系统性红斑狼疮患者血清蛋白质组学研究

目的 运用蛋白质组学的方法,分析正常人及SLE患者血清蛋白质的差异表达,寻找与SLE疾病发病机制相关的蛋白质.方法 分别收集健康人及SLE患者血清各9例,同组血清等量混合,用试剂盒除去血清中的白蛋白和免疫球蛋白,再经除盐浓缩后,将血清样品采用固相pH梯度（IPG）双向凝胶电泳（2-DE）分离正常人及SLE患者血清的总蛋白质.凝胶经考马斯亮蓝染色显色后,利用Analysis2d软件对获得的蛋白图谱进行分析,寻找差异表达的蛋白质,利用基质辅助激光解析电离飞行时间质谱（MALDI-TOF-MS）进行鉴定,分析差异蛋白点.结果 对照组凝胶共检出蛋白点648个,患者组检出639个.对照组凝胶蛋白点匹配率84.5％,患者组凝胶蛋白点匹配率82.5％.通过比较分析,差异表达蛋白质点数为92个,有52个蛋白点在SLE患者组表达上调,40个表达下调,有14个点的表达水平在组间差异有统计学意义,质谱鉴定共鉴定5个蛋白质.通过文献研究显示,我们鉴定的部分蛋白在SLE的发病机制中起潜在的作用.结论 在SLE患者血清中存在着差异血清蛋白质,这些蛋白质可能是SLE发病的内在因素,并且在SLE的疾病发展过程中发挥重要作用,可能作为新的血清标志物和潜在的自身抗原.     

抗内皮细胞抗体及内皮素在系统性红斑狼疮中的致病作用

目的：探讨抗内皮细胞抗体（ＡＥＣＡ）及内皮素（ＥＴ）与系统性红斑狼疮（ＳＬＥ）发病之间的关系。方法：采用ＥＬＩＳＡ法检测了４６例ＳＬＦ病人血浆中ＡＥＣＡ,并同步检测血浆内皮素水平。结果：发现活动期ＳＬＥ病人组ＡＥＣＡ阳性率明显较非活动期及正常对照组高,ＡＥＣＡ阳性的ＳＬＥ病人皮肤粘膜损害、浆膜炎、肾损害发生率较ＡＥＣＡ阴性病人明显增高,ＡＥＣＡ阳性组ＥＴ浓度也明显增高。结论：提示ＡＥＣＡ不仅直接参     

系统性红斑狼疮自身抗体研究进展

经化学修饰的组织抗原,与正常组织成分有交叉反应的外来抗原、隔绝的体内自身成分及低分化的组织抗原等在一定条件下可刺激机体组织产生自身抗体.某些自身抗体因对系统性红斑狼疮(SLE)的判断具有高度特异性,已成为诊断SLE的血清指标或特异性抗体,有些自身抗体与疾病的活动性有相关性.因此,测定自身抗体有助于SLE的诊断,并对疾病的活动程度,观察治疗效果,指导临床用药具有重要的临床意义.     

系统性红斑狼疮外周血淋巴细胞凋亡和循环中自身核抗原的关系

系统性红斑狼疮（ＳＬＥ）是一种针对自身细胞核抗原的免疫性疾病，其核抗原中最主要的包括核小体复合物，组蛋白和ＤＮＡ，细胞程序性死亡或凋亡的特征是将细胞核染色质裂解的寡聚核小体，然后将其释放到细胞外空间，这些核小体是否作为免疫原驱动自身免疫反应：ＳＬＥ患者外周血淋巴细胞凋亡是否与ＳＬＥ的发病有关，本文就ＳＬＥ细胞凋亡与自身抗原来源之间的关系作一综述。     

系统性红斑狼疮患儿血清抗内皮细胞抗体检测的临床意义

为探讨抗内皮细胞抗体(anti-endothelial cell antibody, AECA)在系统性红斑狼疮(systemic lupus erythematosus, SLE)患儿外周血中的表达情况及其临床意义,采用间接免疫荧光法(indirect immunofluorescence analysis, IIF)检测35例SLE患儿外周血IgG-AECA的表达情况。患儿中活动期20例、缓解期15例,另选取15例择期手术患儿作为对照组,观察比较各组患儿外周血血清中IgG-AECA的表达情况,同时检测上述35例SLE患儿外周血中抗dsDNA抗体的表达情况。将35例SLE患儿根据外周血中IgG-AECA的表达情况分为IgG-AECA阳性组和IgG-AECA阴性组,分别观察两组患儿免疫功能、炎症反应和凝血功能等各项检测指标间的差异以及继发狼疮性肾炎(lupus nephritis, LN)和尿微量蛋白的表达情况。结果显示,对照组儿童外周血IgG-AECA均为阴性,SLE患儿IgG-AECA的阳性率(51%)明显高于对照组(P0.05),且活动期SLE组患儿IgG-AECA的阳性率(70%)明显高于对照组(P0.05);SLE患儿外周血dsDNA的阳性率为40%,IgG-AECA和dsDNA联合检测的阳性率提高至69%;IgG-AECA阳性组SLE患儿外周血中IgA、IgM、IgG水平,sIL-2R、IL-6和TNF-α水平,纤维蛋白降解产物(fibrin degradation products, FDP)和D-二聚体水平以及尿微量蛋白表达水平均高于IgG-AECA阴性组(P0.05),而C4水平低于IgG-AECA阴性组(P0.05)。该研究提示IgG-AECA与SLE患儿疾病活动性密切相关,其可通过介导免疫功能紊乱参与SLE的发病过程,并可导致患儿肾脏功能损伤,对LN的诊断具有临床指导意义。     

系统性红斑狼疮外周血淋巴细胞凋亡和循环中自身核抗原的关系

系统性红斑狼疮（ＳＬＥ） 是一种针对自身细胞核抗原的免疫性疾病，其核抗原中最主要的包括核小体复合物、组蛋白和ＤＮＡ。细胞程序性死亡或凋亡的特征是将细胞核染色质裂解为寡聚核小体，然后将其释放到细胞外空间。这些核小体是否作为免疫原驱动自身免疫反应；ＳＬＥ患者外周血淋巴细胞凋亡是否与ＳＬＥ的发病有关，本文就ＳＬＥ细胞凋亡与自身抗原来源之间的关系作一综述。     

系统性红斑狼疮患者自身抗体检测及意义

目的：探讨自身抗体在系统性红斑狼疮（SLE）中的意义。方法：采用放射免疫分析检测50例SLE患者血清中的抗双链DNA（dsDNA）抗体,采用德国IMTEC公司抗核抗体谱线性印迹法检测抗核小体抗体（AnuA）、抗组蛋白抗体（AHA）、抗StuD1等其他自身抗体。结果：抗StuD1阳性率最高（82％）,其次是抗R060KD抗体（80％）和AunA（72％）;抗dsDNA、AHA、抗U1-RNP、抗R052KD、抗SSB的阳性率分别为44％、32％、58％、48％、24％。其他三种自身抗体阳性率很低。结论：SLE患者血清中可出现大量的自身抗体,同时检测多种自身抗体能提高对SLE的鉴别诊断。     

脐带间充质干细胞与系统性红斑狼疮

系统性红斑狼疮（SLE）是一种以免疫细胞活化和自身抗体产生为特征的自身免疫病。间充质干细胞（MSC）是属于中胚层的一类多能干细胞,不仅具有多向分化潜能,还有多种免疫调节作用。许多研究表明MSC对可以通过调节免疫细胞（上调Foxp3’T细胞水平、下调Th17细胞水平、抑制浆细胞的成熟等）的表达以及细胞因子（IL-10、TGF—β、TNF—α等）的分泌干预抑制SLE,并且免疫原性较低。尤其脐带MSC,因为其独特优势,目前已经成为干细胞干预治疗SLE的研究热点。     

系统性红斑狼疮中的树突状细胞相关研究进展

系统性红斑狼疮中T细胞的过度活化可能与树突状细胞功能失调有关。发现其前体单核细胞和浆细胞样细胞功能紊乱，SLE的血清中含有IFN-α的诱导物，可以促进正常单核细胞向树突状细胞的分化，髓样和淋巴样树突状细胞有异常迁移行为。树突状细胞的异常已经成为SLE中研究的一个新课题。     

脐带间充质干细胞与系统性红斑狼疮

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of immune cells and production of autoantibodies by plasma cells and release of cytokines. Mesenchymal stem cells (MSC) are widely studied as an alternative cell source for their ability to differentiate into multiple mesenchymal lineages. An important function for MSC for autoimmune diseases is their immunomodulatory effect on various activated lymphoid cells, such as T cells B cells, NK cells, and dendritic cells; and on cytokines , such as IL-10, TGF-β, TNF-α, et al. Umbilical cord MSCs (UC-MSCs) had a higher proliferation capacity and lower immunogenicity, indicating that it may be a novel alternative source of human MSC for clinical application. In this review, we introduce the immunomodulatory effect and clinical application of UC-MSC in SLE based on recent findings in human and animal models.     

T cells in the pathogenesis of systemic lupus erythematosus

Recent studies in patients with systemic lupus erythematosus (SLE) have demonstrated that autoantigen-reactive T cells can be isolated from peripheral blood and that such cells can support autoantibody production ex vivo, suggesting that they may have a central role in the pathogenesis of disease. In addition, recent work has identified and characterized signaling abnormalities in T cells from SLE that may be fundamental to the disease. This review will examine the role of T cells in the pathogenesis of SLE and it will consider pathogenic mechanisms by which T cells escape normal of immunological tolerance. The focus will be on recent studies characterizing autoantigen-reactive human T cells and signaling abnormalities identified in T cells from patients with SLE.     

系统性红斑狼疮患者外周血内皮祖细胞的实验研究

目的探讨系统性红斑狼疮患者外周血内皮祖细胞（EPC）数量、功能是否改变。方法连续选入33例系统性红斑狼疮（SLE）患者做为SLE组,33名门诊健康体检者为对照组。流式细胞分析计量外周血CD34和KDR双阳性细胞,同时原代培养EPC,培养7 d后MTT法检测增殖能力,改良boydon小室法检测迁移能力。结果SLE组外周血EPC数量较对照组显著减少,P〈0.01;SLE组的增殖、迁移能力均较对照组减弱,P〈0.01。结论系统性红斑狼疮患者外周血EPC数量减少,增殖、迁移功能降低,可能是SLE促动脉粥样硬化发生的机制之一。     

钙调神经磷酸酶-活化T细胞核因子与系统性红斑狼疮

系统性红斑狼疮是一种以多种自身抗体产生为特点的侵犯多系统多脏器的自身免疫性疾病,其发病机制尚未明确,目前认为T淋巴细胞异常是SLE的发病的关键.钙调神经磷酸酶-活化T细胞核因子信号通路作为T细胞内重要的生物信号转导通路,在T细胞活化中起到调节枢纽的作用,了解CaN/NFAT信号途径在SLE中的作用及目前相关主要治疗药物的研究现状可为SLE的基础研究及临床治疗提供依据.     

HLA DRB1*1503 allelic haplotype predominance and associated immunodysregulation in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic, relapsing, and remitting disease affecting primarily African American females of child bearing age. Familial aggregation of this disease suggests that at least part of the susceptibility for this disease is genetic, although environmental and hormonal influences are also likely to play a role. Early studies of genetic susceptibility to SLE revealed several of the major histocompatibility complex molecules, namely HLA DR, to be linked to SLE. Meta-analysis of genome scans has yielded loci significant for lupus patients, one of which includes the MHC region.Regulatory T cells are immunoregulatory cells that modulate activated immune cells. These cells play a large role in homeostasis of the immune responses and maintenance of immunologic tolerance, i.e., prevention of autoimmunity. Decreased numbers of regulatory T cells have been described in many autoimmune diseases, including systemic lupus erythematosus.Autoantibody production in systemic lupus erythematosus and the resulting immune complex formation and complex deposition into tissues are arguably the central core of immune dysregulation leading to disease manifestations and symptoms. Inability of the immune system to recognize and inhibit autoreactive immune cells in this particular autoimmune disease may be the result of inappropriate numbers and function of regulatory T cells.This study aims to characterize the immune cell population in patients from our community suffering from systemic lupus erythematosus and to prove that these patients exhibit a unique cellular profile compared to healthy age, race and gender matched control subjects. Surprisingly, our findings demonstrate that patients from the local Mississippi area exhibit increased proportions of CD25⁺ FoxP3⁺ regulatory T cells and CD25⁺ FoxP3⁻ T cells (of CD45⁺ CD3⁺ CD4⁺ helper T cells) as compared to healthy controls.HLA tissue-typing of these lupus patients revealed a prominent subgroup (~ 30%) of patients possessing the HLA DRB1*1503 allele. The investigation of this subgroup demonstrated regulatory T cell composition similar to that of the total lupus group and to that of the non-HLA DRB1*1503 subgroup.Genetic analysis for molecular gene expression levels of various lupus-associated genes by real-time PCR demonstrated a unique profile as compared to healthy controls. Increased gene expression of FoxP3 together with decreased gene expression levels of GATA3, TNFAIP3, and TNFSF4 suggest that variations in gene products compared to healthy controls may be playing a role in the immune cell dysregulation and disproportionate CD25⁺ FoxP3⁺ regulatory T cells.     

雷公藤内酯醇对系统性红斑狼疮患者DC细胞功能及成熟的影响

目的 通过体外实验研究雷公藤内酯醇(triptolide)对系统性红斑狼疮(systemic lupus erythematosus,SLE)患者树突状细胞(dendritic cell,DC)功能及成熟的影响,为进一步阐明雷公藤内酯醇的免疫学活性提供依据.方法 从SLE患者外周血分离单个核细胞,流式细胞仪分选DC,加入0、5、10、30μg/L的雷公藤内酯醇共孵育,24h后收集上清液,ELISA检测IFN-α、IL-6、TNF-α量,5d后收集细胞,流式细胞仪检测DC表型CD11c、CD80、CD86阳性率,光镜观察DC的形态,扫描电镜观察DC的超微结构.结果 雷公藤内酯醇显著减低活动期与非活动期SLE患者IFN-α、IL-6、TNF-α量,并呈雷公藤内酯醇浓度依赖性(P＜0.05);雷公藤内酯醇可抑制SLE患者DC的分化和成熟,并呈雷公藤内酯醇浓度依赖性(P＜0.05).结论 雷公藤内酯醇能够减弱SLE患者DC的功能,并抑制其分化和成熟.     

Abnormalities of B cell subsets in patients with systemic lupus erythematosus

The prototypic autoimmune disease, SLE, is known to be associated with polyclonal B cell hyperreactivity. Developing an understanding of the complex nature of human B cell differentiation, largely through the application of multiparameter flow cytometry to an analysis of circulating B cells has permitted an assessment of whether specific stages of B cell maturation are affected by the tendency for polyclonal B cell activation. Moreover, the analysis of perturbations of the specific stages of B cell maturation has generated new information on whether abnormalities in B cell differentiation are primarily involved in autoimmune disease immunopathology or, rather, are secondary to the inflammatory environment characteristic of subjects with this autoimmune disease. Multivariant analysis has begun to document abnormalities in B cell maturation that are primarily associated with lupus, or, alternatively related to disease duration, disease activity and concomitant medication. Together, these analyses have provided new insights on the role of B cell over-reactivity in SLE.     

红斑狼疮患者外周血内皮祖细胞数量与颈动脉内膜-中膜厚度相关性研究

目的探讨系统性红斑狼疮（SLE）患者外周血内皮祖细胞（EPC）与颈动脉内膜-中膜厚度（IMT）的关系。方法连续选入40例SLE患者做为SLE组,超声检测颈动脉IMT按IMT增厚与否分为IMT正常组和IMT增厚组,20名门诊健康体检者为对照组。流式细胞分析计量外周血EPC（CD34和KDR双阳性细胞）;比较各组EPC数量及直线相关分析EPC数量和IMT相关性。结果SLE组外周血EPC数量较对照组显著减少,P〈0.01;同时在SLE组中IMT增厚组EPC数量低于IMT正常组,P〈0.01,且IMT与外周血EPC数量呈负相关（n=40,r=-0.494,P=0.006）。结论SLE患者存在早期动脉粥样硬化,外周血EPC数量降低与颈动脉IMT增加密切相关,外周血EPC数量降低可能是SLE引起早期动脉粥样硬化的重要原因之一。     

外周血CD19+B细胞PD-L1的表达与系统性红斑狼疮发病的相关性分析

目的:探讨程序性死亡配体1(Programmed death ligand-1,PD-L1)在系统性红斑狼疮(Systemic lupus erythema-tosus,SLE)患者外周血B细胞上的表达及临床意义。方法:应用流式细胞仪检测51例SLE患者和38例健康对照者外周血CD19+B细胞表面PD-L1的表达水平,比较SLE稳定组、活动组和健康对照组以及狼疮肾炎组和无狼疮肾炎组之间CD19+B细胞表面PD-L1表达阳性细胞的百分比,并分析其与临床表现及实验室检查数据的相关性。结果:SLE活动组和稳定组CD19+PD-L1+B细胞百分率均低于健康对照组,活动组又低于稳定组,差异均有统计学意义(均P<0.05)。狼疮肾炎患者CD19+PD-L1+B细胞百分率低于无狼疮肾炎患者(P<0.05)。SLE患者CD19+PD-L1+B细胞百分率与SLEDAI评分、尿蛋白定量、呈负相关,与C3呈正相关。SLE患者中抗dsDNA抗体、抗Sm抗体、抗U1snRNP抗体、抗核小体抗体阳性组外周血B细胞PD-L1表达水平均低于对应阴性组,且均有统计学意义(均P<0.05)。结论:SLE患者外周血CD19+B细胞表达PD-L1下降,与病情活动性和抗体产生有很好的相关性。     

Plasma cells in systemic lupus erythematosus: the long and short of it all

Plasma cells can be classified as long- or short-lived. The lifespan of a plasma cell largely depends on whether it arises from a germinal center or an extrafollicular locus and most importantly whether it can find a survival niche in the spleen or BM. In systemic lupus erythematosus (SLE) patients, long-lived plasma cells are believed to be responsible for the production of anti-RNA and anti-cardiolipin antibodies, whereas short-lived plasma cells, which are more susceptible to anti-proliferation therapies, are the main producers of anti-DNA antibodies. A previous study showed that transient overexpression of interferon-α (IFN-α), a cytokine that plays a pathogenic role in SLE, accelerates disease onset in lupus-prone NZB/W mice. In this issue of the European Journal of Immunology, the same group report that IFN-α induces large numbers of short-lived plasma cells, accompanied by high titers of anti-dsDNA antibodies in NZB/W, but not BALB/c, mice. Our commentary discusses this interesting observation in the context of the previous data regarding plasma cell differentiation and conveys our view about the clinical implications with respect to therapies that target plasma cells in SLE patients.