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。     

Brain diffusion tensor MRI in systematic lupus erythematosus: A systematic review

Diffusion tensor imaging (DTI) maps the brain's microstructure by measuring fractional anisotropy (FA) and mean diffusivity (MD). This systematic review describes brain diffusion tensor Magnetic resonance imaging (MRI) studies in systemic lupus erythematosus (SLE).The literature was reviewed following the PRISMA guidelines and using the terms “lupus”, “systemic lupus erythematosus”, “SLE”, “diffusion tensor imaging”, “DTI”, “white matter” (WM), “microstructural damage”, “tractography”, and “fractional anisotropy”; the search included articles published in English from January 2007 to April 2017. The subjects included in the study were selected according to the ACR criteria and included 195 SLE patients with neuropsychiatric manifestation (NPSLE), 299 without neuropsychiatric manifestation (non-NPSLE), and 423 healthy controls (HC). Most studies identified significantly reduced FA and increased MD values in several WM regions of both NPSLE and non-NPSLE patients compared to HC. Subclinical microstructural changes were observed in either regional areas or the entire brain in both the non-NPSLE and NPSLE groups.     

Protective effects of quercetin treatment in a pristane-induced mouse model of lupus nephritis

Introduction: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus. As murine models of LN are valuable tools to better understand its pathophysiology and to search for new effective treatments, we investigated the effects of the bioflavonoid quercetin on pristane-induced LN mice through histomorphological analyses.

Methods: Immunofluorescence and biochemical assays were used to evaluate the expression of markers of inflammation (interleukin-6, IL-6; tumour necrosis factor-α, TNF-α), oxidative stress (catalase, CAT; superoxide dismutase 1, SOD1; thiobarbituric acid reactive substances, TBARS), apoptosis (Bax), and fibrosis (transforming growth factor-β1, TGF-β1). Glomerular and tubular ultrastructure was analysed, and tissue messenger RNA of podocin, podoplanin and α3β1-integrin were quantified using the real-time polymerase chain reaction.

Results: Pristane-induced LN mice showed severe kidney injury, characterized by increased proteinuria, glomerular mesangial expansion and inflammation, high expression of the pro-fibrotic, apoptotic and prooxidant markers and reduction of antioxidants. In the kidney ultrastructure, foot process (FP) effacement, apoptotic mesangial cells and abnormal mitochondria with disrupted cristae were observed, along with suppressed tissue mRNA of podocin, podoplanin and α3β1-integrin. Treatment with quercetin in the pristane-induced LN mice model was nephroprotective, decreasing proteinuria levels and significantly lowering tissue expression of IL-6, TNF-α, TGF-β1, Bax and TBARS. Simultaneously, quercetin significantly increased CAT and SOD1 expressions in these mice. In addition, it was observed improvement of the kidney ultrastructure, and tissue mRNA of podocin, but not podoplanin and α3β1-integrin, was restored to the levels found in the control mice.

Conclusion: In conclusion, these findings provide experimental evidence of the renoprotective effects of quercetin in the pristane-induced LN mice model. We suggest that quercetin effectively ameliorates the kidney damage caused by pristane, a bioflavonoid to be further evaluated as a new therapeutic strategy in this disease.     

狼疮性肾炎患者肾组织Epstein-Barr病毒感染状况及其致病作用初探

并感染之间以及不同病理类型之间差异均无统计学意义(P＞0.05).肾组织EBER和EBV LMP1表达阳性的LN患者的血清中anti-Sm-Ab阳性率显著高于两标记物表达阴性的LN患者(EBER:34.3%vs 8.7%,EBV LMP1:35.3%vs 9.1%,P均＜0.05).结论 肾组织EBV感染可能参与了LN的发病,其机制可能部分与诱导机体产生自身抗体anti-Sm-Ab有关.     

HMGB1在系统性红斑狼疮肾损害中的作用

目的 研究高迁移率族蛋白1(high mobility group protein box 1,HMGB1)在系统性红斑狼疮肾损害中的作用.方法 ELISA检测12例健康对照、16例系统性红斑狼疮(systemic lupus erythematosus,SLE)无肾脏损害和14例合并肾脏损害的系统性红斑狼疮患者(lupus nephritis,LN)血清中HMGB1的表达情况.将体外培养的人系膜细胞分为正常对照组和HMGB1刺激组,于培养6、12、24 h后收集细胞,免疫细胞化学检测增殖细胞核抗原(PCNA)的表达变化;免疫细胞化学和流式细胞术检测Toll样受体2(TLR2)、NF-κB 065蛋白的表达变化.结果 血清中HMGB1蛋白在LN组明显高于SLE组和健康对照组,且血清中HMGB1水平与LN患者的蛋白尿呈显著正相关;人重组HMGB1能够促进系膜细胞增殖;与正常对照组相比,HMGB1刺激组中TLR2、NF-κB p65蛋白表达增强;TLR2蛋白与NF-κB p65蛋白表达呈显著正相关(r=0.658,P=0.000);NF-κB p65蛋白表达与PCNA阳性表达率呈显著正相关(r=0.536,P=0.007).结论 HMGB1是狼疮性肾炎发病中的重要的细胞因子之一,可能部分通过与其受体蛋白TLR2结合激活NF-κB促进系膜细胞增生,从而引起肾脏损害.     

77例神经精神狼疮患儿临床分析

目的 分析神经精神狼疮(NPSLE)患儿的临床特点.方法 回顾性分析77例NPSLE患儿的临床表现、实验室检查、神经影像学特征、治疗及预后,并采用Logistic回归模型分析相关指标与NPSLE复发的关系.结果 本组系统性红斑狼疮(SLE)患儿NPSLE患病率为17.3%,75%患儿发病后2年以内出现NPSLE.其表现形式多种多样,最常见的症状是头痛(31.8%),其次足癫痫样发作(29.1%).活动期92.2%患儿SLE疾病活动指数(SLEDAI)评分≥15分,表现为重症狼疮.常伴有发热(88.3%)、皮疹(84.4%),最易同时受累的系统包括肾脏(76.6%)、血液系统(67.5%).与其他实验窜指标相比,NPSLE急性期抗核抗体(ANA)阳性率最高(98.7%),其次是血沉增快(86.3%)和补体降低(72.7%).90.1%腰椎穿刺结果异常,60.7%头颅CT异常,54.8%头颅磁共振成像异常,73.9%脑电图异常.常规治疗采用糖皮质激素加免疫抑制剂治疗,79.2%联合应用大剂量甲泼尼龙冲击治疗;51.9%疾病急性期进行了甲氨蝶呤+地塞米松联合鞘内注射治疗;26.0%急性期应用了静脉免疫球蛋白治疗;2例患儿进行了自体外周血干细胞移植治疗.住院死亡率9.0%,NPSLE复发率22.0%,75.0%患儿24个月内复发.SLEDAI评分对预测NPSLE复发有显著意义(X2=3.987,P=0.0459,OR=1.172,95%CI 1.003～1.370).结论 本研究初步探讨了儿童NPSLE患者的临床特点,分析了可能导致NPSLE复发的相关因素,为进一步认识及合理治疗儿童NPSLE奠定了基础.     

Pre-existing CD19-independent GL7− Breg cells are expanded during inflammation and in mice with lupus-like disease

Interleukin 10 (IL-10)-producing regulatory B-cells (Bregs) suppress inflammatory responses that mediate autoimmune diseases. However, it is unknown whether Bregs derive from a pre-existing dedicated B-cell lineage or if any B-cell can differentiate into Bregs in response to BCR or TLR activation. GL7⁺ B-cells are antigen-experienced differentiated B-cells while GL7^−/lo are at an early stage of B-cell differentiation. While both GL7^−/lo and GL7⁺ B cells can produce IL-10, differentiation of GL7⁻ B-cells into Bregs does not require CD19- or Bcl6-induced signals, suggesting that BCR-induced proliferation or Ig class-switching is not necessary for generation of Breg cells. Of particular importance, we show that GL7⁻ Breg cells are dramatically expanded in lupus-like mice and GL7⁻ Bregs suppressed inflammatory responses in lupus-like mice by inducing expansion of Foxp3⁺Treg cells. Taken together, these results suggest that pre-existing GL7⁻IL-10⁺ cells are expanded during inflammation, differentiate into GL7⁺ Bregs and contribute to immune-regulation in lupus-like mice.     

Characterization of Anti-Mesangial Cell Antibodies and Their Target Antigens in Patients with Lupus Nephritis

The pathogenetic mechanisms of lupus nephritis (LN) remain to be elucidated. In our previous study, autoantibodies against human glomerular mesangial cells (HMC) were identified in sera of most patients with lupus nephritis. The current study is to investigate the binding characteristics of anti-mesangial cell antibodies to human mesangial cell membrane. Serum samples were collected from 54 patients with renal biopsy proven lupus nephritis, 12 patients with systemic lupus erythematosus without clinical renal involvement, and 15 healthy subjects. Membrane proteins were obtained from in vitro cultured HMC by sonication and sequential centrifugation. DNase I were employed to remove DNA fragments in sera and membrane protein preperation and IgG F(ab′)₂ was obtained by pepsin digestion. Western Blot analysis was used to characterize the antibody and antigen interaction. In results, 25 of 54 (46.3%) sera from patients with lupus nephritis had anti-mesangial cell antibodies targeted at 74 kDa, 63 kDa, 52 kDa and 42 kDa protein bands of HMC membrane. Only four of 12 (33.3%) sera from patients without renal involovement recognized the protein bands at 74 kDa and 63 kDa, but not 52 kDa and 42 kDa. DNase treatment of the HMC membrane and the sera did not affect the binding. IgG F(ab′)₂ from sera of 10 patients with positive anti-mesangial cell antibodies could still bind the 63 kDa protein. In conclusion, anti-mesangial cell antibodies from sera of patients with lupus nephritis could bind membrane proteins of HMC directly without a DNA bridge and the binding was through antigen–antibody interation. Anti-mesangial cell antibodies might play some role in the pathogenesis of lupus nephritis(LN).     

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.