ng/L,P＜0.01]及非活动期组[(30.36±10.98)ng/L,P＜0.05]均有所增高,活动期组增高更为明显(与非活动期组相比,P＜0.05).IL-10水平与SLEDAI呈正相关(SLE活动期,r=0.77,P＜0.01;SLE非活动期,r=0.84,P＜0.01),IL-10的水平与抗dsDNA抗体(r=0.71,P＜0.01)、CRP(r=0.63,P＜0.01)和CH50(r=-0.56,P＜0.05)均相关.结论 IL-10在SLE患者血清中表达升高,在疾病活动时更为明显,IL-10能反应疾病活动的程度,可以做为临床观察SLE疾病活动的指标之一.     

系统性红斑狼疮患者血清IL-10的水平及临床意义

目的观察系统性红斑狼疮(systemic lupus erythematosus,SLE)患者血清IL-10的表达与疾病活动的关系。方法选取22例SLE患者及24名健康人作为对照,根据狼疮疾病活动指数(SLE disease activity index,SLEDAI)将SLE患者分为活动期组和非活动期组,检测血清抗dsDNA抗体,血清总补体溶血活性(CH50)及C反应蛋白(C reactive protein,CRP),酶联免疫吸附法(ELISA)检测血清IL-10表达。结果与对照组[(18.11±6.97)ng/L]相比,IL-10在SLE活动期组[(78.54±5.62)ng/L,P<0.01]及非活动期组[(30.36±10.98)ng/L,P<0.05]均有所增高,活动期组增高更为明显(与非活动期组相比,P<0.05)。IL-10水平与SLEDAI呈正相关(SLE活动期,r=0.77,P<0.01;SLE非活动期,r=0.84,P<0.01),IL-10的水平与抗dsDNA抗体(r=0.71,P<0.01)、CRP(r=0.63,P<0.01)和CH50(r=-0.56,P<0.05)均相关。结论IL-10在SLE患者血清中表达升高,在疾病活动时更为明显,IL-10能反应疾病活动的程度,可以做为临床观察SLE疾病活动的指标之一。     

Atherosclerosis in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease that has a late mortality phase owing mainly to cardiovascular manifestations. Atherosclerosis itself is characterized by inflammatory components, fulfilling the criteria of Witebsky and Rose for an autoimmune disease. SLE patients have increased risk for cardiovascular events, and these are the result of both atherosclerosis and thromboembolic events. Risk factors for atherosclerosis in SLE include “traditional” risk factors (mainly the Framingham risk factors), as well as disease-related factors including disease duration, steroid therapy, and renal disease, and inflammatory mechanisms that specifically contribute to enhanced atherosclerosis in SLE. These include specific antibodies to β2GPI; anticardiolipin antibodies; anti-oxidized low-density lipoprotein; and antibodies to heat shock proteins, complement activation, impaired ability to activate TGF-β1, and elevated levels of CRP. These findings stress the importance of surveillance and preventive strategies to control atherosclerosis in SLE.     

DNA甲基化与系统性红斑狼疮

系统性红斑狼疮是一种针对自身抗原产生自身抗体从而形成免疫复合物为特征的慢性炎症性的自身免疫性疾病,能够累及机体的多个脏器(以皮肤、关节、肾脏受累为多见).系统性红斑狼疮的发病机制涉及到环境、遗传、性别多个因素的相互作用,对于哪个因素在其中起着关键性的作用,是如何诱发疾病的发生,以及在发病过程中的具体作用机制到目前来说还没有一个统一认识.目前许多研究表明,DNA的甲基化可以作为环境、性别等因素的共同作用通路在狼疮的发病中起到一定的作用,现就关于DNA的甲基化与系统性红斑狼疮的关系做一综述.     

系统性红斑狼疮外周血单个核细胞CD40L的表达增高

目的:了解系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)的白细胞分化抗原40配体(CD40L)表达,探讨其在发病中的作用。方法:分离SLE患者和正常人PBMCs,采用流式细胞术,检测其在正常状况和应用植物凝集素(PHA)及地塞米松(Dex)后,CD40L的表达水平,并进行比较;分析SLE患者CD40L的表达水平和狼疮活动指数(SLEDAI)的相关性。结果:活动期SLE患者PBMCs的CD40L阳性细胞百分率(%)明显高于对照组,且高于静止期SLE患者;应用PHA处理24h后,3组PBMC表达CD40L均明显增加,但活动期SLE患者增加更明显;应用地塞米松后,SLE患者(活动期和静止期)PBMCs的CD40L表达明显减少,对照组无明显改变;SLE患者(活动期和静止期)CD40L的表达水平和SLEDAI均呈明显正相关。结论:CD40L在SLE患者PBMCs的表达增加,和疾病活动度有关;其受PHA和Dex调控,在SLE发病和病程中起重要作用。     

全身性红斑狼疮病人C4基因组DNA限制性片段长度多态性的检测

以Ｃ４基因５＇ｃＤＮＡ片段为探针，经Ｓｏｕｔｈｅｒｎ印迹杂交法对２４例全身性红斑狼疮（ＳＬＥ）病人基因组ＤＮＡ的Ｃ４基因限制性片段长度多态性（ＲＦＬＰ）进行了分析，并与６０例健康人资料进行了对比。结果显示，ＳＬＥ病人Ｃ４Ａ基因缺失的表型频率与基因型频率远较健康人为高，分别为２９．２％对６．７％（Ｘ＾２＝７．７５，Ｐ＜０．０１）及１８．７％对３．３％（Ｘ＾２＝１０．８，Ｐ＜０．００５）。在两名同合子     

系统性红斑狼疮患者可溶性血管细胞间粘附分子-1的变化

目的：了解系统性红斑狼疮（SLE）患者血清中可溶性血管细胞间粘附分子-1（sVCAM-1）水平以及同临床病情的关系。方法：应用ELISA双抗体夹心法测定血清中VCAM-1水平，同时检测其它免疫学指标。结果：活动期SLE患者sVCAM-1水平高于稳定期和健康人，抗双链DNA抗体（抗ds-DNA抗体）阳性者或伴狼疮性肾炎病人更高；sVCAM-1水平与血沉呈显著正相关。结论：sVCAM-1可以作为SLE活动和严重程度的血清学参数，SLE发病可能与自身抗体ds-DNA使血管内皮细胞活化有关。     

系统性红斑狼疮患者外周血单个核细胞中IL—4和IL—13 mRNA的表达

目的探讨Th2型细胞因子在系统性红斑狼疮(SLE)发病机制中的作用及其意义.方法应用逆转录-聚合酶链反应(RT-PCR)检测了34例活动期SLE患者和30例正常人外周血单个核细胞(PBMC)中IL-4和IL-13mRNA的表达水平.结果活动期SLE患者IL-4和IL-13的阳性表达率与正常人对照组相比均无明显差异(P>0.05);活动期SLE患者PBMC中IL-4和IL-13mRNA的平均表达水平(0.938 6±0.168 9,0.898 3±0.115 3)均明显高于正常人对照组(0.5494±0.151 0,0.608 5±0.090 3),差异非常显著(P<0.001).结论Th2型细胞因子IL-4和IL-13在SLE患者中呈高水平表达,这可能与SLE患者外周血T细胞高度活化、功能异常有关.     

Anti-mannose binding lectin antibodies in sera of Japanese patients with systemic lupus erythematosus

Mannose-binding lectin (MBL) is a key element in innate immunity with functions and structure similar to that of complement C1q. It has been reported that MBL deficiency is associated with occurrence of systemic lupus erythematosus (SLE). We hypothesized that anti-MBL antibodies, if present, would affect the occurrence or disease course of SLE, by reduction of serum MBL levels, interference of MBL functions, or binding to MBL deposited on various tissues. To address this hypothesis, we measured the concentration of anti-MBL antibodies in sera of 111 Japanese SLE patients and 113 healthy volunteers by enzyme immunoassay. The titres of anti-MBL antibodies in SLE patients were significantly higher than those in healthy controls. When the mean + 2 standard deviations of controls was set as the cut off point, individuals with titres of anti-MBL antibodies above this level were significantly more frequent in SLE patients (9 patients) than in controls (2 persons). One SLE patient had an extremely high titre of this antibody. No associations of titres of anti-MBL antibodies and (i) genotypes of MBL gene, (ii) concentrations of serum MBL, or (iii) disease characteristics of SLE, were apparent. Thus, we have confirmed that anti-MBL antibodies are indeed present in sera of some patients with SLE, but the significance of these autoantibodies in the pathogenesis of SLE remains unclear.     

炎性细胞因子在系统性红斑狼疮中的作用

系统性红斑狼疮是一个全身性自身免疫病，常伴多器官受累，许多炎性细胞因子参与了系统性红斑狼疮的发病与发展，该病的活动性及器官损伤程度与不同的细胞因子相关。     

New therapies for systemic lupus erythematosus

In the past 40 years, prognosis for patients with systemic lupus erythematosus (SLE) has improved, with 10-year survival now approximately 90%. This is due probably to a combination of earlier disease diagnosis and diagnosis of milder disease, due in part to availability of multiple serological tests for SLE, use of steroids and other immunosuppressive agents, and availability of renal dialysis and transplantation. Despite this, however, the potential for significant morbidity and mortality remains in the group of patients with partially responsive or treatment resistant disease. More recently, advancements in the understanding of molecular mechanisms involved in the pathogenesis of SLE have translated to the development of novel therapies, offering possible alternatives to this patient cohort. Discussion of these pharmacological options and ongoing research forms the basis of this review.     

T helper cell dysfunction in systemic lupus erythematosus (SLE): Relation to disease activity

Patients with systemic lupus erythematosus (SLE) are known to have defects in both humoral and cellular immunity. The significance of defective T cell-mediated immunity and its relationship to disease activity have not been clearly established. We studiedin vitro T helper cell (Th) function in 150 SLE outpatients and correlated Th function with validated measures of disease activity. Interleukin 2 (IL-2) production by peripheral blood mononuclear cells (PBMC) was measured after stimulation with the recall antigens influenza A virus (FLU) and tetanus toxoid (TET), irradiated allogeneic peripheral blood mononuclear cells (ALLO), and phytohemagglutinin (PHA). We observed three patterns of Th response: (1) 76 of 150 (50%) of patients responded to the recall antigens FLU and/or TET, ALLO, and PHA; (2) 62 of 150 (42%) of patients did not respond to recall antigens but responded to ALLO and PHA; and (3) 12 of 150 (8%) of patients did not respond to either recall antigens or ALLO antigens. This diminished T cell function was correlated with higher disease activity as measured by four scales of clinical activity, such that individuals who exhibited morein vitro immune dysfunction presented with significant increases in their clinical activity indicies. The alterations in T cell function could not be accounted for by medication doses alone. Thus, SLE patients have multiple distinct defects at the level of the Th cell which are associated with clinical measures of disease activity.     

抗核小体抗体与儿童系统型红斑狼疮的相关性

目的探讨抗核小体抗体（AnuA）在诊断儿童系统型红斑狼疮（SLE）中的敏感性和特异性，了解AnuA与儿童SLE临床特征、疾病活动性的相关性。方法用Hep-2细胞提取核小体。用酶联免疫吸附方法（ELISA）测定血清中的AnuA，分析AnuA和临床表现的相关性。结果52例SLE中18例AnuA阳性。27例疾病对照组中1例AnuA阳性，30例正常对照组AnuA均为阴性。AnuA在儿童SLE中的敏感性为35％，特异性为96％。AnuA阳性组SLE患儿100％有中枢神经系统损害，AnuA阴性组为47％（x^2=14．57，P〈0．05）。AnuA阳性组SLE患儿100％有肾脏损害，AnuA阴性组为5l％（x^2=13．31，P〈0．05）。AnuA阳性和AnuA阴性的SLE患儿SLEDAI评分高于10分者分别为100％和71％（x^2=6．56，P〈0．05）。结论AnuA对儿童SLE的诊断具有较高的特异性，有助于抗dsDNA抗体、抗心磷脂抗体阴性的儿童SLE的诊断。