系统性红斑狼疮患者外周血单个核细胞B细胞刺激因子的异常表达及其临床意义

目的研究系统性红斑狼疮(SLE)患者外周血单个核细胞中B淋巴细胞刺激因子(Blys)的表达情况,并探讨Blys的转录水平与狼疮活动性和狼疮肾炎(LN)的关系,分析Blys在狼疮发病中的作用。方法应用半定量反转录-聚合酶链反应(RT-PCR)法检测活动期组(26例)和缓解期组(22例)SLE患者外周血单个核细胞(PBMCs)BlysmRNA的表达水平,以健康志愿者(20例)作为对照;同时将BlysmRNA的表达水平与患者临床检验指标进行相关分析;采用流式细胞仪技术检测20例SLE患者和16例健康对照膜结合型Blys蛋白水平。结果SLE患者PBMCsB1ysmRNA的表达明显高于正常人(P<0.01),活动期患者的表达高于缓解期(P<0.05);BlysmRNA的表达与狼疮活动指数(SLEDAl)和蛋白尿呈正相关,与补体C3、C4水平呈负相关;抗dsDNA抗体阳性和尿蛋白阳性的SLE患者BlysmRNA的表达高于阴性患者(P<0.05);而且SLE患者PBMCs中Blys的平均荧光强度也显著增加(P<0.05)。结论SLE患者PBMC的膜Blys和BlysmRNA表达均增强,且与狼疮活动性及尿蛋白呈正相关,提示Blys可能参与SLE及狼疮肾炎的发病过程,且有望成为临床观察和疗效评价的新指标。     

系统性红斑狼疮外周血单个核细胞DcR3 mRNA表达研究

目的研究凋亡相关基因诱骗受体3(DcR3)在系统性红斑狼疮患者(SLE)外周血单个核细胞(PBMCs)中的mRNA表达水平。方法应用半定量逆转录-聚合酶链反应(RT-PCR)检测38例SLE患者(21例活动期,17例缓解期)和15例正常人PBMCs中DcR3 mRNA的表达水平,分析其与狼疮活动指数(SLEDAI)的相关性。结果SLE患者PBMCs中,DcR3mRNA表达水平明显高于正常人(P<0.01),但疾病不同病期(活动期与缓解期)其表达水平无统计学差异(P>0.05);DcR3 mRNA表达与SLEDAI不相关(r=-0.024,P>0.05)。结论SLE患者PBMCs DcR3 mRNA表达增加,提示DcR3可能与SLE免疫细胞凋亡异常和免疫调节的紊乱有关,参与了SLE的发病过程。     

系统性红斑狼疮患者外周血单个核细胞端粒保护蛋白TPP1及POT1基因表达的研究

目的 研究端粒保护蛋白TPP1及POT1基因在系统性红斑狼疮(SEE)患者与健康人外周血单个核细胞(PBMCs)的表达及其与SEE肾损、疾病活动度的相关性.方法 应用实时荧光定量聚合酶链反应检测SEE患者活动组28例、缓解组20例及健康对照组30例PBMCs TPP1、POT1 mRNA表达水平,并且与SEE患者临床指标进行相关性分析.结果 SLE组与健康对照组相比,TPP1及POT1基因表达明显降低(P均<0.01),活动组与缓解组均显著低于健康对照组(P均<0.05);POT1基因在活动组的表达显著低于缓解组(P<0.05);TPP1及POT1基因在肾损组的表达低于无肾损组(P<0.01),在SLE肾损患者中,尿蛋白定量与TPP1及POT1基因的表达水平呈负相关(P<0.05),尿白细胞与POT1基因呈负相关(P<0.05);红细胞沉降率、C反应蛋白、抗核抗体与TPP1、POT1基因的表达及SLE疾病活动指数(SLEDAI)评分没有相关性;POT1 mRNA的表达与血清IsG、SLEDAI评分呈负相关(P<0.05,P<0.01),与补体C3呈正相关(P<0.01);TPP1 mRNA的表达与血清IgG、SLEDAI评分及C3没有相关性.结论 端粒保护蛋白TPP1和POT1基因在SLE的发病中发挥重要作用,其参与了SLE肾脏损害的病理过程,POT1可作为SEE疾病活动的有效的评判指标.     

系统性红斑狼疮外周血B淋巴细胞激活及TOLL样受体9表达

目的探讨系统性红斑狼疮(SLE)外周血单个核细胞(PBMCs)中B淋巴细胞的激活状态及TOLL样受体9(TLR9)表达水平。方法用流式细胞术测定25例SLE患者PBMC中CD19 B细胞及CD19 CD38 B细胞的比例。用反转录-聚合酶链反应(RT-PCR)半定量方法检测38例SLE患者PBMCs中TLR9mRNA的表达水平。分析TLR9mRNA的表达水平与SLE活动性指数(SLEDAI)的相关性。结果SLE患者PBMCs中CD19 B细胞和CD19 CD38 B细胞的百分数均高于正常对照组(P<0.01)。活动期SLE患者PBMCs的TLR9mRNA表达低于缓解组(P<0.01)及正常对照(P<0.01),缓解期和正常对照组相比,差异无统计学意义(P>0.05)。TLR9mRNA的表达与SLEDAI评分呈负相关。结论SLE患者PBMC中激活B细胞增多。活动期SLE患者PBMC的TLR9的表达水平降低,与SLEDAI呈负相关。TLR9可能参与SLE的病理发病过程。     

系统性红斑狼疮患者程序性死亡配体-1表达的初步研究

目的检测系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)程序性死亡配体-1(PD-L1)的表达水平,探讨其在系统性红斑狼疮发病过程中的作用。方法密度梯度离心法分离系统性红斑狼疮患者和正常人PBMC,采用半定量RT-PCR检测PBMC的PD-L1mRNA表达。结果系统性红斑狼疮患者活动期组和稳定期组的PD-L1mRNA表达与对照组比较明显增高,差异有显著性(P均<0.05);但PD-L1mRNA表达在系统性红斑狼疮活动期组与稳定期组之间比较无显著性差异(P>0.05)。结论系统性红斑狼疮患者外周血单个核细胞PD-L1mRNA表达水平增加,程序性死亡配体-1可能在系统性红斑狼疮的发病机制中有一定的作用。     

Elevated Th17 cells are accompanied by FoxP3+ Treg cells decrease in patients with lupus nephritis

To investigate the variations of T-helper 17 (Th17) and regulatory T (Treg) cells in patients with lupus nephritis (LN), a total of 60 systemic lupus erythematosus patients and 28 healthy controls (HCs) were enrolled. The frequency of Th17 cells and Treg cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometric analysis. The serum concentrations of interleukin-17 (IL-17) and transforming growth factor-beta 1 (TGF-β1) were measured by enzyme-linked immunosorbent assay (ELISA). The results demonstrated in LN patients a significant decrease in the frequency of CD4+CD25^high and CD4+CD25+FoxP3+ T cells and a significant increase in the frequency of Th17 cells in peripheral blood, and the ratio of Th17 to Treg cell frequency was significantly increased along with increased SLEDAI scores. LN patients had a lower percentage and expression of FoxP3 in CD4+CD25^high T cells than SLE patients without nephritis. The concentration of TGF-β1 was found decreased in SLE patients compared with that from healthy controls, though no significant difference was found between LN patients and SLE patients without nephritis. The expression of IL-17 levels in LN patients exhibited a significant increase compared with patients without nephritis and healthy controls. Based on our results, the significantly elevated Th17 cells are accompanied by FoxP3+ Treg cells decrease in lupus nephritis, suggesting that Th17/Treg functional imbalance may be involved in the pathogenesis of renal damage in SLE patients.     

系统性红斑狼疮患者外周血单个核细胞增殖诱导配体及其受体的表达

目的 探讨系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)中增殖诱导配体(APRIL)及其受体B细胞成熟抗原(BCMA)、跨膜激活剂及钙调亲环素配体相互作用分子(TACI)mRNA的表达和意义.方法 应用实时定量聚合酶链反应(real-time PCR)技术,检测66例SLE患者及25名正常人PBMC中APRIL及其受体mRNA的表达,采用2-AACT对目标基因的表达量进行评估.结果 SLE活动组和缓解组的APRIL mRNA、BCMA mRNA和TACI mRNA的表达水平均明显高于正常对照组(均P<0.01);且SLE活动组的APRIL mRNA和TACI mRNA的表达水平显著高于SLE缓解组(分别P<0.01,P<0.05),BCMA mRNA的表达在SLE活动组与缓解组之间比较差异无统计学意义;此外,APRILmRNA和TACI mRNA在SLE肾损组的表达显著高于非肾损组(均P<0.01).结论 SLE患者PBMC中APRIL及其受体的表达水平增高,可能在SLE发病机制中发挥重要作用.     

系统性红斑狼疮患者外周血单个核细胞c-kit受体表达的研究

目的：探讨系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMC）中c-kit受体的表达及其临床意义。方法：采用免疫荧光标记，流式细胞仪检测SLE患者PBMC的c-kit受体蛋白（CD117）表达，反转录－聚合酶链式反应（RT－PCR）检测其c-kit mRNA的表达水平，并分别与正常人比较。结果：SLE患者PBMC中c-kit受体及其mRNA表达水平与正常组相比显著增高（P＜0．05）；活动期与非活动期相比显著增高（P＜0．05），非活动期SLE患者PBMC的c-kit受体蛋白表达与正常人差异无显著性（P＞0．05），PBMC的c-kit受体蛋白表达与其SLEDAI显著相关（P＜0．01），结论：SLE患者PBMC c-kit受体蛋白水平及其mRNA表达水平均显著高于正常人，且与疾病活动呈正相关，c-kit受体可能在SLE的病程变化中起着重要作用。     

转化生长因子βⅡ型受体在狼疮肾炎患者外周血单个核细胞表达的意义

目的 探讨狼疮肾炎(LN)患者外周血单个核细胞(PBMCs)转化生长因子βⅡ型受体(TβR Ⅱ) mRNA表达水平及其与疾病活动性的关系.方法 应用反转录-聚合酶链反应(RT-PCR)法检测44=例LN患者(均为活动期患者)、21例其他非LN患者和40名健康对照组PBMCs中TβRⅡ mRNA的表达水平,LN患者中未使用与使用激素和(或)免疫抑制剂患者分别为16例和28例.结果 LN患者PBMC中T13R H mRNA水平1.7±1.0显著低于非LN组4.0±3.1及健康对照组4.1±2.5(P<0.01);LN患者中未使用激素和(或)免疫抑制剂组T13R H mRNA的表达水平1.3±1.0低于用药组2.0+0.9(P<0.05);LN患者PBMCs中的T13RII mRNA表达水平与系统性红斑狼疮疾病活动指数(SLEDAI)评分标准(r-0.309,P<0.05)及抗双链DNA抗体(r-0.401,P<0.01)呈显著负相关,与补体C3呈显著正相关(r=0.621,P<0.01).结论 LN患者PBMCs中的TβRⅡmRNA表达水平降低,TβRⅡ参与了LN的发病过程,并与疾病的活动性显著相关;应用激素和(或)免疫抑制剂可以提高TTβRⅡ mRNA的表达,减轻炎症损害.     

神经颗粒素在系统性红斑狼疮患者外周血单个核细胞中的表达

目的 探讨神经颗粒素在系统性红斑狼疮(SLE)患者和正常人外周血单个核细胞(PBMCs)的表达状态.方法 对比分析SLE PBMCs基因表达系列分析(SAGE)文库的高表达标签,并采用反转录聚合酶链反应(RT-PCR)法检测与正常人群有明显差异表达的神经颗粒素在SLE患者PBMCs的mRNA表达水平.结果 对比分析SLE PBMCs和正常人各类淋巴细胞SAGE文库显示:神经颗粒素标签仅异位高表达于SLE患者,而几乎不表达于正常人各类淋巴细胞.RT-PCR检测证实:活动组SLE患者神经颗粒素mRNA表达水平较正常对照明显增加(P＜O.001),而缓解组SLE患者其表达水平仅稍有增加(P＞O.05).结论 神经颗粒素作为一种前凋亡因子,高表达于SLE PBMCs,可能介导或参与SLE异常的免疫调节反应.     

Expression of inducible co-stimulator on peripheral blood T lymphocytes in patients with lupus nephritis

Systemic lupus erythematosus (SLE) is a complex autoimmune disease and lupus nephritis (LN) represents a major clinical manifestation. Studies have shown that elevated inducible co-stimulator (ICOS) in SLE. The purpose of the study was to investigate the expression of ICOS on T cells in patients with LN. Flow cytometry (FCM) was used to analyze the expression of ICOS on peripheral blood T lymphocytes in LN patients, SLE patients without nephritis, and healthy controls. The expression of ICOS on CD4 + CD45RO + and CD8 + CD4RO + T cells was significantly increased in SLE patients when compared with healthy controls (P < 0.001). In addition, ICOS expression in patients with nephritis was higher than those without nephritis (P < 0.01). Taken together, our results suggest that ICOS co-stimulatory pathway is important in the pathogenesis of LN; blockade of the pathway might represent a novel therapeutic strategy for the treatment of LN.     

Dysfunction of TRIM21 in interferon signature of systemic lupus erythematosus

Abstract

Objectives: TRIM21 is an E3 ubiquitin ligase for interferon regulatory factors (IRFs) that are involved in innate and acquired immunity. Here, we evaluated the role of TRIM21 in the interferon (IFN) signature of systemic lupus erythematosus (SLE).

Methods: Twenty SLE patients and 24 healthy controls were enrolled in this study. We analyzed mRNA expression of TRIM21, type I IFN, and IFN-inducible genes in peripheral blood mononuclear cell (PBMC). The protein levels of IRFs were assessed by Western blotting in PBMCs cultured with or without MG-132.

Results: The expression of TRIM21 mRNA and protein was significantly higher in SLE PBMCs as compared to healthy controls. There was a correlation between TRIM21 mRNA expression and SLE activities. In contrast to a negative correlation between mRNA expression level of TRIM21 and those of type I IFNs in healthy controls, we found a positive correlation between them in anti-TRIM21 antibody-positive SLE patients. Neither positive nor negative correlation was observed in the autoantibody-negative SLE patients. Western-blotting analysis revealed impaired ubiquitin-dependent proteasomal degradation of IRFs in SLE PBMCs.

Conclusion: Our study showed ubiquitin-dependent proteasomal degradation of IRFs was impaired in anti-TRIM21 antibody-dependent and -independent fashions, leading to amplification of IFN signature in SLE.     

系统性红斑狼疮患者外周血单个核细胞组蛋白H3赖氨酸4三甲基化水平的研究

目的 研究系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)组蛋白H3赖氨酸4(H3K4)三甲基化(Me3)水平.方法 梯度密度离心法分离10例SLE活动期患者、7例SLE稳定期患者和8名健康者的PBMCs,采用染色质免疫共沉淀联合芯片技术(CHIP-chip)在全基因组范围内对SLE患者及健康者的PBMCs组蛋白H3K4me3进行高通量的筛选.染色质免疫共沉淀一实时定量聚合酶链反应(ChlP-qPCR)验证芯片结果.定量反转录一聚合酶链反应(qRT-PCR)检测H3K4me3显著差异基因的mRNA表达水平.结果 10例SLE活动期患者与健康对照相比较,鉴定出413个基因存在H3K4me3显著差异,其中137个基因显示H3K4me3程度增高,276个基因H3K4me3程度降低;7例SLE稳定期患者与健康对照相比较,发现393个基因存在H3K4me3表达差异,其中有112个基因H3K4me3程度增高,281个基因H3K4me3程度降低.ChIP-qPCR验证结果与CpG岛芯片的结果相一致.结论 SLE患者与健康者之间的PBMCs存在组蛋白H3K4me3显著改变.ChIP-chip技术有利于进一步揭示SLE分子机制,发现新的治疗靶点.     

系统性红斑狼疮与CD19基因多态性的相关性研究

目的研究CD19基因第4外显子705位点(以下简称CD19基因705位点)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)和狼疮肾炎(LN)的相关性。方法103例患者诊断均符合1982年美国风湿病学会修订的SLE分类标准,男13例,女90例,其中62例伴有LN。正常对照组110例,男21例,女89例。全部研究对象均为无血缘关系的中国南方地区汉族人群。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对所有SLE患者和正常对照者进行CD19基因705位点多态性检测。结果CD19基因705位点多态性在中国南方地区汉族人群中普遍存在。SLE患者CD19基因705位点基因型和等位基因频率分布与正常对照组比较差异无统计学意义(P>0.05);CD19基因705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组比较及LN患者和正常对照组比较以及伴有LN患者与未伴有LN的SLE患者间比较,差异均无统计学意义(P>0.05)。结论CD19基因705位点多态性与SLE及LN无相关性。     

系统性红斑狼疮患者外周血T淋巴细胞Foxp3的表达和转化生长因子-β1水平与病情的相关性

目的 探讨系统性红斑狼疮(SLE)患者外周血调节性T淋巴细胞Foxp3 mRNA和转化生长因子(TGF)-β1的水平与SLE病情活动的关系.方法 对SLE患者采用实时定量聚合酶链反应(PCR)检测外周血单个核细胞Foxp3 mRNA的表达.对病情活动组患者进行随访,在疾病稳定期再次检测Foxp3 mRNA水平并用酶联免疫吸附试验(ELISA)检测疾病缓解前后血浆TGF-β1的浓度.结果 病情活动组Foxp3 mRNA水平明显低于非活动组(P<0.01)和健康对照组(P<0.01).在疾病稳定期Foxp3 mRNA水平和血浆TGF-β1浓度较活动期明显升高.结论 Foxp3表达及TGF-β1浓度与SLE疾病活动呈负相关,提示调节性T淋巴细胞在SLE发病中有重要作用.     

SLE患者血清MMP-9、TIMP-1水平测定及其临床意义

目的探讨系统性红斑狼疮（SLE）患者血清基质金属蛋白酶9（MMP-9）及其抑制物（TIMP-1）的表达特点及临床意义。方法用双抗体夹心酶联免疫吸附试验（ELISA）检测64例SLE患者（SLE组）和25名健康人（对照组）血清MMP-9和TIMP-1的水平并进行比较分析。结果 SLE组患者血清MMP-9水平明显低于对照组,TIMP-1明显高于对照组（P〈0.01）,且MMP-9/TIMP-1低于对照组（P〈0.05）;SLE患者活动期血清MMP-9、MMP-9/TIMP-1明显低于缓解期（P〈0.05）,但TIMP-1的水平差异无统计学意义（P〉0.05）;狼疮肾炎组MMP-9低于非肾炎组（P〈0.05）,但TIMP-1差异无统计学意义（P〉0.05）;MMP-9及TIMP-1水平在LN各病理类型患者中的差异无统计学意义（P〉0.05）;患者的临床表现与MMP-9及TIMP-1水平无明显关系。结论 MMP-9及TIMP-1可能参与SLE的发病,血清MMP-9水平可作为反映SLE活动程度、肾脏损害的指标。     

活动性系统性红斑狼疮自噬及相关基因研究

目的 观察活动性系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)的自噬现象并检测相关基因的表达水平. 方法 以初诊及新发作的活动性SLE患者20例为病例组,类风湿关节炎(RA)患者10例和健康志愿者10名分别作为对照组.密度梯度离心法分离PBMC,并利用贴壁法除去单核细胞.运用透射电镜(TEM)观察细胞的超微结构,半定量反转录-聚合酶链反应(RT-PCR)及实时定量RT-PCR检测各组PBMC中Beclin1、微管相关蛋白1轻链3(MAPLC3)mRNA的表达水平. 结果 TEM发现活动性SLE患者PBMC中存在自噬现象;Beclinl和MAPLC3 mRNA在活动性SLE患者表达量均增高,且分别较RA组和健康对照组表达差异有统计学意义. 结论 活动性SLE患者外周血PBMC存在自噬现象,且细胞自噬相关基因表达较健康对照组和RA组增强,这可能与SLE的发生、发展相关.     

淋巴细胞趋化因子受体mRNA在系统性红斑狼疮患者外周血单个核细胞的表达

目的探讨淋巴细胞趋化因子受体(XCR1)mRNA在系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)中的表达,及其与疾病的相关性。方法收集93例确诊的SLE患者和30名健康对照组,收集PBMC,提取RNA。应用反转录-聚合酶链反应(RT-PCR)方法检测研究对象XCR1mRNA表达水平。结果!"XCR1mRNA在PBMC中表达水平,患者组(1.57±0.84)与正常对照组(0.19±0.14),两者差异无统计学意义(P>0.05)。活动期(2.09±1.38)与对照组比较,两者差异有统计学意义(t=2.392,P=0.02);活动期与非活动期(0.31±0.24)比较,差异有统计学意义(t=3.091,P=0.003);非活动期与对照组比较,差异无统计学意义(P>0.05)。"#SLE患者组XCR1mRNA水平与疾病活动度评分(SLEDAI)关系:SLE患者组PBMC中XCR1mRNA表达水平与SLEDAI作直线相关性分析,XCR1mRNA水平与SLEDAI(r=0.540,t=5.445,P=0.000)呈正相关。"$SLE患者PBMC中XCR1mRNA表达与临床表现及实验室检查相关性:SLE抗SSA抗体阳性患者(17/68,1.4±1.2)比阴性患者(51/68,3.5±4.9),其XCR1mRNA表达水平降低,差异有统计学意义(t=2.78,P=0.007)。结论XCR1mRNA表达水平在PBMC中活动期SLE患者比非活动期及对照组增高,与疾病的活动性(SLEDAI)正相关,非活动期与对照组差异无统计学意义。SLE抗SSA抗体阳性患者比阴性患者,其XCR1mRNA表达水平降低,两组均较健康对照组增高。提示XCR1参与疾病的发展,与疾病的活动性相关,XCR1可能参与抗SSA抗体的形成过程,造成组织损伤。     

Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus

OBJECTIVE: To study the contribution of interferon-alpha (IFNalpha) and IFNgamma to the IFN gene expression signature that has been observed in microarray screens of peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE). METHODS: Quantitative real-time polymerase chain reaction analysis of healthy control PBMCs was used to determine the relative induction of a panel of IFN-inducible genes (IFIGs) by IFNalpha and IFNgamma. PBMCs from 77 SLE patients were compared with those from 22 disease controls and 28 healthy donors for expression of IFIGs. RESULTS: Expression of IFNalpha-inducible genes was significantly higher in SLE PBMCs than in those from disease controls or healthy donors. The level of expression of all IFIGs in PBMCs from SLE patients with IFNalpha pathway activation correlated highly with the inherent responsiveness of those genes to IFNalpha, suggesting coordinate activation of that cytokine pathway. Expression of genes preferentially induced by IFNgamma was not significantly increased in SLE PBMCs compared with control PBMCs. IFNalpha-regulated gene-inducing activity was detected in some SLE plasma samples. CONCLUSION: The coordinate activation of IFNalpha-induced genes is a characteristic of PBMCs from many SLE patients, supporting the hypothesis that IFNalpha is the predominant stimulus for IFIG expression in lupus.     

Emerging role of TWEAK-Fn14 axis in lupus,a disease related to autoimmunity and fibrosis

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder. Lupus nephritis (LN) is one of the severe clinical implications in SLE, and this was relates to fibrosis in the kidney. As an important marker in the tumor necrosis factor (TNF) superfamily, TNF-like weak inducer of apoptosis (TWEAK) has been given much attention with respect to its role in regulating pro-inflammatory immune response. Fibroblast growth factor-inducible 14 (Fn14), the sole receptor for TWEAK, has been found expressed in different immune and non-immune cells. TWEAK binds to Fn14, and then regulates inflammatory components production via downstream signaling pathways. To date, dysregulated expression of TWEAK, Fn14 has been reported in SLE, LN patients, and in vivo, in vitro studies have discussed the significant role of TWEAK-Fn14 axis in SLE, LN pathogenesis, partly through mediating the fibrosis process. In this review, we will discuss the association of TWEAK-Fn14 axis in lupus. Understanding the relationship will better realize the potential for making TWEAK-Fn14 as a marker for the diseases, and will help to give many clues for targeting them in treatment of lupus in the future.