神经精神性狼疮患者免疫学的指标分析

目的：探讨对神经精神性狼疮的发生和早期诊断有意义的免疫学指标。方法：对伴发神经精神性症状和不伴有神经精神性症状的104例红斑狼疮患者C3、C4、IgG、IgA、IgM、抗核抗体（Antinuclear antibody，ANA）、抗核糖体P蛋白（Anti-ribosome P antibody，ARPA）、抗核糖核酸蛋白抗体（Nuclear ribonuclear protein antibody，anti-NRNP）、抗脑神经抗体（Anti-brainantibody，ABA）及抗双链DNA（anti-dsDNA）进行回顾性分析，并在NPLE组将患者按有无合并精神症状进行分组，考查精神症状与上述部分指标的关联。SPSS12.0进行数据处理。结果：ABA阳性例数在NPLE组（62例中51例阳性）分布明显高于非NPLE组（42例中12例阳性），在合并精神症状的NPLE组比无精神症状组比例高（χ^2=4.885，P=0.027），其余各项指标组间比较均无显著性差异。结论：C3、C4水平的降低，IgG、IgA、IgM升高及ANA、APRA、anti-NRNP、anti-dsDNA阳性变化不具有NPLE诊断和预测特异性，是SLE免疫损伤的共有表现；ABA对NPLE的发生及NPLE伴发的精神症状的出现有重要作用。     

系统性红斑狼疮患者个性的艾森克量表评定

本文采用 EPQ 对45名 SLE 患者和45名正常对照者进行1∶1配比病例对照研究,结果表明,内倾个性的人发生 SLE 的机遇高于无内倾个性的人3.16倍;具有不稳定型个性的人发生 SLE 的机遇高于稳定个性的人3.40倍。     

系统性红斑狼疮病人血T,B淋巴细胞Bcl—2的表达

目的：探讨Ｂｃｌ－２在系统性红斑狼疮（ＳＬＥ）发病机制中作用。方法：采用流式细胞仪双标记法检测３１例ＳＬＥ病人外周血Ｔ、Ｂ细胞Ｂｃｌ－２蛋白表达。结果：发现活动期ＳＬＥ病人活动期ＳＬＤ病人ＣＤ３＾＋、ＣＤ４＾＋和ＣＤ８＾＋Ｔ细胞Ｂｃｌ－２蛋白表达明显高于非活动期ＳＬＥ病人、其他疾病组和正常对照组。ＣＤ１９＾＋Ｂ细胞Ｂｃｌ－２蛋白表达在各组之间并无统计学差异。ＣＤ３＾＋Ｔ细胞Ｂｃｌ－２蛋白表达的平均     

Spontaneous production of bone-resorbing lymphokines by B cells in patients with systemic lupus erythematosus

The culture supernatant of B cells from patients with active systemic lupus erythematosus (SLE) who had never been treated with corticosteroids had bone-resorbing activity (BRA) which stimulated the⁴⁵Ca release from prelabeled murine fetal bones. Then we studied the characteristics and the relationship of this BRA with several lymphokines previously reported. The BRA was eluted as three peaks at approximately 17,000, 35,000, and 80,000 daltons by Sephacryl S-200 column chromatography. Recombinant (r)IL 1, rIL 1, and rTNF possessed BRA, but rIL 4 and rIL 6 did not. Furthermore, the BRA from SLE B cells was absorbed with anti-IL 1 antibody but not with anti-IL 1 and anti-TNF antibody. Therefore, the fact that SLE B cells produce BRA which corresponds to IL 1 and IL 1 produced by B cells might be one of the causes of bone destruction in SLE patients.     

雌二醇对系统性红斑狼疮小鼠模型肾组织芳香酶表达的影响

目的：研究雌二醇对系统性红斑狼疮（ Systemic lupus erythematosus, SLE）小鼠模型肾组织芳香酶表达的影响。方法：BALB／c小鼠卵巢切除后采用ConA活化的同系脾细胞诱导SLE，同时给予不同剂量苯甲酸雌二醇，并设立对照组。于4、6、8和10周用ELISA法检测外周血和肾组织雌二醇（Estradiol，E2）水平，RT-PCR检测肾组织芳香酶mRNA的表达。结果：SLE模型小鼠外周血和肾组织E2水平随着外源性给予苯甲酸雌二醇剂量的加大而升高，与未进行SLE模型诱导的小鼠相比较，SLE模型鼠外周血和肾组织E2水平升高（P〈0．05）；正常BALB／c小鼠肾组织芳香酶mRNA低表达；随着SLE炎症的诱导及E2水平的升高，肾组织芳香酶mRNA的表达增加。结论：E2通过促进SLE小鼠模型肾组织芳香酶mRNA的表达影响SLE发生发展。     

Normal mitogen-induced suppression of the interleukin-6 (IL-6) response and its deficiency in systemic lupus erythematosus

A low-frequency suppressor-cell population in normal peripheral blood inhibits the B-cell CESS response to IL-6, following pokeweed mitogen stimulation. The suppression of IL-6 responsiveness is (i) radiation sensitive, (ii) directed against CESS targets and not mediated by inhibition of IL-6 production, and (iii) associated with nonspecific cytotoxic activity against CESS targets. The generation of these cytolytic cells is also radiation sensitive. A correlation was found between PWM-induced cytotoxicity against CESS and the suppression of IL-6-dependent IgG production. But cytotoxicity toward CESS targets is not responsible for this suppression because (i) IL-2 induces equivalent or greater nonspecific cytotoxicity against CESS in the total absence of suppression of CESS-derived IgG production and (ii) suppression is also induced by mitogen-activated PBL separated from CESS targets by a cell-impermeable membrane. This suppression was not mediated by TNF/ or IFN-. In systemic lupus erythematosus, suppression of IL-6-dependent IgG production is impaired in patients with active disease (29.2±13.7%) compared to patients with inactive disease (70±19.5%) or normal controls (82.8±9.2%). There is also a defect in mitogen-induced nonspecific cytotoxicity in active SLE (specific lysis 15.1±3.5%, compared to 34±4% in normals). Pokeweed mitogen-activated PBL can therefore normally induce suppression of B-cell IL-6 responses and this response is deficient in lupus.     

Human cytomegalovirus in patients with systemic lupus erythematosus

The objective of this study was to determine the frequencies of human cytomegalovirus (HCMV) infection and HCMV genome copy number in blood of consecutive (treated from several months to several years) systemic lupus erythematosus (SLE) patients (22 women). The obtained results were compared to the healthy controls (15 women). All patients fulfilled at least four of the 1982 revised American rheumatism association (ARA) classification criteria for SLE. Our patients demonstrated three or four of the nine possible organ systems involved and most of them had mild SLE with SLE disease activity index (SLEDAI) score < 10 at time when blood samples were collected to detect HCMV. Quantitative analysis of HCMV genome was performed with aid of sequence analyzer ABI PRISM ^TM 7700 Perkin Elmer. Primers and probe were constructed on the basis of IE4 region of HCMV genome. The viral load was expressed as log₁₀ of calculated HCMV genome copy number. Qualitative analysis revealed that 100% of our SLE patients were infected with HCMV, whereas in the control group only 73% of persons were HCMV positive. Statistically significant difference was demonstrated when the strength of the association between SLE or controls and infection of HCMV was calculated (estimated by Fisher's exact test, P value = 0.02). Higher viral DNA copy number was observed in whole blood of SLE patients than in the control group (338.45 ± 221.76 and 229.00 ±405.61 copies/ml respectively) but did not reach statistical significance level (95% confidence interval from 170.41 to 249.32, P = 0.71). Furthermore percentage of patients with HCMV-DNA copy number >2.0 × 10² copies/ml was statistically significantly higher than this one in controls. The data show association between HCMV infection and SLE, which should be taken into account during the course of SLE.     

Immunological characterization of small nuclear ribonucleoproteins reactive with sera of patients with systemic lupus erythematosus

We have previously reported the purification of Sm and RNP antigens from goat liver and identified two polypeptides of molecular weights 70 and 80–90 kd as RNP specific and of 14 and 30 kd as Sm specific. In this communication the effect of ribonuclease and trypsin on Sm and RNP antigens was studied at the polypeptide level. We found that the RNP antigenic determinant polypeptides of 70 and 80–90 kd are lost as a result of such treatment, whereas there is no effect on the Sm-specific 14- and 30-kd polypeptides. The role of RNA in the antigenicity of Sm and RNP was studied by dissociation and reconstitution studies. The antigens were fractionated into protein and RNA and the individual fractions were tested for Sm and RNP activity by counterimmunoelectrophoresis (CIE) and enzyme-linked immunosorbent assay (ELISA). The RNA fraction did not react alone with anti-Sm and anti-RNP sera with either of the assays. Conversely when the protein fraction was tested by CIE, only Sm antigenicity was detectable. In the ELISA both Sm and RNP activities were demonstrated in the protein fraction. These results show that the presence of RNA is important in the immunoprecipitation reactions involving only RNP antigen, whereas Sm activity is independent of RNA. In addition, when the reaction is carried out by an assay involving primary antigen-antibody reaction (e.g., ELISA), RNP antibodies react with protein fractions alone, without the presence of RNA. We also report the glycoprotein nature of Sm-specific polypeptides. The antigen was found to react specifically with concanavalin A (Con A), indicating the presence of glycosyl and/or mannosyl residues. The observed glycoprotein nature of the Sm-specific polypeptides possibly explains their remarkable stability, unlike RNP-specific polypeptides, which are susceptible to proteolytic attack.     

New insights into the progression from cutaneous lupus to systemic lupus erythematosus

ABSTRACT

Introduction

Between 5 and 25% of patients with cutaneous lupus erythematosus (CLE) can progress to systemic lupus erythematosus (SLE) during the course of the disease. There is no clear predictive guideline for the progression of CLE to SLE.     

人体T细胞CD_8~+VV~+亚群在活动性SLE患者中显示反抑制活性

反抑制T 细胞(TCS)借助T 辅助细胞对抗T 抑制细胞的抑制效应,参与免疫调节。小鼠和人体的TCS 都表达长绒毛野豌豆凝集素受体(VV—R)。人体TCS 则主要是CD_8~+VV~+T 亚群,和临床多种疾病免疫功能异常密切相关。本文用抗VV 抗体单色和双色免疫荧光法和流式法细胞术(FCM)测知正常人VV~+T 亚群的比例是16.6±2.9%。用FCM 双色免疫荧光法检测到活动期SLE 患者CD_8VV~+亚群百分比高达23.63%和对照组(8.50%)及稳定期(14.49%)相比差异显著。然而CD_4~+VV~+亚群在三组SLE 中基本不变。进一步深入分析是做有关CD_8VV~+T 细胞亚群的功能测定,证实活动性SLE 患者VV~+T 细胞具有比正常个体高得多的反抑制活性,相对反应值从100%提高到485%和625%。提示CD_(?)VV~+细胞和SLE 免疫调节功能紊乱密切相关。     

Monocyte (macrophage)-specific antibodies in patients with systemic lupus erythematosus (SLE)

Antibodies reactive for monocytes (macrophages) were found in the sera of patients with systemic lupus erythematosus (SLE). These antibodies were preseent in both IgG and IgM fractions and worked under both warm (37°C) and cole (4°C) conditions. These antibodies were specific for monocytes, because cytotoxic antibodies for monocytes were absorbed with monocytes, but not with T cells, B cells, and granulocytes. Furthermore, their specificity is also different from anti-HLA-DR antibody. The presence of these antibodies correlated with the activity of disease. They were found in 12 of 14 active SLE and 7 of 16 inactive SLE patients. The treatment of normal monocytes with these SLE sera and complement resulted in the depletion of their accessory function for T-cell activation and their phagocytic activity. In the previous paper, we reported that the accessory function of monocytes for T-cell activation was impaired in SLE patients. These results suggest that monocyte-specific antibodies play an important role in the pathogenesis of SLE through disturbing the monocyte regulatory function for immune responses.     

Reduced function of HLA-DR-positive monocytes in patients with systemic lupus erythematosus (SLE)

Accessory function of monocytes for T-cell activation was studied in patients with systemic lupus erythematosus (SLE). Nylon column-purified T cells alone were not activated to proliferate by stimulation with concanavalin A (Con A), but the addition of dish-adherent monocytes restored the T-cell response in a dose-dependent manner (accessory function). This accessory function is mediated by HLA-DR-positive monocytes. This accessory function of monocytes was markedly impaired in SLE patients. The dysfunction of monocytes was marked in an active stage of SLE but not in an inactive stage of SLE. Furthermore, SLE T cells were not fully activated with Con A in the presence of normal monocytes, suggesting that both monocyte and T-cell functions were impaired in SLE patients. The dysfunction of SLE monocytes was due to neither the development of suppressor monocytes nor the overproduction of prostaglandins, because SLE monocytes did not suppress the accessory function of normal monocytes and indomethacin did not restore the dysfunction of SLE monocytes. The percentage of HLA-DR-positive cells in a monocyte population was markedly decreased in active SLE patients and moderately decreased in inactive SLE patients. Thus, the impairment of accessory function of monocytes in SLE patients seems to be derived from a decrease in HLA-DR-positive monocytes. These results suggest that the dysfunction of HLA-DR-positive monocytes plays an important role in the pathogenesis of SLE.     

Togavirus-like particles in renal epithelium of patients with systemic lupus erythematosus

Summary Virus-like particles, about 45 nm in diameter, were present in renal epithelium (tubules and podocytes) of 12 patients with confirmed systemic lupus erythematosus (SLE) and in 2 patients with probable SLE. They were not detected in renal biopsies from non-SLE patients. Morphologically, they suggest togavirus-like particles.     

系统性红斑狼疮PBMCs c-myc mRNA的表达及其与疾病活动性相关性研究

目的:探讨系统性红斑狼疮(SLE)外周血单个核细胞(PBMCs)的c-myc mRNA表达在SLE发病中的作用.方法:从33例SLE患者及20例健康对照组外周静脉血中分离PBMCs,提取总RNA作模板,按文献设计合成c-myc引物,以β-actin作内参,应用半定量逆转录-聚合酶链反应(RT-PCR)检测SLE患者及健康对照的PBMCs c-myc mRNA表达水平并进行组间比较,用系统性红斑狼疮疾病活动性指数(SLEDAI)评定每例患者疾病活动性,并对SLE患者PBMCs的c-myc mRNA表达水平与SLEDAI进行相关分析.结果:c-myc及β-actin的RT-PCR扩增产物电泳显示分别为268和163 bp条带.SLE患者PBMCs的c-myc mRNA相对表达量为0.58±0.26,而正常对照的相对表达量为0.07 ±0.04,两组差别有显著性(t'=11.024,P=0.000).25例活动期SLE患者的c-myc mRNA相对表达量为0.62±0.25,而8例缓解稳定期SLE患者的c-myc mRNA相对表达量为0.25 ±0.01,组间差别也有显著性(t'=7.86,P=0.000).SLE患者PBMCs的c-myc mRNA相对表达量与SLEDAI呈正相关(r =0.865 1,P＜0.05).结论:SLE患者PBMCs的c-myc mRNA表达异常,c-myc mRNA表达水平与SLE疾病活动评分指数呈直线正相关关系.c-myc mRNA表达水平可作为判断SLE疾病活动性的一个指标.     

人巨细胞病毒pp65对系统性红斑狼疮诱导作用的研究

目的 探究人巨细胞病毒(HCMV) pp65是否可以诱发正常C57BL/6小鼠产生系统性红斑狼疮(SLE)相关实验室诊断指标的变化.方法 构建HCMV pp65原核表达质粒与真核表达质粒,然后进行HCMV pp65原核蛋白表达与纯化.间接法ELISA检测anti-pp65 IgG、dsDNA、抗核抗体(ANA),竞争法ELISA检测血浆中IL-1b、IL-6、TNF-α浓度.结果 成功获得HCMV pp65原核表达蛋白和真核表达质粒,免疫小鼠后血清中anti-pp65、抗dsDNA抗体、ANA、IL-6均有明显上升趋势.结论 HCMVpp65可以使C57BL/6小鼠SLE相关检测指标发生明显改变,这一结果有助于进一步研究自身免疫病的发病机制与影响因素.     

系统性红斑狼疮的分子遗传学研究

系统性红斑狼疮（systemiclupuserythematosus,SLE）是一种复合性多基因的自身免疫性疾病。遗传因素在SLE易感性方面起重要的作用。该文介绍目前已知几个与SLE的易感性有关的遗传基因。通过对这些基因研究,有利于阐明SLE的发病机制,进一步为SLE的预防、诊断和治疗提供重要的依据。     

Vitamin D and systemic lupus erythematosus - The hype and the hope

Over the past 20 years, much has been written about the potential role of vitamin D in on adverse health outcomes. In recent years, evidence has accumulated regarding the effect of vitamin D on the immune system, and its different cells. Some studies have noted lower vitamin D concentrations in patients with SLE. These epidemiological data still not answer the question: is vitamin D deficiency the cause or the effect? To answer this, we will discuss the association between vitamin D deficiency and SLE and review the evidence from interventional studies.     

Cigarette smoking and the pathogenesis of systemic lupus erythematosus

Introduction: Systemic lupus erythematosus (SLE) is a multi-system inflammatory autoimmune disease of incompletely understood etiology. It is thought that environmental exposures ‘trigger’ or accelerate the disease in genetically-predisposed individuals.

Areas covered: Substantial epidemiological evidence exists to support the association between cigarette smoking and the risk of incident SLE. Recent evidence points to current smoking as the specific risk factor, with decreasing risk 5 years after smoking cessation, and the greatest risk for disease characterized by the presence of SLE-specific autoantibodies. Research has begun to search for possible explanations for the temporal nature of the relationship between current smoking and autoantibody positive-SLE. Here we review potential biologic mechanisms linking smoking and SLE risk, including effects upon T and B cells, inflammatory cytokines, oxidative stress, and the formation of short-lived DNA adducts.

Expert commentary: The directions for future research in this field include studies of gene-environment interactions, epigenetics, metabolomics and putative biologic mechanisms.     

系统性红斑狼疮多因子遗传的通径分析

本文应用ATRIBUTE软件对215例先证者及其核心家系进行了通径分析,以探讨SLE可能的遗传模式。结果表明,与一般模型比较,H＝0和（H＝0,C＝0）的假设被拒绝,提示SLE不符合单基因遗传,存在多基因遗传模式。本病可能是一多因子疾病,遗传度为49．9％。