系统性红斑狼疮病人环孢素A受体mRNA的表达

目的 探讨静止期、活动期系统性红斑狼疮病人（SLE）外周血单个核细胞（PBMC）环孢素A受体（CyP）mRNA表达及糖皮质激素对其表达的影响,为临床应用环孢素A辅助治疗该病提供理论依据。方法 采用逆转录PCR方法,经凝胶图像半定量分析,检测患者外周血单个核细胞CyP mRNA的表达。结果 SLE病人外周血单个核细胞存在有CyPmRNA的表达,静止期较正常人差异无显著性（P＞0．05）意义,但在活动期CyPmRNA的表达较正常人和静止期病人明显降低（P＜0．01）,地塞米松处理后,活动期病人CyPmRNA的表达水平显著上升（P＜0．01）。结论 SLE病人有CyPmRNA的表达,但活动期明显下降,糖皮质激素可改善CyP mRNA的表达。     

白介素17A受体在系统性红斑狼疮患者外周血B淋巴细胞的表达及意义

目的:研究白介素17A受体(IL-17AR)在系统性红斑狼疮(SLE)患者外周血B淋巴细胞内的表达情况及其临床意义。方法:流式细胞术检测60例SLE患者及33例健康人外周血B细胞上IL-17AR的表达水平。并将其与有关临床及实验室指标进行相关性分析。结果:SLE患者组的IL-17AR+细胞表达比例为(47.58±17.20)%,高于正常对照组(40.71±11.82)%(P<0.05)。在SLE患者中:口腔溃疡组、有浆膜炎组、有肾脏病变组、有免疫异常组分别高于相应的无症状组(P<0.05)。在抗Sm-D1抗体阳性组及抗核小体抗体阳性组分别高于相应的抗体阴性组(P<0.05)。IL-17AR+细胞比例与SLE疾病活动指数(SLEDAI)、C反应蛋白(CRP)、甘油三酯呈正相关;与间接胆红素、血清白蛋白的表达负相关(P<0.05)。B淋巴细胞比例与血清IgG、ALT、直接胆红素的表达呈正相关;与胆固醇、甘油三酯、低密度脂蛋白的表达呈负相关(P<0.05)。结论:IL-17AR在SLE患者B细胞上表达上调,且与病情有一定的相关性。提示IL-17/IL-17AR可能在SLE发病中起着重要作用。     

系统性红斑狼疮患者性激素及性激素受体的改变及意义

应用放射配体结合法检测３０例系统性红斑狼疮患者（ＳＬＥ）外周血淋巴细胞雌激素受体（ＥＲ）和雄激素受体（ＡＲ），同时应用放射免疫分析检测血浆雌二醇（Ｅ２）及睾酮（Ｔ）水平。结果表明：１．ＳＬＥ患者血浆Ｅ２略高于对照组，但无统计学意义，血浆Ｔ无明显改变；２．ＳＬＥ患者淋巴细胞ＥＲ明显高于对照组（Ｐ〈０．０１），ＡＲ明显低于对照组（Ｐ〈０．０５）；３．伴狼疮肾炎的２０例ＳＬＥ，ＥＲ明显高于不伴肾炎的１０     

系统性红斑狼疮病人外周血白细胞TNFRSFl2mRNA表达的研究

目的：了解肿瘤坏死因子受体超家族成员12(TNFRSFl2)mRNA在系统性红斑狼疮(SLE)外周血白细胞中的表达是否异常，初步判断TNFRSFl2是否为SLE的易感基因。方法：采用TaqMan one-step RT-PCR方法。分别对SLE病人、正常人和类风湿性关节炎(RA)病人外周血白细胞TNFRSFl2 mRNA的表达进行检测。结果：SLE病人TNFRSFl2 mRNA的表达形式与表达量和正常人相比均存在差异，SLE病人白细胞存在TNFRSFl2 mRNA的两类形式剪切体。分别为编码膜结合蛋白形式和分泌形式的TNFRSF12，而正常人只有后者，在PHA刺激后才开始同时表达前者。并且TNFRSFl2 mRNA在SLE病人中的表达量与病情活动度和肾脏累及相关。结论：提示TNFRSFl2在SLE的发病机制中起一定作用,因此可能是SLE的易感基因。     

Toll样受体与系统性红斑狼疮和动脉粥样硬化

目前,越来越多的研究表明Toll样受体信号通路在系统性红斑狼疮(SLE)和动脉粥样硬化(AS)等疾病的发病中发挥着重要作用。同时,SLE患者早发动脉粥样硬化发病率显著增高,提示两者的发病存在相关性。SLE多见于年轻女性,其发生心血管事件的概率高达同年龄组正常人群的50倍。     

雌激素受体与系统性红斑狼疮的关系

系统性红斑狼疮（SLE）发病机理涉及免疫系统自身识别的丧失,较易发生于生育期女性。雌激素对SLE的发病及病情发展有重要影响。雌激素通过与T、B细胞核内表达的雌激素受体ER-α和ER-β结合进而刺激或调节特异性免疫相关基因的转录。受体结构以及与靶基因相互作用的差异造成了雌激素的异常活动,使得对自身抗原耐受起重要作用的一系列调节通路紊乱,从而导致自身免疫病如SLE的发生。多种经典和非经典雌激素信号的传导通路在转录和转录后水平均调控T细胞活化基因的表达,造成SLE患者的T细胞对雌激素应答的敏感性差异。     

免疫球蛋白受体3A基因-72R/S单核苷酸多态性与系统性红斑狼疮的遗传易感性

目的探讨位于人类1号染色体长臂2区3带(1q23-24)免疫球蛋白受体3A(Fc gamma recep-tor3A,FCGR3A)基因-72R/S单核苷酸多态性与系统性红斑狼疮(systemic lupus erythematosus,SLE)的遗传易感性关联情况。方法采用聚合酶链反应和限制性酶切片段长度多态性方法检测人类1q23FCGR3A基因多态性,采用家系内关联性分析(family-based association test,FBAT),对119个中国汉族SLE患者家系(核心家系95个)119例SLE患者和316个家系成员中FCGR3A-72R/S多态性位点进行等位基因和基因型别分析,SLE的诊断采用1997年美国风湿学修定的标准。结果在119例SLE患者中,R、S等位基因频率分别是39.4%和60.6%;基因型RR、RS和SS的频率分别是9.1%、60.6%、30.3%。FBAT软件分析结果显示-72R/S(rs403016)与SLE显著相关;在附加模型(Z=2.544,P=0.01097)、隐性模型(Z=2.198,P=0.02795)均显示-72R等位基因与SLE遗传易感性有关。传递不平衡检验显示其中R等位基因优势传递给患病子女(χ2=9.30,P=0.0032)。结论在中国汉族SLE家系中发现FCGR3A-72R/S多态性与SLE存在关联或者与疾病基因座存在连锁;说明携带-72R等位基因可能与提高SLE遗传易感性有关。     

系统性红斑狼疮病人外周血白细胞TNFRSF12mRNA表达的研究

目的 :了解肿瘤坏死因子受体超家族成员 12 (TNFRSF12 )mRNA在系统性红斑狼疮 (SLE)外周血白细胞中的表达是否异常 ,初步判断TNFRSF12是否为SLE的易感基因。方法 :采用TaqManone stepRT PCR方法 ,分别对SLE病人、正常人和类风湿性关节炎 (RA)病人外周血白细胞TNFRSF12mRNA的表达进行检测。结果 :SLE病人TNFRSF12mRNA的表达形式与表达量和正常人相比均存在差异 ,SLE病人白细胞存在TNFRSF12mRNA的两类形式剪切体 ,分别为编码膜结合蛋白形式和分泌形式的TNFRSF12 ,而正常人只有后者 ,在PHA刺激后才开始同时表达前者。并且TNFRSF12mRNA在SLE病人中的表达量与病情活动度和肾脏累及相关。结论 :提示TNFRSF12在SLE的发病机制中起一定作用 ,因此可能是SLE的易感基因。     

系统性红斑狼疮中A20表达特点的研究

目的:了解系统性红斑狼疮(SLE)患者外周血中肿瘤坏死因子α诱导蛋白3(TNFAIP3,也称A20)、核因子κB(NF-κB)、黏膜相关淋巴瘤易位基因1(MALT1)及其转录本1(MALT1V1)的mRNA表达特点。方法:采用real-time PCR法检测21例SLE患者(其中合并硬皮症2例,合并类风湿关节炎1例,合并淋巴瘤1例)及31例健康人外周血单个核细胞(PBMC)中MALT1、A20、NF-κB和MALT1V1 mRNA的表达情况。结果:SLE样本中,A20 mRNA表达水平较健康人明显降低(P0.01),MALT1和NF-κB也较健康人降低(P0.01)。在健康人组,A20和NF-κB mRNA的表达水平未呈现明显相关性,MALT1和NF-κB则呈正相关(P0.05);而在SLE组中,A20和NF-κB mRNA则显示出显著正相关(P0.05),MALT1和NF-κB则不存在相关性。SLE中MALT1V1表达量显著低于正常人(P0.05),相关性研究还显示,健康人中A20和MALT1V1存在正相关关系(P0.01),在SLE中则不存在(P0.05)。结论:本研究首先提供了MALT1-A20-NF-κB通路在SLE中的表达特点。SLE患者异常低表达A20,这可能与患者低免疫耐受相关,其与NF-κB表达的正相关性情况可能与其它因素的调控有关,有待进一步证实。     

系统性红斑狼疮外周血单个核细胞cFLIP-L mRNA和cFLIP-S mRNA表达的研究

目的 探讨系统性红斑狼疮(system lupus erythematosus,SLE)患者外周血单个核细胞(peripheral blood monouuclear cells,PBMC)中细胞型Fas相关死亡域样白介素-1β转换酶抑制蛋白(cFLIP)表达的意义.方法 应用半定量RT-PCR方法检测38例SLE患者和21名正常人PBMC中cFLIP-L mRNA和cFLIP-S mRNA的表达水平,并与SLE疾病活动指数(SLEDAI)评分进行相关性分析.结果 ① SLE患者PBMC中cFLIP-L mRNA和cFLIP-S mRNA表达水平均明显高于正常对照组(P＜0.01);SLE患者活动组cFLIP-L mRNA表达水平显著高于非活动组(P＜0.05),cFLIP-S mRNA表达水平在SLE患者活动组与非活动组之间没有显著性差异(P＞0.05). ② SLE患者cFLIP-L mRNA表达水平与SLEDAI评分呈正相关(r=0.423,P＜0.01);而cFLIP-S mRNA表达水平与SLEDAI评分无明显相关性(r=0.270,P＞0.05).结论 cFLIP-L mRNA和cFLIP-S mRNA可能在SLE发病机制中起重要作用.     

Functional Property of la-Positive T Cells in Peripheral Blood from Patients with Systemic Lupus Erythematosus

Ia-positive (Ia+) T cells in peripheral blood and their functional property were examined in patients with systemic lupus erythematosus (SLE). Binding of specific monoclonal antibodies was assessed by indirect immunofluorescence. Functional study of Ia+ T cells was carried out in coculture experiments by measuring the IgG secreted into the culture supernatant. We found that the percentage of Ia+ T cells in peripheral blood from patients with SLE was raised and the rise correlated positively with serum gamma globulin and IgG level. The elevation was further increased after stimulation with DNA in vitro, indicating the presence of DNA-sensitive T cells. Functionally, Ia+ T cells acted as helper cells in spontaneous IgG synthesis of SLE B cells, and were enriched in the OKT4 subset. These results indicate that SLE T cells are activated in vivo and that the Ia+ T cells may play a crucial role in the immunoregulatory function. Accordingly, demonstration of Ia antigens on T cells by monoclonal antibody may provide a useful tool for the measurement of immunological activity in patients with SLE.     

Expression of CTLA-4 Molecule in Peripheral Blood T Lymphocytes from Patients with Systemic Lupus Erythematosus

CTLA-4 is a cell surface molecule expressed on activated T cells that is suggested to deliver a negative signal for T cell activation. Since CTLA-4 might be a negative regulator of autoimmune diseases, we investigated its expression on T cells from 20 patients with systemic lupus erythematosus (SLE) by flow cytometric analysis and RT-PCR. We found that although CTLA-4 mRNA was readily detected in all patients and controls, only a very minor subset of T cells expressed detectable surface CTLA-4 molecules in both groups. But patients with SLE had significantly increased percentages of CTLA-4-positive T cells compared with normal controls, implying at least that there was no apparent defective expression of CTLA-4 molecule in human lupus. The kinetics of CTLA-4 expression on T cells stimulated in vitro with PMA plus ionomycin were similar in normal controls and patients with SLE. The expression of CTLA-4 molecules after stimulation increased gradually and peaked at 72 hr. However, the induction of CTLA-4 expression on patients' T cells appeared to be weaker than that of normal individuals. Whether this reflects impaired down regulation by CTLA-4 molecules in SLE patients needs to be clarified further.     

Expression and Functional Role of HLA-G in Immune Cells from Patients with Systemic Lupus Erythematosus

Human leukocyte antigen (HLA)-G is a class I non-classical HLA molecule with an important regulatory role on the immune response. The possible role of this molecule in the pathogenesis of SLE has not been explored. In this work, we evaluated the expression and function of HLA-G in SLE patients. We studied 37 SLE patients as well as 25 healthy donors. Peripheral blood monocytes and in vitro-generated dendritic cells (DCs) were analyzed for HLA-G expression by flow cytometry. We found that monocytes from SLE patients as well as mature CD83+ DCs showed a diminished expression of HLA-G compared with healthy controls. In addition, monocytes from SLE patients showed a diminished induction of HLA-G expression in response to stimulation with IL-10. Furthermore, functional assays showed that these monocytes pre-treated with IFN-γ exhibited a diminished capability to inhibit the proliferation of autologous lymphocytes. Finally, lymphocytes from SLE patients tended to display a lower acquisition of HLA-G (by trogocytosis) from autologous monocytes compared to controls. Our results might have implications for the immune abnormalities observed in patients with SLE.     

HLA-DP-Positive T Cells in Patients with Systemic Lupus Erythematosus

HLA-DP⁺ T cells in peripheral blood from 23 patients with systemic lupus erythematosus (SLE) were examined using two-colour flow cytometry analysis. A marked increase of HLA-DP⁺ T cells was observed in patients with SLE (20.5–98.7%; 59.8 ± 20.8%) in comparison to normal subjects (1.3–20.6%; 11.1 ± 7.2%), and the ratio of these cells greatly exceeded that of the HLA-DR+ T cells (6.5–49.1%; 21.5 ± 12.7%). This high frequency of HLA-DP+ T cells in patients with active SLE decreased with predonisolone therapy. When the lymphocytes from normal subjects were stimulated with PHA in vitro, HLA-DP⁺ T cells increased from 1.8 to 59.2%. Therefore, it appears that the HLA-DP antigen expression on T cells is a practical marker for monitoring changes in the proportion of activated T cells in patients with SLE during the course of therapy.     

CD40在系统性红斑狼疮外周血淋巴细胞的表达

使用密度离心法分离SLE患者和正常人外周血单个核细胞 (PBMC ) ,采用流式细胞术检测B淋巴细胞白细胞分化抗原 4 0 (CD4 0 )的表达水平 ,进行SLE患者 (活动期和缓解期 )和正常人之间的比较 ;并进行B淋巴细胞CD4 0表达水平和血清抗dsDNA抗体水平及狼疮活动指数 (SLEDAI)的相关分析。结果表明 ,活动期SLE患者外周血B淋巴细胞比例 (% )和其表达CD4 0的比例 (% )均明显高于缓解期SLE患者和对照组 ,其表达CD4 0的平均荧光强度 (MFI)在活动期SLE患者最高 ,缓解期SLE患者稍低 ,对照组最低 ;相关分析结果表明 ,活动期SLE患者B淋巴细胞CD4 0的表达比例 (% )和强度 (MFI)均与血清抗dsDNA抗体及SLEDAI呈正相关 ,后两者呈高度相关 ;缓解期SLE患者B淋巴细胞表达CD4 0的强度 (MFI)和SLEDAI呈正相关。CD4 0在活动期SLE患者B淋巴细胞的表达增加 ,其水平与疾病活动度有关。