MCP-1及IL-10在狼疮性肾炎及其相关疾病活动度的临床意义

目的:分析活动期和静止期狼疮性肾炎(LN)患者血清和尿液标本中单核细胞趋化蛋白-1(MCP-1)和IL-10水平的变化并探讨其临床意义。方法:应用ELISA技术对活动期和静止期LN患者血清和尿液中MCP-1和IL-10进行检测,分析LN不同时期MCP-1和IL-10与其他相关指标之间的关系。结果:活动期患者尿液MCP-1水平显著地高于静止期患者,而血清MCP-1两者差异无统计学意义;活动期患者血清IL-10水平显著地高于静止期患者,而尿液IL-10两者差异无统计学意义。结论:尿液MCP-1和血清IL-10水平可能与LN活动存在一定的相关性,有望成为SLE肾脏损害及疗效观察的监测指标。     

湖北省汉族人群甘露糖结合凝集素基因启动子区多态性与SLE关联性的研究

甘露糖结合凝集素 (mannose bindinglectin ,MBL)是一种由肝脏合成和分泌的急性期蛋白 ,可激活补体 ,溶解病原菌〔1〕,并具有调理吞噬作用。是参与非特异性免疫防御的重要分子。MBL基因启动子区具有两个多态性位点 :H L( 5 5 0bp ,G C)和X Y( 2 2 1bp ,C G) ,可影响MBL基因的转录 ,降低血清中MBL的浓度。已证明启动子的单元型HY、LY、LX分别与血清中高、中、低水平的MBL相关〔2〕。系统性红斑狼疮 (SLE)的发病与抗原 抗体复合物的清除缺陷有关。由于MBL基因启动子区的多态性可影响MBL的基因转录及其在血清中的浓度 ,从而影…     

MCP-1的表达与动脉粥样硬化

单核细胞趋化蛋白１（ＭＣＰ－１）能趋化单核细胞在内皮下间隙聚集，这是动脉粥样硬化最早期的病变之一，近年研究表明，内皮细胞、平滑肌细胞、单核细胞和巨噬细胞均能表达ＭＣＰ－１。并认为动脉粥样硬化病变早期的内皮细胞和内皮下巨噬细胞是ＭＣＰ－１的主要来源。     

ICAM-1基因K469E与MCP-1基因-2518A/G多态性的交互作用和胃癌侵袭与转移的关系

目的:探讨细胞间黏附分子1(intercellular adhesion molecule-1,ICAM-1)基因K469E与单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)基因-2518A/G多态性的交互作用和胃癌侵袭与转移的关系。方法:依据TNM分期,选择我院2009年12月至2014年11月收治的胃癌患者4 500例,分为胃癌Ⅰ期组、Ⅱ期组、Ⅲ期组、Ⅳ期组及0期组各900例,各组在年龄、性别、民族、籍贯和生活习惯方面无显著差异,以上述各组患者的外周血白细胞为样本,利用聚合酶链反应(polymerase chain reaction,PCR)技术分析了ICAM-1基因K469E和MCP-1基因-2518A/G多态性。结果:K469E(EE)基因型和-2518A/G(GG)基因型频率在Ⅰ期组、Ⅱ期组、Ⅲ期组、Ⅳ期组与0期对照组之间有显著差异(P0.01)。K469E(EE)基因型者胃癌侵袭与转移的风险显著增加。-2518A/G(GG)基因型者胃癌侵袭与转移的风险也显著增加。基因突变的协同分析发现K469E(EE)/-2518A/G(GG)基因型者在Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期与0期对照组中的分布频率经χ2检验有显著差异(P0.01)。K469E(EE)/-2518A/G(GG)基因型者胃癌侵袭与转移的风险显著增加。K469E(EE)和-2518A/G(GG)基因型之间存在超相乘模型的交互作用。结论:K469E(EE)和-2518A/G(GG)基因型均是胃癌侵袭与转移的易患因素,基因多态性的交互作用增加了胃癌侵袭与转移风险。     

狼疮肾炎患者PBMC-CM对系膜细胞表达MCP-1的影响

目的探讨狼疮肾炎（心）患者外周血单个核细胞条件培养液（PBMC-CM）对系膜细胞表达单核细胞趋化蛋白-1（MCP-1）的影响。方法用免疫组化观察LN患者PBMC-CM对系膜细胞表达MCP-1和蛋白激酶C（PKC）的影响。结果LN患者PBMC-CM干预系膜细胞后,系膜细胞增多,培养上清Ⅳ型胶原和层黏蛋白表达增加,系膜细胞MCP-1、PKC表达增加,呈直线相关关系。结论LN患者PBMC-CM能刺激系膜细胞增殖,促进细胞外基质增多及MCP-1的表达增加,从而可能参与LN发病。     

氯沙坦对动脉粥样硬化兔的MCP-1及基因表达的实验研究

为了探讨血管紧张素Ⅱ的Ⅰ型受体(AT1R)拮抗剂氯沙坦(Losartan)的抗动脉粥样硬化(AS)作用及观察其是否能抑制单核细胞趋化蛋白-1(MCP-1)的蛋白及基因表达,我们通过高脂饮食及内皮损伤术建立兔AS模型,一组用Losartan(25mg/kg/d),另一组不用,喂养4个月,观察血管内膜的变化;同时做免疫组化及原位杂交,分别观察MCP-1蛋白及基因的表达。结果发现Losartan治疗组兔主动脉内膜面积及内、中膜面积之比均小于未治疗组,其MCP-1的蛋白及mRNA的表达亦明显减少,表明Losartan可通过抑制MCP-1的产生而具有抗AS作用。     

SLE患者检测hsCRP的临床意义

目的探讨系统性红斑狼疮(SLE)患者超敏C反应蛋白(hsCRP)与病情及补体间的关系。方法对115例系统性红斑狼疮的患者,采用系统性红斑狼疮疾病活动指数(SLEDAI)评估狼疮病情。采用比浊法检测超敏C反应蛋白和补体水平。结果 115例患者中有42例(36.5%)超敏C反应蛋白升高,超敏C反应蛋白增高与感染相关(P0.001),伴有细菌、病毒、寄生虫感染的患者超敏C反应蛋白增高。狼疮性肾炎组超敏C反应蛋白(29.21±3.82)mg/L较非狼疮性肾炎组(27.23±2.46)mg/L轻度增高,但结果无统计学意义。超敏C反应蛋白增高组的患者较正常组患者,补提水平显著减低(P=0.03)。结论超敏C反应蛋白增高与系统性红斑狼疮患者合并感染及低补体血症相关。超敏C反应蛋白可以作为评估狼疮患者是否合并感染的有效指标。     

MCP-1在胚胎种植中的作用

趋化因子是一类对中性粒细胞、单核细胞、嗜碱性粒细胞等起趋化和激活作用的多功能糖蛋白,介导炎症和免疫反应,单核细胞趋化蛋白-1（MCP-1）属于CC类趋化因子家族的一员。近年来研究表明,在激素的调节作用下,MCP-1在胚胎种植中发挥重要作用,其机制主要为趋化并激活单核巨噬细胞,参与Th2型免疫偏移及促进血管生成。     

云南汉族系统性红斑狼疮与HLA-DRB1、DQA1、 DQB1相关性研究

系统性红斑狼疮 (systemic lupus erythem atosus,SL E)发病机理极为复杂。由于 HL A- 类抗原在免疫应答及调节中的重要作用 ,近年来 HL A基因多态性与疾病相关性一直是研究的热点。有研究显示 HL A- DR、DQ基因位点与 SL E的发病及某些类型自身抗体的形成密切相关 [1 ] 。我们采用 PCR-序列特异性引物 (sequence specific primer,SSP)技术进行 HL A-DRB1、DQA1、DQB1基因分型 ,研究云南汉族 SL E与以上等位基因的相关性 ,为进一步探讨 SL E发病机理提供重要的遗传学依据。1　对象与方法1.1　研究对象　病例组为云南籍汉…     

广西瑶族与汉族人群TGF-β1基因启动子-509 C/T多态性的研究

目的研究TGF-β1(转化生长因子-β1)基因多态性在广西瑶族与汉族人群中的分布.方法应用聚合酶链反应-限制性片段长度多态性技术检测150名瑶族人和190名汉族人的TGF-β1基因多态性,比较两组人群TGF-β1基因型和等位基因的分布频率.结果在瑶族人中CC基因型占46.0%、CT基因型占43.3%、TT基因型占10.7%;在汉族人中CC基因型占30.0%、CT基因型占51.1%、TT基因型占19.9%.两组人群TGF-β1基因型的分布频率差异有显著性(P＜0.05).结论瑶族与汉族人群TGF-β1基因多态性分布频率差异有显著性.     

MCP-1 promoter polymorphism in Spanish patients with systemic lupus erythematosus

The possible role of the functional polymorphism located in the regulatory region of the monocyte chemoattractant protein-1 (MCP-1) gene in the susceptibility to systemic lupus erythematosus (SLE) was investigated. Two hundred and seventy-six SLE patients (among them, 99 with lupus nephritis and 55 with cutaneous vasculitis) and 194 ethnically matched healthy controls were included in the study. Genotyping for -2518 (A/G) MCP-1 gene polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No association between -2518 (A/G) MCP-1 polymorphism and susceptibility to SLE nor to lupus nephritis was found. However, a significant increase in the frequency of genotype AG and a decrease in the frequency of genotype AA were found among patients with cutaneous vasculitis (51% of AG vs. 32% in individuals without cutaneous vasculitis; P=0.008, OR=2.2, 95% CI: 1.18-4.25; and 47% of AA vs. 64%; P=0.03, OR=0.5, 95% CI: 0.27-0.96, respectively). These results indicate an association between the presence of G at position -2518 in the MCP-1 promoter region and the presence of cutaneous vasculitis among patients with SLE. This polymorphism does not seem to influence the susceptibility to SLE nor the appearance of lupus nephritis. Further studies are necessary in order to elucidate the role of this polymorphism in the pathogenesis of other inflammatory autoimmune diseases.     

干扰素调节因子5基因rs2004640多态性与系统性红斑狼疮遗传易感性的荟萃分析

目的:系统评价干扰素调节因子5基因(IRF5)rs2004640单核苷酸多态性与系统性红斑狼疮的遗传易感性在不同种族的相关关系。方法:检索Pubmed数据库、万方数据库、CNKI数据库发表的有关IRF5 rs2004640单核苷酸多态性与SLE病例对照研究的文献,应用review manager5软件,采用Mantel-Haenszel-Peto法荟萃分析IRF5 rs2004640单核苷酸多态性在不同种族中的研究。结果:荟萃分析包括亚洲、欧洲-美洲高加索人群、墨西哥印欧混血、美国黑人等不同人群的IRF5 rs2004640单核苷酸多态性14个研究,共11 725例样本。亚洲人群IRF5 rs2004640 T等位基因频率26.3%~45.5%,高加索人群IRF5rs2004640 T等位基因频率44%~56%。分别荟萃分析亚洲和高加索人群与该多态性位点关联,均提示这两种人群IRF5rs2004640 T等位基因与狼疮发病密切相关(亚洲人群OR值1.35,95%CI 1.22~1.50;高加索人群OR值1.42,95%CI 1.32~1.54;P<10-6)。荟萃分析总的结果表明IRF5 rs2004640 T等位基因与狼疮发病密切相关(OR=1.42,P<10-6)。结论:IRF5rs2004640基因多态性在不同种族人群中的荟萃分析肯定了IRF5 rs2004640 T等位基因和系统性红斑狼疮发病相关。     

No association of the MCP-1 promoter A-2518G polymorphism with bipolar disorder in the Korean population

It has been suggested that bipolar disorder is associated with altered immune function. Monocyte chemoattractant protien-1 (MCP-1) is a chemokine that influences both neural and immune functions. We thus hypothesized that MCP-1 may be related to the development or pathophysiology of bipolar disorder. In this case–control study, we investigated the association between the A-2518G single nucleotide polymorphism (SNP) of the MCP-1 promoter and bipolar disorder. Patients with bipolar disorder (n = 183; bipolar I = 145, bipolar II = 38) and healthy controls (350) were recruited for the study. No significant allelic or genotypic association was detected between the A-2518G polymorphism and any sample of bipolar disorder patients. When we pooled the healthy controls and the cases of bipolar I disorder from previous Korean studies and this study, we again found no significant association. No significant difference in either allele frequency or genotype distribution was observed between bipolar I and bipolar II disorders. There was no difference in the age at onset of bipolar disorder among the three genotype groups. Our data suggest that the A-2518G polymorphism of MCP-1 is not a major susceptibility factor for bipolar disorder in the Korean population. However, the physiological role of MCP-1 is highly suggestive of its being associated with bipolar disorder, and further analyses of other SNPs of MCP-1 remain to be performed.     

血清抗C1q抗体在系统性红斑狼疮疾病活动性判断及狼疮肾炎诊断中的价值

目的探讨抗C1q抗体(C1qAb)在系统性红斑狼疮(SLE)活动性及狼疮肾炎(LN)诊断和疾病活动性判断中的价值。方法采用酶联免疫吸附法检测SLE患者(n=89)、疾病对照组(n=56)和正常对照组(n=42)血清中的抗C1q抗体阳性率,并与SLE患者临床实验室指标﹑活动性评分进行分析。结果 C1qAb的阳性率在SLE患者中显著高于疾病对照组和正常对照组患者(P<0.05);C1qAb阳性的SLE患者肾损发生率、活动性狼疮发生率及抗dsDNA抗体的阳性率均高于C1qAb阴性患者(P<0.05);C1qAb与SLEDAI活动性评分、抗核小体抗体(anti-nucleosome antibody,AnuA)及抗dsDNA抗体呈正相关(P<0.05)。结论抗C1q抗体对SLE的诊断和疾病活动性判断有重要价值;抗C1q抗体参与了SLE肾脏损害的发病机制。     

A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus

Nowadays, most of the young women affected by Systemic Lupus Erythematosus (SLE) can carry out one or more pregnancies thanks to the improvement in treatment and the consequent reduction in morbidity and mortality. Pregnancy outcome in these women has also greatly improved in the last decades. A correct timing for pregnancy (tailored on disease activity and established during a preconception counselling), together with a tight monitoring during the three trimesters and the post-partum period (to timely identify and treat possible obstetric complications or maternal disease flares), as well as the concept of multidisciplinary management, are currently milestones of the management of pregnancy in SLE patients. Nevertheless, the increasing knowledge on the compatibility of drugs with pregnancy has allowed a better treatment of these patients, by choosing medications that control maternal disease activity without harming the foetus. However, particular attention and strict monitoring should be dedicated to SLE pregnant women in particular clinical settings: patients with lupus nephritis and patients with aPL positivity or Antiphospholipid syndrome, who are at higher risk for maternal and foetal complications, but also patients with anti-Ro/SSA and/or anti-La/SSB antibodies, because of the risk of neonatal lupus. A discussion on family planning, as well as counselling on contraception, should be part of the everyday-practice for physicians caring for SLE women during their reproductive age. Another issue is the possible reduction of fertility in these women, that can be due to different reasons. Consequently, the request for assisted reproduction techniques has been increasing in the last years, so that rheumatologists and gynaecologists should be prepared to counsel SLE patients also in this particular setting.     

Ets-1在系统性红斑狼疮中的研究进展

系统性红斑狼疮(SCE)是一种典型的系统性自身免疫性疾病,其发病机制尚未明确,其中T、B细胞功能异常起着重要作用.转录因子Ets-1作为SLE的易感基因之一在淋巴细胞分化与细胞因子调节上起重要作用.Ets-1除影响B细胞分化和功能外,对T细胞的生存、增殖、发育和功能起重要作用.虽然Ets-1在SLE发病中的确切机制仍尚未明确,但越来越多的研究表明Ets-1在SLE的发生发展中起着重要作用.     

Association study of interleukin-19 rs2243188 polymorphism with systemic lupus erythematosus in a Chinese population

Abstract

The purpose of this study was to evaluate whether a single-nucleotide polymorphism (SNP), rs2243188 of interleukin-19 (IL-19), show significant evidence for association with SLE in a Chinese population. A total of 545 SLE patients and 613 healthy controls were collected in the present study. The genotyping of IL-19 rs2243188 polymorphism was detected by TaqMan allele discrimination assay on the 7300 real time polymorphism chain reaction system. The minor C allele of rs2243188, relative to the major A allele, appeared to have a significantly lower frequency in SLE patients (31.0%) as compared with controls (35.5%) (χ²?=?5.19, p?=?0.023). We also discovered a statistical significance in the dominant model (CC?+?CA versus AA: OR?=?0.755, 95% CI?=?0.598–0.953, p?=?0.018). However, no significant difference in genotype distribution was found between SLE patients and controls (p?=?0.056). Furthermore, an increased frequency of CC genotype were also detected in lupus nephritis (LN) groups as compared with non-LN groups (p?=?0.024). Besides, the individuals with CC genotype had a 2.201-fold higher risk for the susceptibility to LN than those A allele carriers (AA?+?CA) (p?=?0.006). Unfortunately, the analyses on the relationship of IL-19 rs2243188 with several clinical manifestations of SLE failed to find any significant results. In conclusion, our observations suggested the minor C allele of SNP rs2243188 might be a protective factor for SLE in a Chinese Han population. Moreover, the subgroup analysis highlighted that IL-19 rs2243188 SNP was associated with the susceptibility to LN patients.     

MCP-1, RANTES, and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus

Chemokines and cytokines play an important role in the inflammatory development and progression of autoimmune diseases. The aim of the present study was to evaluate the role of MCP-1, SDF-1, and RANTES polymorphisms as susceptibility markers for systemic lupus erythematosus (SLE) in a group of Mexican patients. MCP-1-2518, SDF-1 G801A, and RANTES-28 polymorphisms were determined in 242 patients with SLE and 220 ethnically matched healthy controls by the polymerase chain reaction–restriction fragment length polymorphism technique. The differences between patients and healthy controls were evaluated by χ², Fisher’s exact test, and Woolf method for odds ratio. A moderately increased frequency of MCP-1-2518 A allele (p = 0.033, pC = NS) and AA genotype (p = 0.017, pC = NS) existed in SLE patients compared with healthy controls. There was a relationship between polymorphisms and some clinical and laboratory characteristics. SLE patients with and without antiphospholipid syndrome demonstrated different distribution of SDF-1 G801A genotype frequencies. On the other hand, patients with leukopenia, anti-dsDNA, and antiphospholipid autoantibodies demonstrated different MCP-1-2518 genotype distribution compared with patients without these features. Our results suggest that MCP-1 polymorphism is moderately associated with the genetic susceptibility to SLE in Mexican individuals. The polymorphisms could be related to specific clinical and laboratory characteristics in these patients.     

Urinary TWEAK and the activity of lupus nephritis

The TNF superfamily cytokine TWEAK induces mesangial cells, podocytes, and endothelial cells to secrete pro-inflammatory chemokines including MCP-1, IP-10 and RANTES, which are crucial in the pathogenesis of lupus nephritis (LN). As TWEAK regulates the secretion of these inflammatory mediators, we studied whether urinary TWEAK (uTWEAK) levels might be predictive and/or diagnostic in LN. In a cross-sectional study of a large, multi-center cohort of systemic lupus erythematosus (SLE) patients, uTWEAK levels were higher in patients with active as compared to never or non-active nephritis (median (IQR): 16.3 (9.9-23.0) versus 5.5 (2.3-16.8) pg/mg creatinine, p=0.001), and levels of uTWEAK correlated with the renal SLE disease activity index (rSLEDAI) score (r=0.405, p<0.001). uTWEAK levels were higher in patients undergoing a flare as compared to patients with chronic stable disease (11.1 (8.1-18.2) and 5.2 (2.3-15.3) pg/mg creatinine, respectively; p=0.036). Moreover, uTWEAK levels were significantly higher in patients undergoing a renal flare, as opposed to a non-renal flare (12.4 (9.1-18.2) and 5.2 (3.0-11.9) pg/mg creatinine, respectively; p=0.029). An accurate, non-invasive method to repeatedly assess kidney disease in lupus would be very helpful in managing these often challenging patients. Our study indicates that urinary TWEAK levels may be useful as a novel biomarker in LN.