SLE B淋巴细胞靶向治疗进展

SLE的治疗是多方面的,B淋巴细胞靶向治疗是月前围内在临床上尚未普遍应用的新方法.国外临床试验结果初步证实具有良好有效性、安全性和耐受性,应用前景良好,从而为患者提供更多治疗选择,尤其是为那些对传统免疫抑制疗效不佳、无效或不良反应严重者带来希望.其确切疗效和长期的不良反应有待通过大规模临床试验及长期随访进一步得到验证.     

未成年系统性红斑狼疮患者与EB病毒感染的相关性研究

目的:探讨系统性红斑狼疮(SLE)与EB病毒(EBV)感染的相关性。方法:采用标准ELISA和聚合酶链反应(PCR)法检测117例未成年患者和153名正常对照的EBV感染情况。结果:116例患者和107名正常对照EBV-IgG阳性(P<0.001),患者和正常对照EBV-DNA阳性分别为32例和23例(P<0.02)。结论:EBV感染与SLE相关,EBV感染可能是SLE的病因之一。     

SLE患者外周血B淋巴细胞亚群Fas、bcl—2的检测

目的：探讨SLE中B淋巴细胞亚群的变化及其与细胞凋亡的关系。方法：用流式细胞仪双色解析法检测52例SLE患外周血CD19^ 、CD23^ B淋巴细胞亚群及其Fas、bcl-2的表达。结果：SLE患CD19^ 、CD23^ B淋巴细胞百分比高于正常对照,活动期高于稳定期;两细胞亚群Fas、bcl-2的表达率均高于正常对照,活动期高于稳定期,且CD23^ B淋巴细胞Fas的表达率高于CD19^ B淋巴细胞。结论：SLE患外周血B淋巴细胞过度增殖活化,其原因与B淋巴细胞的凋亡异常有关。     

SLE与EB病毒感染

ＳＬＥ与ＥＢ病毒感染有关，这种推测由来已久，但近年来国外一些学者才开始研究它们之间的关系，研究结果表明ＳＬＥ病人外周血循环中抗ＥＢ病毒的抗体滴度升高，并检测到ＥＢ病毒的几种抗原系统，发现ＳＬＥ病人的Ｂ淋巴细胞转化与ＥＢ病毒有关。推测ＥＢ病毒在ＳＬＥ的发生或发展中起一定作用。     

HSP-70在SLE中的表达及其与EB病毒感染的相关性

目的:探讨热休克蛋白-70(HSP-70)的表达与系统性红斑狼疮(SLE)发生、发展的关系及其与EB病毒感染的相关性。方法:采用逆转录聚合酶链反应(RT-PCR)方法,检测了60例SLE患者和30例正常对照组外周血单个核细胞中HSP-70的表达,酶联免疫吸附试验(ELISA)检测抗EB病毒核抗原IgG抗体的表达。结果:活动期患者HSP-70的表达明显高于稳定期组,稳定期组的表达明显高于对照组,其中活动期和稳定期患者中EB病毒感染阳性组HSP-70的表达均明显高于EB病毒阴性组。结论:EB病毒可能通过HSP-70的异常表达参与SLE的发病机制和病程。     

EB病毒潜伏基因表达与系统性红斑狼疮的关系

目的检测EB病毒(EpsteinBarrvirus,EBV)潜伏基因在EBV阳性系统性红斑狼疮(systemiclupuserythematosus,SLE)患者外周血单一核细胞中的表达,探讨其临床意义。方法应用聚合酶链反应(PCR)Southern杂交技术检测44例SLE患者和43例正常对照者外周血单一核细胞中EBV特异性DNA片段BamHⅠW,筛选出EBV阳性标本,对EBV阳性标本进行RTPCR和Southern杂交,检测病毒潜伏基因(EBV核抗原基因EBNA2,潜伏膜蛋白基因LMP1和2A)的表达。结果44例SLE患者标本中有32例EBV阳性,正常对照组有3例EBV阳性,两组EBV阳性率比较差异有显著性(χ2=39.1779,P=0),SLE活动期和稳定期患者EBV阳性率比较差异无显著性(q=0.4025,P=0.7764)。32例EBV阳性SLE标本中有20例EBNA2mRNA阳性,1例LMP1mRNA阳性,但均未检测到LMP2AmRNA的表达。结论EBV感染参与部分SLE的发生发展,EBV潜伏基因EBNA2的表达可能诱发SLE患者的自身免疫反应。     

脱氢表雄酮对SLE患者外周血淋巴细胞体外凋亡的影响

用放射免疫测定法和吖啶橙染色法分别检测３１例ＳＬＥ患者和２２名正常对照血清脱氢表雄酮水平和其在体外对淋巴细胞凋亡的影响。结果提示ＳＬＥ患者淋巴细胞的凋亡,结果提示ＳＬＥ患者体内淋巴细胞凋亡率高于正常,且ＤＨＥＡ水平的低下可能是导致ＳＬＥ患者淋巴细胞凋亡率升高的原因之一。     

EB病毒感染与系统性红斑狼疮发病关系的探讨

近年来,国内外一些学者^[1-4]开始研究Epstein-Barr病毒(EBV)感染与系统性红斑狼疮(SLE)发病的关系,发现SLE患者外周血循环中抗EB病毒的抗体滴度升高,并检测到EB病毒的几种抗原系统,认为SLE患者1的B淋巴细胞转化与EB病毒有关,EB病毒在SLE的发生或发展中可能起一定作用.我们采用聚合酶链反应(PCR)技术检测了48例SLE患者(其中活动期25例,非活动期23例)外周血中EB病毒DNA,现将检测结果报道如下.     

银屑病患者血清抗EB病毒抗体的检测

目的：探讨EB病毒感染与银屑病的关系。方法：采用酶免疫法检测53例银屑病患者血清EB病毒抗壳抗原／IgG、IgM抗体，抗早期抗原－D／IgG抗体。抗核心抗原－1／IgG抗体。结果：银屑病患者血清抗ER病毒早期抗原－D／IgG抗体阳性率明显高于正常对照组（P＜0．001）。结论：银屑病患者体内EB病毒可能处于激活状态。     

EB病毒蛋白对抗角蛋白自身抗体产生的影响

目的　研究EB病毒 (EBV)蛋白对B细胞产生抗角蛋白自身抗体 (AKautoAb)的影响。方法　用紫外线 (UV)灭活和热处理经EBV刺激培养的人脐带血B细胞 ,因ELISA法检测培养上清中AKautoAbIgG和IgM的水平。结果　UV灭活组IgG 18天以后各时间点有显著变化 (P <0 .0 5) ,IgM 2 6天与其它时间点有显著差异 (P <0 .0 5) ;热处理组IgG和IgM无明显变化 (P >0 .0 5)。结论　UV灭活EBV可诱导抗体的产生 ,而热处理EBV却不能 ,提示EBV蛋白成分可能是诱导抗体产生因素 ,这为深入研究影响AKautoAb产生的EBV功能蛋白奠定了基础     

SLE患者分泌IL-12水平的体外研究

目的了解SLE患者外周血单一核细胞(PBMC)、外周血淋巴细胞(PBL)和单核细胞分泌白细胞介素12(IL-12)的水平及PBMC分泌IL-12水平与SLE活动性的关系.方法体外培养PBMC、PBL和单核细胞,予LPS刺激后用夹心ELISA法检测其上清中的IL-12水平,用SLEDAI估计SLE的活动性.结果SLE患者PBMC分泌IL-12水平较正常对照低(P＜0.01),SLE患者和正常对照PBL分泌的IL-12差异无显著性(P＞0.05),而SLE患者的单核细胞分泌的IL-12水平则显著低于正常对照(P＜0.01).SLE患者PBMC分泌IL-12水平与SLEDAI呈负相关(P＜0.01).结论SLE患者PBMC分泌IL-12水平是降低的,在体外,SLE患者分泌IL-12水平降低是由单核细胞而不是B细胞的分泌能力降低引起的.且IL-12水平可作为评价SLE患者病情活动程度的参考指标.     

SLE患者外周血T、B淋巴细胞TLR9蛋白表达及与临床指标的关系

目的 探讨SLE患者外周血B、T淋巴细胞中Toll样受体9(TLR9)蛋白的表达水平及其与相关临床指标间的关系.方法 B、T淋巴细胞及TLR9蛋白各自用荧光抗体标记,用流式细胞仪测定35例新诊断但尚未经治疗的SLE患者及16例正常人对照外周血B、T淋巴细胞中TLR9蛋白的表达水平,分析TLR9蛋白表达水平与相关临床指标间的相关性.结果 SLE患者T、B淋巴细胞中表达TLR9蛋白的细胞百分比分别为(53.94±17.95)%、(49.33±23.30)%,对照组分别为(29.40±10.54)%、(29.18±14.78)%,两组相比差异有统计学意义(t值分别为6.11,3.73,P值均＜0.01).表达TLR9蛋白的B细胞百分比与SLEDAI成负相关(r=-0.39,P=0.02),与IgA表达量成正相关(r=0.74,P＜0.01).结论 初发未治型SLE患者TLR9蛋白表达水平较对照组升高,表达TLR9蛋白的B细胞百分比与SLEDAI成负相关,与IgA表达量成正相关.     

SLE患者外周血T、B淋巴细胞TLR9蛋白表达及与临床指标的关系

Objective To study the expressions of Toll-like receptor 9 protein (TLR9) in peripheral B and T lymphocytes in newly diagnosed, untreated patients with systemic lupus erythematosus (SLE) and their relationship with clinical parameters. Methods Blood samples were obtained from 35 newly diag-nosed, untreated patients with SLE and 16 healthy human controls. B, T lymphocytes and TLR9 protein were labeled with fluorescent antibodies, and the expressions of TLR9 protein were detected by flow cytometry in peripheral B and T lymphocytes. The relationship between TLR9 expression and clinical parameters was assessed. Results The proportions of B and T lymphocytes expressing TLR9 in newly diagnosed, untreated patients were (53.94±17.95)% and (49.33 ± 23.30)%, respectively, compared to (29.40 ± 10.54)% and (29.18 ± 14.78)%, respectively, in healthy controls (t = 6.11,3.73, respectively, both P < 0.01). Additionally,the proportion of B lymphocytes expressing TLR9 correlated negatively with SLE disease activity index (SLEDAI)(r = -0.39, P < 0.05), but positively with the level of serum IgA antibody (r = 0.74, P < 0.01).Condnsions The expression of TLR9 is elevated in peripheral T and B lymphocytes from patients with newly diagnosed, untreated SLE, and the proportion of TLR9-expressing B lymphocytes negatively correlates with SLEDAI, but positively correlates with the serum level of IgA antibody.     

SLE患者外周血T、B淋巴细胞TLR9蛋白表达及与临床指标的关系

Objective To study the expressions of Toll-like receptor 9 protein (TLR9) in peripheral B and T lymphocytes in newly diagnosed, untreated patients with systemic lupus erythematosus (SLE) and their relationship with clinical parameters. Methods Blood samples were obtained from 35 newly diag-nosed, untreated patients with SLE and 16 healthy human controls. B, T lymphocytes and TLR9 protein were labeled with fluorescent antibodies, and the expressions of TLR9 protein were detected by flow cytometry in peripheral B and T lymphocytes. The relationship between TLR9 expression and clinical parameters was assessed. Results The proportions of B and T lymphocytes expressing TLR9 in newly diagnosed, untreated patients were (53.94±17.95)% and (49.33 ± 23.30)%, respectively, compared to (29.40 ± 10.54)% and (29.18 ± 14.78)%, respectively, in healthy controls (t = 6.11,3.73, respectively, both P < 0.01). Additionally,the proportion of B lymphocytes expressing TLR9 correlated negatively with SLE disease activity index (SLEDAI)(r = -0.39, P < 0.05), but positively with the level of serum IgA antibody (r = 0.74, P < 0.01).Condnsions The expression of TLR9 is elevated in peripheral T and B lymphocytes from patients with newly diagnosed, untreated SLE, and the proportion of TLR9-expressing B lymphocytes negatively correlates with SLEDAI, but positively correlates with the serum level of IgA antibody.     

SLE患者外周血T、B淋巴细胞TLR9蛋白表达及与临床指标的关系

Objective To study the expressions of Toll-like receptor 9 protein (TLR9) in peripheral B and T lymphocytes in newly diagnosed, untreated patients with systemic lupus erythematosus (SLE) and their relationship with clinical parameters. Methods Blood samples were obtained from 35 newly diag-nosed, untreated patients with SLE and 16 healthy human controls. B, T lymphocytes and TLR9 protein were labeled with fluorescent antibodies, and the expressions of TLR9 protein were detected by flow cytometry in peripheral B and T lymphocytes. The relationship between TLR9 expression and clinical parameters was assessed. Results The proportions of B and T lymphocytes expressing TLR9 in newly diagnosed, untreated patients were (53.94±17.95)% and (49.33 ± 23.30)%, respectively, compared to (29.40 ± 10.54)% and (29.18 ± 14.78)%, respectively, in healthy controls (t = 6.11,3.73, respectively, both P < 0.01). Additionally,the proportion of B lymphocytes expressing TLR9 correlated negatively with SLE disease activity index (SLEDAI)(r = -0.39, P < 0.05), but positively with the level of serum IgA antibody (r = 0.74, P < 0.01).Condnsions The expression of TLR9 is elevated in peripheral T and B lymphocytes from patients with newly diagnosed, untreated SLE, and the proportion of TLR9-expressing B lymphocytes negatively correlates with SLEDAI, but positively correlates with the serum level of IgA antibody.     

SLE患者外周血T、B淋巴细胞TLR9蛋白表达及与临床指标的关系

Objective To study the expressions of Toll-like receptor 9 protein (TLR9) in peripheral B and T lymphocytes in newly diagnosed, untreated patients with systemic lupus erythematosus (SLE) and their relationship with clinical parameters. Methods Blood samples were obtained from 35 newly diag-nosed, untreated patients with SLE and 16 healthy human controls. B, T lymphocytes and TLR9 protein were labeled with fluorescent antibodies, and the expressions of TLR9 protein were detected by flow cytometry in peripheral B and T lymphocytes. The relationship between TLR9 expression and clinical parameters was assessed. Results The proportions of B and T lymphocytes expressing TLR9 in newly diagnosed, untreated patients were (53.94±17.95)% and (49.33 ± 23.30)%, respectively, compared to (29.40 ± 10.54)% and (29.18 ± 14.78)%, respectively, in healthy controls (t = 6.11,3.73, respectively, both P < 0.01). Additionally,the proportion of B lymphocytes expressing TLR9 correlated negatively with SLE disease activity index (SLEDAI)(r = -0.39, P < 0.05), but positively with the level of serum IgA antibody (r = 0.74, P < 0.01).Condnsions The expression of TLR9 is elevated in peripheral T and B lymphocytes from patients with newly diagnosed, untreated SLE, and the proportion of TLR9-expressing B lymphocytes negatively correlates with SLEDAI, but positively correlates with the serum level of IgA antibody.     

SLE患者外周血T、B淋巴细胞TLR9蛋白表达及与临床指标的关系

Objective To study the expressions of Toll-like receptor 9 protein (TLR9) in peripheral B and T lymphocytes in newly diagnosed, untreated patients with systemic lupus erythematosus (SLE) and their relationship with clinical parameters. Methods Blood samples were obtained from 35 newly diag-nosed, untreated patients with SLE and 16 healthy human controls. B, T lymphocytes and TLR9 protein were labeled with fluorescent antibodies, and the expressions of TLR9 protein were detected by flow cytometry in peripheral B and T lymphocytes. The relationship between TLR9 expression and clinical parameters was assessed. Results The proportions of B and T lymphocytes expressing TLR9 in newly diagnosed, untreated patients were (53.94±17.95)% and (49.33 ± 23.30)%, respectively, compared to (29.40 ± 10.54)% and (29.18 ± 14.78)%, respectively, in healthy controls (t = 6.11,3.73, respectively, both P < 0.01). Additionally,the proportion of B lymphocytes expressing TLR9 correlated negatively with SLE disease activity index (SLEDAI)(r = -0.39, P < 0.05), but positively with the level of serum IgA antibody (r = 0.74, P < 0.01).Condnsions The expression of TLR9 is elevated in peripheral T and B lymphocytes from patients with newly diagnosed, untreated SLE, and the proportion of TLR9-expressing B lymphocytes negatively correlates with SLEDAI, but positively correlates with the serum level of IgA antibody.     

SLE患者外周血T、B淋巴细胞TLR9蛋白表达及与临床指标的关系

Objective To study the expressions of Toll-like receptor 9 protein (TLR9) in peripheral B and T lymphocytes in newly diagnosed, untreated patients with systemic lupus erythematosus (SLE) and their relationship with clinical parameters. Methods Blood samples were obtained from 35 newly diag-nosed, untreated patients with SLE and 16 healthy human controls. B, T lymphocytes and TLR9 protein were labeled with fluorescent antibodies, and the expressions of TLR9 protein were detected by flow cytometry in peripheral B and T lymphocytes. The relationship between TLR9 expression and clinical parameters was assessed. Results The proportions of B and T lymphocytes expressing TLR9 in newly diagnosed, untreated patients were (53.94±17.95)% and (49.33 ± 23.30)%, respectively, compared to (29.40 ± 10.54)% and (29.18 ± 14.78)%, respectively, in healthy controls (t = 6.11,3.73, respectively, both P < 0.01). Additionally,the proportion of B lymphocytes expressing TLR9 correlated negatively with SLE disease activity index (SLEDAI)(r = -0.39, P < 0.05), but positively with the level of serum IgA antibody (r = 0.74, P < 0.01).Condnsions The expression of TLR9 is elevated in peripheral T and B lymphocytes from patients with newly diagnosed, untreated SLE, and the proportion of TLR9-expressing B lymphocytes negatively correlates with SLEDAI, but positively correlates with the serum level of IgA antibody.