白细胞介素12与系统性红斑狼疮

白细胞介素 12 (IL - 12 )在诱导T细胞向Th1类细胞分化过程中起关键性作用 ,可选择性抑制自身免疫性抗体分泌细胞B1细胞的增殖 .对系统性红斑狼疮 (SLE)患者的多种体外研究均说明 :IL - 12分泌减少在SLE患者细胞因子分泌异常及多克隆自身抗体产生中起重要作用     

白细胞介素12与系统性红斑狼疮

白细胞介素12(IL-12)在诱导T细胞向Th1类细胞分化过程中起关键性作用,可选择性抑制自身免疫性抗体分泌细胞B1细胞的增殖.对系统性红斑狼疮(SLE)患者的多种体外研究均说明:IL-12分泌减少在SLE患者细胞因子分泌异常及多克隆自身抗体产生中起重要作用.     

系统性红斑狼疮患者血清白细胞介素-18水平变化的意义

目的探讨系统性红斑狼疮（SLE）中白细胞介素-18（IL-18）的表达及其临床意义。方法应用双抗体夹心酶联免疫吸附实验（ELISA）方法分别测定50例SLE患者血浆的IL-18水平。结果SLE患者血清IL-18水平增高,活动期组较稳定期组增高明显（P〈0．05）,与正常对照组比较差异具有显著性（P〈0．05）。SLE患者治疗后IL-18水平低于治疗前水平（P〈0．05）。结论SLE患者血清IL-18水平显著增高,与SLE的病情活动密切相关,检测IL-18对SLE病情的判断有一定的价值。     

白细胞介素-18基因多态性与广西壮族系统性红斑狼疮的遗传易感性

目的 探讨白细胞介素-18(interleukin 18,IL-18)基因单核苷酸多态性与广西壮族系统性红斑狼疮(systematic lupus erythematosus,SLE)易感性之间的关系.方法 以115例SLE患者和160名健康对照者为研究对象,应用聚合酶链反应-限制性片段长度多态性和DNA测序的方法对IL-18基因-137G/C、-607C/A单核苷酸多态性进行基因分型.结果 IL-18基因-137G/C多态性在SLE组和正常人群中的分布差异无统计学意义(P>0.05),而IL-18基因-607C/A多态性在两组人群中的分布差异有统计学意义(P<0.05),等位基因频率的相对风险分析发现,-607 C等位基因携带者患系统性红斑狼疮的风险是-607A等位基因的1.619倍(OR=1.619,95%CI:1.150-2.281).联合基因型分析发现,IL-18的-137G/-607C等位基因频率在SLE组中显著高于对照组(P<0.05).-137G/-607C等位基因携带者显著增加了SLE的发病风险(OR=1.484,95%CI:1.056-2.087).结论 IL-18基因-607C/A多态性与SLE的发病具有相关性,其中-607 C等位基因可能是SLE的遗传易感基因.     

白细胞介素-17在神经系统疾病中的作用

白细胞介素(IL)-17是一种新型的炎性细胞因子,主要由Th17细胞分泌,可诱导其它细胞因子及趋化因子的生成,并刺激中性粒细胞的募集及活化参与炎症反应及免疫应答.随着对于IL-17的深入研究,人们发现其可能在脑炎、癫痫、自身免疫性疾病、脑肿瘤等神经系统疾病中发挥了重要的作用.     

IL—10在系统性红斑狼疮发病机制中的角色

系统性红斑狼疮的B细胞过度活化,细胞介导的免疫应答受损。而IL－10既是有效的B细胞刺激因子,又能抑制T细胞和抗原递呈细胞的功能,在SLE发病机制的免疫调节紊乱中扮演重要角色：IL－10的基因与SLE易感性有关,在SLE病人的健康亲属体内IL－10也呈高表达,该因子还参与疾病状态下的细胞因子谱偏移及细胞凋亡异常。IL－10分泌增加与狼疮环境的形成密切相关。     

系统性红斑狼疮患者外周血白细胞介素15的研究

目的：检测系统性红斑狼疮（SLE）患者血清白细胞介素15（IL-15）水平及外周血单个核细胞（PBMC）IL-15mRNA表达，并进一步分析其临床意义。方法：IL-15检测采用ELISA方法；PBMCIL-15mRNA表达采用原位杂交法检测。结果：①SLE组患者血清IL-15水平显著高于正常对照组（P〈0．01），活动期SLE患者血清IL-15水平显著高于缓解期患者（P〈0．05）。②发生临床肾损害者IL-15水平明显高于无肾损害者（P〈0．05），出现血清抗dsDNA抗体阳性、低补体C3血症、高IgG血症者血清IL-15水平均分别显著高于无上述表现者。③SLE患者PBMCIL-15mRNA表达量明显高于正常对照组（P〈0．05），活动期SLE显著高于缓解期（P〈0．05）。④SLE患者PBMC培养上清IgG、IgM和抗dsDNA抗体浓度均显著高于正常对照组；SLE患者PBMCIL-15mRNA表达量与细胞培养上清的IgG及抗dsDNA抗体滴度均呈正相关关系（分别为r=0．645和r=0．715，P〈0．05），而与IgM．无相关关系（r=0．451，P〉0．05）。⑤SEE患者PBMCIL-15mRNA表达量与血清IL-15水平呈正相关关系（r=0．726，P〈0．05）。结论：SLE患者存在外周血IL-15蛋白和基因表达异常，且与其分泌免疫球蛋白和自身抗体有关，提示IL-15可能参与SLE的病理生理过程。     

Th17细胞及IL-17与系统性红斑狼疮

系统性红斑狼疮（SLE）是多种因素相互作用引起的自身免疫性疾病,其发病机制复杂。Th17细胞是最近发现的CD4^＋效应T细胞的新亚群。初始T细胞在TGF—B和IL-6的共同作用下分化发育成为Th17细胞,后者可以分泌IL-17、IL-21、IL-22等多种细胞因子。其中IL-17在多种自身免疫疾病（比如类风湿关节炎和Crohn’s病）中起关键作用,但在SLE中的作用尚不清晰。     

Serum interleukin-17 levels are associated with nephritis in childhood-onset systemic lupus erythematosus

OBJECTIVES:

To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment.

METHODS:

We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits.

RESULTS:

The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63).

CONCLUSION:

IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus.     

Th17细胞在系统性红斑狼疮免疫炎症反应中的作用机制研究

目的从Th17/Treg、IL-17及RORγt mRNA表达3方面进行研究,探讨Th17细胞在SLE免疫炎症反应中的作用机制。方法研究对象为26例活动期SLE患者、16例非活动期SLE患者和20例正常对照,采用细胞内染色流式细胞术检测Th17/Treg,ELISA法检测IL-17及RT-PCR法检测RORγt mRNA表达,并探讨它们与SLE疾病活动性的关系。结果活动期SLE患者组Th17/Treg、IL-17及RORγt mRNA表达水平显著高于非活动期及正常对照组;非活动期SLE患者组RORγt mRNA表达显著高于正常对照组,但两组间Th17/Treg、IL-17水平无显著差异。SLE患者Th17/Treg、IL-17及RORγt mRNA表达水平均与和SLEDAI呈正相关。结论 SLE患者存在着Th17细胞高表达现象,阻断Th17细胞分化的上游或下游均可能减轻SLE的免疫炎症反应而达到治疗SLE的目的。     

白细胞介素17 在狼疮性肾炎小鼠中的表达及抗白细胞介素17抗体的干预作用

 目的:探讨白细胞介素17（IL-17）在狼疮性肾炎(LN）小鼠中的表达及抗IL-17抗体的干预作用。方法:11周龄的雌性MRL/lpr小鼠36只随机分为实验组和干预组,另有同龄雌性昆明小鼠18只为对照组。干预组每只小鼠腹腔注射抗小鼠IL-17多克隆抗体20 μg,每2周1次,至实验观察点结束。各组分别于第1次给药后的24 h、14 d及28 d处死6只小鼠。光镜下观察肾脏病理情况,ELISA法检测小鼠血清IL-17的含量,免疫组化法检测肾组织IL-17的表达水平。结果:MRL/lpr小鼠肾小球系膜细胞及基质弥漫增生,肾小管上皮细胞颗粒及空泡变性,灶状萎缩,肾间质淋巴及单核细胞浸润伴纤维化;而干预组肾脏病理改变较实验组为轻。MRL/lpr小鼠的血清IL-17含量在实验组各时点均显著高于对照组（P<0.05）,而在干预组各时点均显著低于实验组（P<0.05）。IL-17在实验组小鼠肾小管上皮细胞中的表达明显增强,在各时点均显著高于对照组（P<0.05）;在干预组,IL-17在各时点的表达均显著低于实验组（P<0.05）。结论:IL-17在MRL/lpr小鼠血清与肾组织中的表达显著增加,而抗IL-17抗体可通过抑制IL-17的表达而抑制LN的炎症免疫反应,减轻肾脏病理损害。     

DNA甲基化与系统性红斑狼疮

系统性红斑狼疮是一种针对自身抗原产生自身抗体从而形成免疫复合物为特征的慢性炎症性的自身免疫性疾病,能够累及机体的多个脏器(以皮肤、关节、肾脏受累为多见).系统性红斑狼疮的发病机制涉及到环境、遗传、性别多个因素的相互作用,对于哪个因素在其中起着关键性的作用,是如何诱发疾病的发生,以及在发病过程中的具体作用机制到目前来说还没有一个统一认识.目前许多研究表明,DNA的甲基化可以作为环境、性别等因素的共同作用通路在狼疮的发病中起到一定的作用,现就关于DNA的甲基化与系统性红斑狼疮的关系做一综述.     

Interleukin-17 in systemic lupus erythematosus: A comprehensive review

Abstract

Systemic lupus erythematosus (SLE) is a complicated autoimmune disease of multifactorial pathoaetiology. One of the most serious manifestations is lupus nephritis. The pathogenesis of SLE has not been well elucidated, but it has been reported that interleukin-17 (IL-17) and Th17 cells play important roles in the pathogenesis of SLE. IL-17A, a member of IL-17 family, amplifies the immune response by inducing the local production of chemokines and cytokines, recruiting neutrophils and monocytes, augmenting the production of autoantibodies, and aggravating the inflammation and damage of target organs such as the kidney in SLE. In recent years, several IL-17A pathway inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibody and the anti-17RA monoclonal antibody. Several agents have shown great success in Phase II trials in multiple autoimmune diseases such as psoriasis, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, and non-infectious uveitis, which has sparked the urgent need of anti-IL-17A as innovative therapeutic option in controlling disease activity of moderate-to-severe SLE. Here, we review and summarize current progress in IL-17A and SLE from in vitro studies, human expression studies, and animal models, providing novel insight into its therapeutic potential.     

T helper cell dysfunction in systemic lupus erythematosus (SLE): Relation to disease activity

Patients with systemic lupus erythematosus (SLE) are known to have defects in both humoral and cellular immunity. The significance of defective T cell-mediated immunity and its relationship to disease activity have not been clearly established. We studiedin vitro T helper cell (Th) function in 150 SLE outpatients and correlated Th function with validated measures of disease activity. Interleukin 2 (IL-2) production by peripheral blood mononuclear cells (PBMC) was measured after stimulation with the recall antigens influenza A virus (FLU) and tetanus toxoid (TET), irradiated allogeneic peripheral blood mononuclear cells (ALLO), and phytohemagglutinin (PHA). We observed three patterns of Th response: (1) 76 of 150 (50%) of patients responded to the recall antigens FLU and/or TET, ALLO, and PHA; (2) 62 of 150 (42%) of patients did not respond to recall antigens but responded to ALLO and PHA; and (3) 12 of 150 (8%) of patients did not respond to either recall antigens or ALLO antigens. This diminished T cell function was correlated with higher disease activity as measured by four scales of clinical activity, such that individuals who exhibited morein vitro immune dysfunction presented with significant increases in their clinical activity indicies. The alterations in T cell function could not be accounted for by medication doses alone. Thus, SLE patients have multiple distinct defects at the level of the Th cell which are associated with clinical measures of disease activity.     

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.     

DNaseI in pathogenesis of systemic lupus erythematosus

The aberrant activation of lymphocytes causes autoimmune diseases. Although there are many candidate molecules that are involved in the pathogenesis of autoimmune diseases, it still remains unclear how immunological tolerance is disturbed in each autoimmune disease. Recently, we discovered two patients suffering from systemic lupus erythematosus (SLE) with a defect in the DNaseI gene locus. According to immunological and genetic analysis, we hypothesize that defective antigen clearance, especially accumulation of nucleosomal antigens, is responsible for the development of SLE. In this article, we review the pathogenesis of SLE from the view of defective self-antigen clearance due to low DNaseI activity.     

Prognosis of neonates in pregnant women with systemic lupus erythematosus

PURPOSE: The effects of maternal systemic lupus erythematosus (SLE) on neonatal prognosis were examined by comparing clinical features of full-term babies born to lupus mothers and age- and parity-matched controls. PATIENTS AND METHODS: From January 2000 to December 2005, 39 singletons were born to 37 SLE women. Excluding 11 cases of prematurity and preeclampsia, 28 full-term neonates formed the lupus group. The control group included 66 full-term babies. The retrospective study examined medical records and compared gestational age, birth weight, days of hospital stay, small for gestational age (SGA) frequency, Apgar scores < 7, and parity. Lupus neonates were tested for anti-nuclear antibody (ANA) and platelet count, and electrocardiogram was performed. RESULTS: Average gestational age (38 vs. 39 weeks, p < 0.05) and birth weight (2,775 vs. 3,263g, p < 0.05) were significantly different between the SLE and control groups. SGA frequency was higher in the SLE group (25% vs. 4.5%, p < 0.05). No significant difference was observed in Apgar score, birth weight, gestational age, SGA frequency, and platelet count between lupus subgroups formed based on anti-dsDNA antibody levels and antiphospholipid antibody status. CONCLUSION: The association of maternal ANAs, antiphospholipid antibodies, and drug history with neonatal prognosis could not be elucidated. However, even in uncomplicated pregnancies, maternal lupus is disadvantageous for gestational age, birth weight, and SGA frequency.