Toll样受体与系统性红斑狼疮和动脉粥样硬化

目前,越来越多的研究表明Toll样受体信号通路在系统性红斑狼疮(SLE)和动脉粥样硬化(AS)等疾病的发病中发挥着重要作用。同时,SLE患者早发动脉粥样硬化发病率显著增高,提示两者的发病存在相关性。SLE多见于年轻女性,其发生心血管事件的概率高达同年龄组正常人群的50倍。     

Toll样受体基因多态性与牙周炎相关性研究进展

牙周炎是一种多基因复杂疾病,尽管牙菌斑是该病的始动因子,但不同个体对于菌斑微生物的反应程度不同,因而不同个体对牙周炎的易感性也有所差异。Toll样受体（TLR）是一种重要的模式识别受体,在宿主对病原微生物的免疫反应当中起着重要的作用。近年来有很多关于TLR基因多态性与牙周炎的研究,但其结果存在人群和种族差异。     

Toll样受体-9的研究进展

Toll样受体-9(Toll-like receptor 9,TLR9)是哺乳动物TLRs家族中一员,作为细胞表面的天然模式识别受体,主要参与免疫刺激序列(CpG序列)激活免疫细胞的信号传导,从而在天然抗感染免疫及联系天然免疫和获得性免疫中发挥重要作用。通过对TLR9-CpG作用通路的研究,将促进天然免疫机制研究的进一步深入,有利于解决诸如:CpG佐剂、DNA疫苗、CpG抗感染、抑制肿瘤、预防过敏反应等实际应用过程中存在的问题。     

Toll样受体与树突状细胞

Toll样受体(TLR)在介导固有免疫和适应性免疫应答中有重要作用,可以表达于多种免疫细胞,包括树突状细胞(DC).了解Toll样受体的免疫学基础、与DC之间的联系以及其在免疫耐受干预方面的作用很有必要.     

Toll样受体在适应性免疫中的作用与相关机制研究进展

TLRs是一类模式识别受体，能够被微生物的特异性成分和某些宿主分子所激活，在固有免疫系统中起着决定性的作用。同时大部分病原体通过TLPs激活抗原提呈细胞(主要是树突状细胞)上调其MHC分子表达，启动CD4^ T细胞向Th1型细胞分化。而当机体遭遇多细胞寄生虫感染或接触变应原时，CD4^ T细胞则向1112型细胞分化，这一类免疫反应可能是通过一系列不同于TLRs的固有识别系统进行调控，但究竟是通过目前未知的PRRs还是通过缺失自身标记的机制对病原体进行识别目前还不明了。进一步了解TLRs调节适应性免疫的过程不但能够发展治疗感染性疾病的新途径，而且可能为变态反应和某些自身免疫疾病发病机理深入研究以及治疗和防治提供新方法。     

Toll样受体与树突状细胞

树突状细胞是目前已知的功能最强的抗原递呈细胞 ,可通过表达的Toll样受体 (TLR )来识别病原微生物特有的保守成分 ,如脂多糖、细菌DNA中非甲基化的CpG序列和病毒的dsRNA等 ,并通过TLR介导的信号传导通路激活转录因子NF κB和Jun/Fos,引起炎性细胞因子的释放和促进树突状细胞成熟 ,并且可以影响免疫应答的类型。为制备树突状细胞疫苗提供了一条新思路     

Toll样受体在适应性免疫中的作用与相关机制研究进展

TLRs是一类模式识别受体 ,能够被微生物的特异性成分和某些宿主分子所激活 ,在固有免疫系统中起着决定性的作用。同时大部分病原体通过TLRs激活抗原提呈细胞 (主要是树突状细胞 )上调其MHC分子表达 ,启动CD4 + T细胞向Th1型细胞分化。而当机体遭遇多细胞寄生虫感染或接触变应原时 ,CD4 + T细胞则向Th2型细胞分化 ,这一类免疫反应可能是通过一系列不同于TLRs的固有识别系统进行调控 ,但究竟是通过目前未知的PRRs还是通过缺失自身标记的机制对病原体进行识别目前还不明了。进一步了解TLRs调节适应性免疫的过程不但能够发展治疗感染性疾病的新途径 ,而且可能为变态反应和某些自身免疫疾病发病机理深入研究以及治疗和防治提供新方法。     

Toll样受体4多态性与强直性脊柱炎易感性的荟萃分析

目的 用荟萃分析方法评价toll样受体(TLR)4基因多态性与强直性脊柱炎的关系. 方法 检索在2007年2月前在PubMed及中国期刊全文数据库发表的中英文献.用RevMan 4.2对纳入文献进行荟萃分析,评价合并效应量、功效、异质性及发表偏倚. 结果 共纳入4篇有关Asp299Gly多态位点和3篇Thr399Ile多态位点的病例对照研究.未发现异质性及发表偏倚,合并后功效在80%左右.Asp299Gly位点合并效应量OR=0.94(95%CI:0.66～1.35),Thr399Ile位点合并效应量OR=1.08(95%CI:0.70～1.65). 结论 TLR4基因不是强直性脊柱炎的主要易感基因.     

Toll样受体9与自身免疫性疾病

Toll样受体9(TLR9)可识别细菌和病毒DNA中未甲基化的胞嘧啶-磷酸-鸟嘌呤(CpG DNA)序列,激活固有免疫应答和适应性免疫应答,促进宿主抵抗感染性疾病.近年的研究显示,TLR9活化在自身免疫性疾病发生发展中起重要作用,干预或操控TLR9介导的免疫反应有望成为治疗自身免疫性疾病的新策略.     

Toll 样受体7及Ⅰ型干扰素通路在系统性红斑狼疮中的作用研究

探讨Toll样受体7(TLR7)及Ⅰ型干扰素(IFN-α)通路在系统性红斑狼疮(SLE)发病中的作用.采用实时荧光定量PCR方法检测42例SLE患者和34例正常人外周血TLR7mRNA以及4个干扰素调节基因mRNA的表达水平,同时观察TLR7mRNA的表达量与SLE疾病活动相关指标和干扰素积分(IFN score)的关系.结果,SLE患者外周血TLR7mRNA的表达水平显著增高;TLR7mRNA的表达水平与SLEDAI积分,肾脏损伤指数、抗双链DNA(dsDNA)抗体、抗RNA相关抗体水平及干扰素积分呈正相关;与补体C3、C4、白细胞数呈负相关.TLR7-IFN-α通路可能参与了SLE的病理过程.     

Contribution of Toll-Like Receptor 9 Gene Single-Nucleotide Polymorphism to Systemic Lupus Erythematosus in Egyptian Patients

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease, with multiple genetic and environmental factors involved in its etiology. The toll-like receptor 9 (TLR9) gene has been reported to have important roles in the development and progression of SLE. In this case-control study, the effect of TLR9 polymorphism on susceptibility to SLE was investigated in Egyptian patients.

Methods: We studied the distribution of the TLR9 rs352139 (G + 1174A) single nucleotide polymorphism (SNP) by allele-specific polymerase chain reaction (PCR) in 104 Egyptian patients with SLE and 108 age-, sex-, and ethnically matched controls.

Results: There was no statistically significant difference in the distribution of the AA genotype and alleles between SLE patients and the control group in our study; however, the GA heterozygous patients were three times more likely to develop SLE (P < 0.001). A significant association was detected between TLR9 genotypes and some of the disease manifestations as myositis (p = 0.032), psychosis (p = 0.014), photosensitivity (p = 0.002), and pleurisy (p = <0.001). Moreover, we observed a significant association between the TLR9 AA and GA genotypes and the presence of antinuclear antibodies (ANA) (p = 0.038).

Conclusion: The G + 1174A SNP in the toll receptor 9 gene may contribute to the genetic susceptibility of SLE in Egyptian patients. Also, an influence for this polymorphism on disease manifestations has been elucidated.     

HLA-DQ多态性基因与系统性红斑狼疮易感性

采用PCR-SSO方法对江苏籍汉族SLE患者和正常对照组HLA-DQ作基因分型.结果显示,患者组中DQA1*0102频率(RR=3.43.Pc=0.03164)及HLA-DQA1*0102,DQB1*0601和HLA-DQA1*0102,DQB1*0602单倍型频率(RR=9.4,P=0.027和RR=12.4.P=0.007)均明显高于正常对照组.相反,DQA1*0601频率则显著低于正常对照组(RR=0.29,Pc=0.0461).但没发现任何DQB1等位基因与SLE有关.这提示在汉族SLE与HLA-DQ基因的相关性方面,DQA1*0102起主导作用.DQA1*0102或某个与其紧密连锁的其它基因可能是汉族SLE的易感基因,而DQA1*0601则可能对SLE的发病有一定的保护性.     

SLE患者检测血清ANCA的临床价值

目的 探讨抗中性粒细胞胞浆抗体（ANCA）在系统性红斑狼疮（SLE）患者中检测的临床意义.方法 通过间接免疫荧光法（IIF）检测57例SLE患者血清中的ANCA,对ANCA阳性血清采用免疫斑点法检测抗髓过氧化物酶（MPO）和蛋白酶3（PR3）抗体;同时以35例正常健康者作为对照组.回顾性分析SLE临床表现和实验室检查结果,SLE患者以SLE disease activity index（SLEDAI）分组（SLEDAI≥10为疾病活动组、〈10为疾病非活动组）,分析ANCA与其的相关性.结果 SLE患者中ANCA 阳性率为22.8%,其中核周型（pANCA）阳性12例,阳性率为 21.1%,胞浆型（cANCA）1例,阳性率为 1.7%,靶抗原均为非MPO、PR3;ANCA阳性组与ANCA阴性组SLE活动性存在显著性差异（P〈0.05）,ANCA阳性组患者的补体C3的下降、血沉（ESR）的增高、抗dsDNA抗体的阳性以及皮肤血管炎和肾脏损伤与ANCA阴性组比较,差异有统计学意义（P〈0.05）.结论 ANCA在SLE中有一定阳性检出率,对疾病活动性判断有一定的临床价值.     

凝血指标在系统性红斑狼疮疾病中的临床应用

目的:检测系统性红斑狼疮(SLE)患者外周血中凝血指标及其相关指标来评价临床意义。方法:选用46例SLE患者为观察组,其中活动组26例,非活动组20例;40例正常人为对照组。测定血浆凝血酶原时间(PT),活化部分凝血活酶时间(APTT),血浆纤维蛋白原(FIB)和凝血酶时间(TT),血浆D-二聚体(D-Dimer,D-D)和纤维蛋白(原)降解产物(FDP),血浆抗凝血酶活性(AT:A);其他实验相关指标C反应蛋白(CRP),血沉(ESR)。结果:SLE组D-D及FDP明显高于对照组,PT及APTT比对照组明显缩短(均P<0.01),其他各指标均无统计学意义;SLE活动组ESR、CRP、D-D明显高于非活动组(均P<0.01),而FDP差别无统计学意义。结论:D-D及凝血指标能及时反映SLE患者体内凝血和纤溶系统失衡情况,对于SLE病程发展和控制有其重要的临床指导价值。     

系统性红斑狼疮与遗传性补体缺陷相关性探讨

本文报道了二例经实验证实为补体 C_4缺陷的系统性红斑狼疮患者,长期追踪观察的结果表明,二例患者持续血清 C_4低水平,一例伴有 C_(3)缺陷的患者反复肺部感染.本文并对补体与系统性红斑狼疮间的相互关系进行了简要分析.     

系统性红斑狼疮患者心理干预的研究

目的调查系统性红斑狼疮（SLE）患者心理干预前后的心理状况.方法 67例SLE患者分别于心理干预前后填写症状自评量表（SCL-90）及自制的SLE患者心理影响因素调查表.结果 SLE患者心理千预前与中国常模比较,SCL-90阳性项目数、阳性均分及各种因子均高于中国常模.躯体化、强迫、人际关系、抑郁、焦虑、恐怖、精神病性7种因子与中国常模相比,有非常显著性差异;敌对、偏执与中国常模相比,有显著性差异.而干预后再次测评结果显示：SCL-90各项评分均有下降,干预前后两组相比,总均分,阳性项目数,躯体化、强迫、抑郁、焦虑、恐怖7项有显著性差异,睡眠及饮食情况也明显改善.提示心理干预对改善患者紧张、焦虑、忧郁等不良情绪有明显疗效.结论 SLE患者心理健康状况普遍较差,而心理干预后,可明显改善患者的心理状况,提高患者的生活质量.     

The Tie2 Receptor Antagonist Angiopoietin-2 in Systemic Lupus Erythematosus: Its Correlation with Various Disease Activity Parameters

Background: Systemic lupus erythematosus is one of the autoimmune diseases characterized by multisystem involvement associated with autoantibody and immune complex vasculitis along with endothelial cell damage. Objective: to study the possible role of Angiopoietin- 2 (Ang-2) as a recently highlighted inflammatory and angiogenic mediator in the pathogenesis of SLE and its correlation with the state of another inflammatory marker, P-Selectin, as well as with various markers of the disease activity. Patients and methods: The present study included 3 main groups: active SLE patients (group I), inactive SLE patients (group II) and healthy normal control subjects (group III). Groups I and II were subjected to disease activity assessment using the SLEDAI scoring system and measurement of plasma Ang-2 and P-Selectin by ELISA in addition to various laboratory investigations to assess disease activity as: Complete blood count, ESR, serum creatinine, C3, C4 and 24-h urinary proteins. Results: The mean level of Plasma Ang-2 and P-selectin showed a high significant increase in active group compared to inactive SLE patients and control subjects (p < 0.001).There was a significant positive correlation between Ang-2, P-Selectin, and each of SLEDAI score and 24-h urinary proteins in all SLE patients as well as in the active group, and Ang-2 was a significant independent marker for proteinuria. A significant negative correlation was found between Ang-2, P-Selectin and each of C3, C4. Ang-2 and P-Selectin showed a high sensitivity and specificity in the patients with SLE. Conclusion: Our study suggests that Ang-2 may be a more useful marker than P-Selectin, C3 and C4 in the assessment of disease activity.     

Anti-neutrophil Cytoplasmic Antibodies in New-onset Systemic Lupus Erythematosus and Lupus Nephritis

This study aims to investigate the role of Antineutrophil cytoplasmic antibodies (ANCA) in patients with new-onset systemic lupus erythematosus (SLE). Sixty SLE patients, 28 of whom had lupus nephritis (LN), and 60 normal controls were enrolled; Serum ANCA was measured by enzyme linked immunosorbent assay (ELISA). The clinical and laboratory parameters of the patients were also recorded. Results show that twenty SLE patients were seropositive for ANCA, which was significantly higher than in normal controls. LN patients had significantly higher positive rate of ANCA than patients without nephritis. Compared with ANCA-negative patients, the ANCA-positive patients had significantly higher incidence of nerves system disorder, myocarditis, renal involvement and serositis. The positive rate of gamma-globulin, anti-dsDNA and anti-Sm antibodies were significantly higher in ANCA-positive patients. Elevated IgG and ESR, decreased serum C3/C4 appeared more often in ANCA-positive patients. In addition, serum ANCA level correlated positively with disease activity. Taken together, ANCA might be used as a potential complementary parameter to differentiate LN from SLE without nephritis. In addition, ANCA may serve as a useful marker of the disease activity of SLE.     

系统性红斑狼疮患者自身抗体检测及意义

目的：探讨自身抗体在系统性红斑狼疮（SLE）中的意义。方法：采用放射免疫分析检测50例SLE患者血清中的抗双链DNA（dsDNA）抗体,采用德国IMTEC公司抗核抗体谱线性印迹法检测抗核小体抗体（AnuA）、抗组蛋白抗体（AHA）、抗StuD1等其他自身抗体。结果：抗StuD1阳性率最高（82％）,其次是抗R060KD抗体（80％）和AunA（72％）;抗dsDNA、AHA、抗U1-RNP、抗R052KD、抗SSB的阳性率分别为44％、32％、58％、48％、24％。其他三种自身抗体阳性率很低。结论：SLE患者血清中可出现大量的自身抗体,同时检测多种自身抗体能提高对SLE的鉴别诊断。     

FAS mRNA editing in Human Systemic Lupus Erythematosus

FAS/FASL system plays a central role in maintaining peripheral immune tolerance. Human Systematic Lupus Erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by expansion of autoreactive lymphocytes. It remains unclear whether a defective FAS/FASL system is involved in the pathogenesis of SLE. In this study, we have discovered a novel nucleotide insertion in FAS mRNA. We demonstrate that this novel FAS mutation occurs at mRNA levels, likely through a site-specific mRNA editing process. The mRNA editing mutation is unique for human FAS because the similar mRNA editing event is absent in other human TNF receptor (TNFR) family genes with death domains (DR5, DR6, and TNFR1) and in murine FAS. The adenine insertion mutation in the coding region message causes the alteration of human FAS mRNA reading frame. Functionally, cells expressing the edited FAS (edFAS) were refractory to FAS-mediated apoptosis. Surprisingly, cells from SLE patients produced significantly more edFAS products compared to cells from normal healthy controls. Additionally, we demonstrated that persistent engagement of T-cell receptor increases human FAS mRNA editing in human T cells. Our data suggest that the site-specific FAS mRNA editing mutation may play a critical role in human immune responses and in the pathogenesis of human chronic inflammatory diseases.