二甲双胍联合糖皮质激素治疗伴糖耐量异常的系统性红斑狼疮患者的临床研究

目的: 探究二甲双胍联合糖皮质激素治疗伴糖耐量异常(IGT)的系统性红斑狼疮(SLE)患者的临床疗效及对胰岛功能、Th17/Treg细胞失衡的影响。方法: 本院84例伴IGT的SLE患者随机分为联用组和对照组各42例,均给予生活、饮食指导,对照组给予糖皮质激素治疗,联用组联合二甲双胍治疗,1个月后观察疗效,并评估胰岛功能和Th17/Treg细胞失衡情况。结果: 联用组总有效率明显高于对照组(90.48% vs. 71.43%,P<0.05),SLE活动指数评分为(2.6±0.3)分,红细胞沉降率(ESR)为(18±4)mm/h,显著低于对照组的(3.9±0.8)分、(23±4)mm/h(P<0.05)。治疗后联用组空腹血糖(FBG)、空腹胰岛素(Fins)、稳态模型-胰岛素抵抗指数(HOMA-IR)、胰岛β功能细胞指数(HOMA-β)显著改善(P<0.05),且与对照组相比差异有统计学意义(P<0.05);联用组正常糖耐量(NGT)占比明显高于对照组(73.81% vs. 30.95%,P<0.05)。治疗后联用组Th17、Treg细胞比例为(6.2±0.9)个/μL、(31±7)个/μL,Th17/Treg为(0.20±0.05),与对照组的(7.4±1.3)个/μL、(28±7)个/μL、(0.26±0.06)相比有统计学差异(P<0.05)。治疗后SLE活动指数评分与HOMA-IR、HOMA-β及Th17细胞、Treg细胞、Th17/Treg明显相关(P<0.05),且HOMA-IR、HOMA-β与Th17细胞、Treg细胞、Th17/Treg也明显相关(P<0.05)。2组不良反应均轻微,发生率无统计学差异(P>0.05)。结论: 二甲双胍联合糖皮质激素治疗伴IGT的SLE患者疗效显著,可控制疾病活动性,降低血糖水平、改善胰岛功能及纠正Th17/Treg细胞失衡,且安全性高。     

Externalizing lupus: A therapist/patient's challenge.

Coping with a serious and chronic illness poses unique challenges for individuals in helping professions. What techniques and resources can be used to help the helpers? A narrative framework using the process of externalizing the problem is presented as a potentially useful approach for psychotherapists experiencing a serious illness. The author describes her own experience with lupus and offers recommendations for therapists struggling to balance their professional responsibilities with their own personal needs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus

LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.     

Extracellular Vesicles Tune the Immune System in Renal Disease: A Focus on Systemic Lupus Erythematosus,Antiphospholipid Syndrome,Thrombotic Microangiopathy and ANCA-Vasculitis

Extracellular vesicles (EV) are microparticles released in biological fluids by different cell types, both in physiological and pathological conditions. Owing to their ability to carry and transfer biomolecules, EV are mediators of cell-to-cell communication and are involved in the pathogenesis of several diseases. The ability of EV to modulate the immune system, the coagulation cascade, the angiogenetic process, and to drive endothelial dysfunction plays a crucial role in the pathophysiology of both autoimmune and renal diseases. Recent studies have demonstrated the involvement of EV in the control of renal homeostasis by acting as intercellular signaling molecules, mediators of inflammation and tissue regeneration. Moreover, circulating EV and urinary EV secreted by renal cells have been investigated as potential early biomarkers of renal injury. In the present review, we discuss the recent findings on the involvement of EV in autoimmunity and in renal intercellular communication. We focused on EV-mediated interaction between the immune system and the kidney in autoimmune diseases displaying common renal damage, such as antiphospholipid syndrome, systemic lupus erythematosus, thrombotic microangiopathy, and vasculitis. Although further studies are needed to extend our knowledge on EV in renal pathology, a deeper investigation of the impact of EV in kidney autoimmune diseases may also provide insight into renal biological processes. Furthermore, EV may represent promising biomarkers of renal diseases with potential future applications as diagnostic and therapeutic tools.     

MicroRNA-155 Mediates Augmented CD40 Expression in Bone Marrow Derived Plasmacytoid Dendritic Cells in Symptomatic Lupus-Prone NZB/W F1 Mice

Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by hyperactivated immune responses to self-antigens and persistent systemic inflammation. Previously, we reported abnormalities in circulating and bone marrow (BM)-derived plasmacytoid dendritic cells (pDCs) from SLE patients. Here, we aim to seek for potential regulators that mediate functional aberrations of pDCs in SLE. BM-derived pDCs from NZB/W F1 mice before and after the disease onset were compared for toll-like receptor (TLR) induced responses and microRNA profile changes. While pDCs derived from symptomatic mice were phenotypically comparable to pre-symptomatic ones, functionally they exhibited hypersensitivity to TLR7 but not TLR9 stimulation, as represented by the elevated upregulation of CD40, CD86 and MHC class II molecules upon R837 stimulation. Upregulated induction of miR-155 in symptomatic pDCs following TLR7 stimulation was observed. Transfection of miR-155 mimics in pre-symptomatic pDCs induced an augmented expression of Cd40, which is consistent with the increased CD40 expression in symptomatic pDCs. Overall, our results provide evidence for miR-155-mediated regulation in pDC functional abnormalities in SLE. Findings from this study contribute to a better understanding of SLE pathogenesis and ignite future interests in evaluating the molecular regulation in autoimmunity.     

Environmental Factors,Toxicants and Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an immune-complex-mediated multi-systemic autoimmune condition of multifactorial etiology, which mainly affects young women. It is currently believed that the onset of SLE and lupus flares are triggered by various environmental factors in genetically susceptible individuals. Various environmental agents and toxicants, such as cigarette smoke, alcohol, occupationally- and non-occupationally-related chemicals, ultraviolet light, infections, sex hormones and certain medications and vaccines, have been implicated to induce SLE onset or flares in a number case series, case-control and population-based cohort studies and very few randomized controlled trials. Here, we will describe some of these recognized environmental lupus triggering and perpetuating factors and explain how these factors potentially bias the immune system towards autoimmunity through their interactions with genetic and epigenetic alterations. Further in-depth exploration of how potentially important environmental factors mechanistically interact with the immune system and the genome, which trigger the onset of SLE and lupus flares, will certainly be one of the plausible steps to prevent the onset and to decelerate the progress of the disease.     

微小RNA调控干扰素-α在系统性红斑狼疮发病机制中的作用

系统性红斑狼疮是一种多系统受累的自身免疫病。干扰素-α作为系统性红斑狼疮免疫紊乱的关键因素,对其作用机制及信号通路的研究可进一步揭示系统性红斑狼疮的发病机制,并为该病的临床治疗提供新策略。近年研究发现,微小RNA在系统性红斑狼疮发病机制中具有重要作用,且微小RNA异常表达参与Ⅰ型干扰素通路的调节。本文综述了微小RNA对Ⅰ型干扰素通路的调节及其在系统性红斑狼疮发病机制中的作用,对进一步认识系统性红斑狼疮的发病机制具有重要意义。     

神经精神性系统性红斑狼疮相关自身抗体的研究进展

神经精神性系统性红斑狼疮(NPSLE)的发病机制目前普遍认为是直接或间接的多种免疫机制作用的结果。NPSLE发病的不同表现形式与多种自身抗体相关,可能存在以下几种相关自身抗体:抗神经元抗体、抗磷脂抗体、抗NR2抗体、抗核糖体P蛋白抗体、抗微管相关蛋白2抗体、抗内皮细胞抗体、抗胶质原纤维酸性蛋白抗体。这些自身抗体可能成为提示或预测NPSLE的特异标记物,值得进一步探讨和证实。     

miR-499、miR-196a2、miR-149单核苷酸多态性与系统性红斑狼疮的关联性

目的：探讨系统性红斑狼疮（systemic lupus erythematosus,SLE）患者与 miR-499、miR-196a2及 miR-149单核苷酸多态性（single nucleotide polymorphism,SNP）的关联性。方法选取111例 SLE 患者（SLE 组）与120例健康者（对照组）为研究对象,收集临床资料并抽取2 mL 外周静脉血,提取基因组 DNA。利用 PCR-RFLP 技术对研究对象 miR-499 rs22928323、miR-196a2 rs11614913、miR-149 rs3746444的单核苷酸多态性进行检测,分析 SLE与 SNP 的关联性。结果miR-196a2 rs11614913表现为 TT、TC、CC 3种基因型,与 miR-196a2基因型 TT＋TC相比,基因型为 CC 的患者发病风险增加,OR＝1．28,95％CI 为1．03～1．84,P ＝0．017;miR-149 rs22928323表现为 TT、TC、CC 3种基因型,与 miR-149基因型 TT＋TC 相比,基因型为 CC 的患者发病风险不增加,OR ＝0．61,95％CI 为0．38～1．38,P ＝0．283;miR-499 rs3746444表现为 AA、AG、GG 3种基因型,与 miR-449基因型 AA＋AG 相比,基因型为 GG 的患者发病风险不增加,OR ＝0．78,95％ CI 为0．58～1．11,P ＝0．188。结论miR-196a2内的SNP rs11614913与中国华东地区人群 SLE 的遗传易感性有关;miR-499、miR-149内的 SNPs rs3746444、rs22928323与中国华东地区人群 SLE 的遗传易感性无关。