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。     

Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains

Systemic lupus erythematosus (SLE) is an autoimmune disorder of a largely unknown etiology. Anti-double-stranded (ds) DNA antibodies are a classic hallmark of the disease, although the mechanism underlying their induction remains unclear. We demonstrate here that, in both lupus-prone and normal mouse strains, strong anti-dsDNA antibody responses can be induced by dendritic cells (DC) that have ingested syngeneic necrotic (DC/nec), but not apoptotic (DC/apo), cells. Clinical manifestations of lupus were evident, however, only in susceptible mouse strains, which correlate with the ability of DC/nec to release IFN-gamma and to induce the pathogenic IgG2a anti-dsDNA antibodies. Injection of DC/nec not only accelerated disease progression in the MRL/MpJ-lpr/lpr lupus-prone mice but also induced a lupus-like disease in the MRL/MpJ-+/+ wild-type control strain. Immune complex deposition was readily detectable in the kidneys, and the mice developed proteinuria. Strikingly, female MRL/MpJ-+/+ mice that had received DC/nec, but not DC/apo, developed a 'butterfly' facial lesion resembling a cardinal feature of human SLE. Our study therefore demonstrates that DC/nec inducing a Th1 type of responses, which are otherwise tightly regulated in a normal immune system, may play a pivotal role in SLE pathogenesis.     

Aberrant B1 cell migration into the thymus results in activation of CD4 T cells through its potent antigen-presenting activity in the development of murine lupus

B1 cells have different origin and function from conventional B (B2) cells and are considered to be involved in autoantibody production in the development of autoimmune disease. We found that B1 cells preferentially accumulated in the target organs including thymus in aged BWF1 mice, a murine model for systemic lupus erythematosus, and that B lymphocyte chemoattractant (BLC/CXCL13) expression was increased in the thymus before the onset of lupus nephritis, while stromal cell-derived factor-1 (SDF-1/CXCL12) and secondary lymphoid tissue chemokine (SLC/CCL21) expression remained unchanged. Adhesion molecules such as peripheral node addressin (PNAd), ICAM-1, and VCAM-1 were also expressed on endothelial cells in the enlarged thymic perivascular space (PVS) in aged BWF1 mice. BLC protein and PNAd were co-localized on these high-endothelial-venules-like vessels in enlarged PVS. B1 cells expressed higher level of costimulatory molecules and showed a potent antigen-presenting activity in allogeneic mixed lymphocyte reaction comparable to splenic dendritic cells. Interestingly, B1 cells stimulated proliferation of autologous thymic CD4 T cells in the presence of IL-2. These results indicate that aberrant B1 cell trafficking into the thymus due to ectopic high expression of BLC may result in an activation of self-reactive T cells in the development of murine lupus.     

Successful treatment of refractory thrombocytopenia with mycophenolate mofetil in a patient with systemic lupus erythematosus

While mild thrombocytopenia in systemic lupus erythematosus (SLE) is frequently seen in the context of active disease, severe thrombocytopenia causing significant bleeding is not that common. Corticosteroids are considered the first line therapy for severe thrombocytopenia in SLE. Second-line therapeutic agents or splenectomy have been reported to be effective for patients who fail to respond to steroids or those who require moderate doses of steroids to maintain the platelet counts. Recent randomized controlled studies have shown that mycophenolate mofetil (MMF) is an efficacious and safe therapeutic agent in patients with proliferative forms of lupus nephritis. However, little information has been available regarding the role of MMF in the treatment of immune thrombocytopenia complicated with SLE. Hereby I describe a patient with SLE in whom thrombocytopenia was refractory to corticosteroids, intermittent intravenous cyclophosphamide, azathioprine, cyclosporine, intravenous gamma globulin, danazol, and splenectomy, and whose platelet counts eventually normalized during therapy with MMF. In this patient, thrombocytopenia is initially thought to be associated with active SLE involving major organ. However, after immunosuppressive agents were given, the refractory nature of thrombocytopenia seems to be an isolated phenomenon, independently of SLE activity.     

Histiocytic necrotizing lymphadenitis without granulocytic infiltration

Summary Twenty-seven cases of an unusual necrotizing lymphadenitis previously described only in Japan are reported as occurring in West Germany (23 cases), Iran (1 case), Italy (1 case), Korea (1 case) and Spain (1 case). The lesion frequently develops in the cervical lymph nodes of young women. It is characterized by infiltration of the cortex and/or paracortex by large collections of proliferating histiocytes and is devoid of granulocytes. Complete or, more often, incomplete necrosis of lymphoid tissue is seen in all cases. In cases with incomplete necrosis, the histiocytes are interspersed with pyknotic cells and nuclear debris. Based on the histological findings, the term histiocytic necrotizing lymphadenitis without granulocytic infiltration is proposed. Lesions to be considered in a differential diagnosis are malignant histiocytic neoplasms and necrotizing lymphadenitis with granulocytic infiltration, which is seen in lupus erythematosus and bacterial infections. The aetiology of histiocytic necrotizing lymphadenitis without granulocytic infiltration is still unclear. Some clinical and histological features indicate the possibility of an underlying viral infection.This study was supported by the Kind-Philipp-Stiftung     

Anti-SM and anti-U1-RNP lupus antibody fine specificities

Evidence for the presence of multiple shared epitopes on the target cellular antigens was found when 290 anti-Sm and anti-U1-RNP lupus sera were analyzed by immunoblotting. Forty-eight different immunoblot patterns were observed with the sera. Studies with selected antigenaffinity-purified antibodies confirmed the presence of multiple shared epitopes, in agreement with findings obtained with monoclonal antibodies. The results have implications for the design of effective diagnostics and for the use of these antibodies as molecular probes.     

氟达拉宾对系统性红斑狼疮BXSB小鼠狼疮活动的影响

目的 :探讨氟达拉宾对系统性红斑狼疮BXSB小鼠狼疮活动的影响 ,氟达拉宾治疗重型系统性红斑狼疮的可能性、有效性及其可能的机制。方法 :用 30mg (m2 ·d) ,连续 3天氟达拉宾尾静脉注入BXSB小鼠体内 ,用血液分析仪分析用氟达拉宾前后不同时间小鼠外周血白细胞的变化 ,用ELISA方法测定BXSB小鼠血清抗ds DNA抗体、抗核抗体的变化 ,免疫荧光检查肾组织的病理改变 ,尿蛋白试纸检测用氟达拉宾前后BXSB小鼠的蛋白尿 ,流式细胞仪分析T淋巴细胞表面CD4 + Fas+ 、CD8+ Fas+ 、、CD4 5RO+ Fas+ 表达的变化。结果 :用氟达拉宾后BXSB小鼠外周血白细胞数从第 3天开始下降 ,至第 7天时白细胞下降至最低值〔(0 5± 0 2 )× 10 9L- 1 〕 ,白细胞上升至 1 0× 10 9L- 1 的时间是用药后 19天 ;BXSB小鼠血清抗ds DNA抗体、抗核抗体的水平明显下降 ,分别出现在用氟达拉宾后第 14、2 1天时 ;用药后第 2 8天氟达拉宾组 72 7%的BXSB小鼠肾组织进行免疫荧光病理检查 ,其荧光强度由 +～ ++→± ;用氟达拉宾后第 2 1、2 8天尿蛋白从 ++～ +++转±～ -占 81 8% ;用Flu后BXSB小鼠CD4 + Fas+ 、CD8+ Fas+ 、CD4 5RO+ Fas+ 的表达均明显低于用Flu前。结论 :氟达拉宾可明显减少BXSB小鼠血清抗ds DNA抗体、抗核抗体的水平 ,减少BXSB小     

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.     

全身性红斑狼疮、银屑病和胰岛素依赖性糖尿病病人补体成份BfSS亚型的检测

用薄层聚丙烯酰胺凝胶等电聚焦方法对62例全身性红斑狼疮(SLE)、61例寻常型银屑病(PV)及17例胰岛素依赖性糖尿病(IDDM)病人补体第二途径成份B因子SS型的亚型分布及基因频率进行了检测。结果表明,SLB病人BfSS亚基因频率分别为,S_A0.516,S_B0.484;PV为:S_A0.492,S_B0.508,IDDM为:S_A0.676,S_B0.324。与正常人(S_A0.414,S_B0.586)比较,三种疾病的S_A亚基因频率均有不同程度的增高,并伴有S_B亚基因频率的降低。统计结果表明,IDDM与正常人的差异显著(P<0.01),SLE次之(P<0.05),PV不著(P>0.1)。此外,这三种疾病病人BfS_A-S_A亚型的表型频率(分别为30.6%、31.1%和41.1%)都显著高于正常19.3%),统计学表明差异均显著(P<0.05)。     

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.