肿瘤坏死因子α基因多态性与系统性红斑狼疮的相关研究

目的 探讨肿瘤坏死因子（tumor necrosis factor,TNF）α的基因多态性与华东地区汉族人群系统红斑狼疮（systemic lupus erythematosus,SLE)易感性的关系及其在SLE家系中的传递规律。方法 应用聚合酶链反应－限制性片段长度多态性对99例SLE患者，116名正常人及12个SLE家系的48名成员进行了TNFα基因分型。结果 SLE患者的TNFα等位基因频率高于对照组（8.6%vs3.4%,OR=2.63,P=0.00232)，在SLE家系研究中未发现TNFα基因多态性与SLE存在关联以及传递－连锁不平衡的证据。结论 TNFα2等位基因可能是SLE的易感等位基因。     

云南白族系统性红斑狼疮与HLA-DR、DQ相关性的研究

系统性红斑狼疮（ｓｙｓｔｅｍｉｃｌｕｐｕｓｅｒｙ－ｔｈｅｍａｔｏｓｕｓ,ＳＬＥ）的发病机理极为复杂。近年来研究表明,遗传因素在ＳＬＥ的发病中起决定性的作用。ＨＬＡ是迄今发现的最具多态性的遗传系统,它具有地区、种族、民族等的差异,其中ＨＬＡ－ＤＱ、ＤＲ等位基因的多态性与ＳＬＥ易感性是近几年研究的热点。我们运用单克隆抗体微量淋巴毒试验（ｍｏｎｏｃｌｏｎａｌａｎｔｉｂｏｄｉｅｓｍｉｃｒｏｃｙ－ｔｏｔｏｘｉｃｉｔｙａｓｓａｙ）［１］,探讨云南白族ＳＬＥ与ＨＬＡ－ＤＲ、ＤＱ的相关性。为进一步探讨ＳＬＥ免疫…     

肿瘤坏死因子β1069位点等位基因多态性与系统性红斑狼疮的相关性

目的 探讨江苏汉族人群肿瘤坏死因子β（tumor necrosis factor-β,TNFβ)1069位点等位基因多态性与系统性红斑狼疮的关系。方法 采用聚合酶链反应－限制性片段长度多态性方法对168名健康人和66例系统性红斑狼疮患者TNFβ基因的单碱基突变多态性进行了分析。结果 系统性红斑狼疮患者的TNFβ*2等位基因频率（67．4％）较正常人（55．1％）明显升高（P＝0．015，RR＝1．68）。结论 TNFβ*2等位基因与系统性红斑狼疮发病易患性相关。     

SLE患者血清可溶性肿瘤坏死因子受体水平及意义

目的探讨系统性红斑狼疮 (SLE)与可溶性肿瘤坏死因子受体 (sTNF R)的关系。方法利用双抗体夹心ELISA法检测了活动期SLE患者35例,稳定期患者25例及健康对照40例血清中sTNF RI和sTNF RII的水平。结果患者血清sTNF RI和sTNF RII的水平分别为(2.34±0.76)μg/L和(4.33±1.15)μg/L ;健康对照组分别为(1.09±0.11)μg/L和(2.05±0.29)μg/L ,患者明显高于健康对照组(P<0.01)。活动期SLE患者血清sTNF RI和sTNF RII水平分别为(2.93±0.32)μg/L和(5.19±0.53)μg/L ,明显高于稳定期SLE组分别为(1.46±0.15)μg/L和(3.04±0.28)μg/L(P∨0.01)。稳定期也明显高于健康对照组(P<0.01)。在SLE患者组中 ,血清sTNF RI和sTNF RII的水平与疾病活动积分呈显著的正相关(相关系数分别为0.76和0.69)(P<0.01) ;与抗ds DNA抗体水平亦呈显著的正相关(相关系数分别为0.67和0.58)(P<0.01) ;与补体C3的水平呈显著的负相关(相关系数分别为 -0.62和 -0.84)(P<0.01)。结论SLE患者血清sTNF RI和sTNFRII的水平明显增高 ,且与疾病的活动度呈显著正相关 ,这对于SLE的诊断及监测疾病的活动性 ,以及患者的判断预后可能是一种有用的实验室指标。     

我国北方地区Ⅰ型糖尿病患者与HLA-DR,DQ的关联研究

目的 研究我国北方胰岛素依赖型糖尿病人与ＨＬＡ－ＤＲ,ＤＱ的关联。方法 对华北地区５３名胰岛素依赖型糖尿病（ＩＤＤＭ）儿童进行了ＨＬＡ－ＤＲＢ１、ＤＱＡ１、ＤＱＢ１、分型,同１８５名进行了同样分型的华北正常对照人群进行关联分析。结果 发现ＤＲＢ１＊０３０１／ＤＲＢ１＊０４杂合子个体具有最高的风险（ＲＲ＝５１．１３）。进上不分析ＤＱ分子,将ＤＱα链第５２位为精氨酸和ＤＱβ链第５７位为非天冬氨酸分别命     

HLAⅡ类等位基因与系统性红斑狼疮自身抗体的关联

<正>系统性红斑狼疮（SLE）与HLAⅡ类等位基因相关。研究表明某些SLE自身抗体也与HLAⅡ类等位基因相关,且有报道其关联更强。本文探讨了我国汉族SLE与自身抗体的关系。     

系统性红斑狼疮患者淋巴细胞CD69表达及细胞因子水平研究

目的：通过检测系统性红斑狼疮患者外周血中淋巴细胞CD69^ 表达及CD69＋细胞分泌细胞因子的水平，探讨淋巴细胞活化和活化淋巴细胞因子的表达与系统性红斑狼疮的发病关系。方法：利用流式细胞分析法对系统性红斑狼疮患者动期13例、静止期23例和健康志愿者15例外周血中淋巴细胞的CD69^ 表达及其细胞内细胞因子（IL－2、TNFα）进行分析。结果：活动期和静止期系统性红斑狼疮患者淋巴细胞CD69^ 的表达均显著高于正常组（P＜0.05），系统性红斑狼患者淋巴细胞CD69^ 表达与SLEDAI具有明显的相关性（P＜0.05），而且活动期系统性红斑狼疮患者活化淋巴细胞内的细胞因子IL－2、TNFα表达较正常组显著升高（P＜0.05）。结论：系统性红斑狼疮患者体内存在淋巴细胞早期活化现象，与SLE发病程度相关。活化的淋巴细胞内细胞因子IL－2、TNFα呈高表达状态。     

肿瘤坏死因子受体Ⅱ196位点基因多态性与SLE相关性及功能研究

目的：调查中国汉族人群肿瘤坏死因子受体Ⅱ（TNFRⅡ）196位基因多态性与SLE的关系并构建野生和突变的逆转录病毒载体以研究其功能差异。 方法： 利用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测了106例SLE和119例健康人TNFRⅡ196位的基因型。扩增TNFRⅡ196M cDNA 克隆到PMD18-T载体上，定点突变为TNFRⅡ196R,然后亚克隆到逆转录病毒载体PLXSN上(PLXSN-TNFRⅡ196M和PLXSN-TNFRⅡ196R)并分别转染大鼠系膜细胞，以 ELISA法观察对系膜细胞产生IL-6的影响。 结果： (1)SLE组TNFR Ⅱ 196R等位基因型明显高于正常组（35.2% vs 14.3%,P<0.05）；(2)成功构建野生型和突变型重组逆转录病毒载体；（3）rhTNFα刺激后196R型转染系膜细胞产生IL-6明显高于196M型(P<0.05)。 结论： TNFRⅡ196R与中国汉族人群SLE相关，其可以高效转导TNFα的信号，可能参与SLE发病。     

中国汉人HLADQAl基因对系统性红斑狼疮的遗传易感性研究

利用ＨＬＡ基因的ＰＣＲ－ＲＦＬＰ核苷酸分型技术，以等位基因特异性的限制性内切酶（ＡｐａｌⅠ、ＢｓａｊⅠ、ＨｐｈⅠ、ＦｏｋⅠ、ＭｂｏⅡ、ＭｎｌⅡ）消化ＤＱＡｌ座位特异的ＰＣＲ扩增产物，研究了上海及其附近地区中国汉人ＨＬＡ－ＤＱＡｌ基因与系统红斑狼疮的遗传关联。发现系统红斑狼疮ＤＱＡｌ＊０１０２（３６．５％，ＲＲ＝２．２５，Ｐ＜０．０５，ＥＦ＝０．２０）及＊０４０１（１５．４％，ＲＲ＝１２．４２，Ｐ＜０．００５，ＥＦ＝０．１４）显著增加，而ＤＱＡｌ＊０５０１（１１．５％，ＲＲ＝０．２１，Ｐ＜０．００５，ＰＦ＝０．３１）和＊０．０６０１（３．９％，ＲＲ＝０．２７，Ｐ＜０．０５，ＰＦ＝０．０９）显著下降。排除ＤＱＡｌ＊０４０１的影响后，＊０１０２频率的升高表现得更加明显（ＲＲ＝２．８４，Ｐ＜０．０１）。上述发现显示：ＤＱＡｌ＊０１０２及＊０４０１对ＳＬＥ有遗传易感作用，而ＤＱＡｌ＊０５０１和＊０６０１有遗传抵抗作用，并提出了有关可能的单体型。     

抗内皮细胞抗体及内皮素在系统性红斑狼疮中的致病作用

目的：探讨抗内皮细胞抗体（ＡＥＣＡ）及内皮素（ＥＴ）与系统性红斑狼疮（ＳＬＥ）发病之间的关系。方法：采用ＥＬＩＳＡ法检测了４６例ＳＬＦ病人血浆中ＡＥＣＡ,并同步检测血浆内皮素水平。结果：发现活动期ＳＬＥ病人组ＡＥＣＡ阳性率明显较非活动期及正常对照组高,ＡＥＣＡ阳性的ＳＬＥ病人皮肤粘膜损害、浆膜炎、肾损害发生率较ＡＥＣＡ阴性病人明显增高,ＡＥＣＡ阳性组ＥＴ浓度也明显增高。结论：提示ＡＥＣＡ不仅直接参     

Autoantibodies Directed Against Ribosomal Proteins in Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Comparative Study

To assess the specificity of autoantibodies (aAbs) directed against the ribosomal P-proteins (RPPaAbs) in patients with systemic lupus erythematosus (SLE) and to investigate aAbs directed to other ribosomal proteins, 100 SLE, 100 rheumatoid arthritis (RA), 25 thyroiditis and 20 blood-donors were analyzed in a comparative study using an immunoblotting technique. Forty-eight percent of SLE sera contained aAbs directed against the ribosomal proteins of the 60 S subunit compared to 9% for RA, 5% for blood donors and 0% for thyroiditis. RPPaAbs were only found in SLE (25%) and aAbs directed to a 31 kDa and/or a 28 kDa protein of the 60 S subunit were found with a statistically higher frequency for SLE compared to RA (p <0.0001). aAbs directed to proteins of the 40 S subunit were present in 63% of the SLE sera compared to 42% for RA, 4% for thyroiditis and 5% for blood donors. The number of positive sera was not statistically different between SLE and RA but a much more intense reactivity was observed for SLE sera. These data shows that the aAbs against the ribosomal proteins, especially the P-proteins along with the 28 and 31 kDa proteins of the 60 S subunit proteins, can be considered as useful biological markers for the diagnosis of SLE in clinical practice.     

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.     

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.     

Take a look at the eyes in Systemic Lupus Erythematosus: A novel point of view

Systemic Lupus Erythematosus (SLE) is a connective tissue disease that involves multiple organs. Ocular structures and visual pathways can be affected in SLE because of disease-related eye involvement or drug toxicity. All the part of the eye may be interested with an external, anterior involvement, responsible of the dry eye disease, or posterior (retina) and neuro-ophtalmic manifestations. Retinopathy in SLE is suggestive of high disease activity being a marker of poor visual outcome and prognosis for survival. The early diagnosis is thus the key to a better management and successful treatment. Antimalarial drugs are the cornerstone of SLE treatment and recently the American Academy of Ophthalmology updated the recommendations for hydroxychloroquine retinal toxicity screening which includes the standard automated visual fields and the spectral domain optical coherent tomography. More recently new imaging techniques have been investigated to assess retinal function and reveal subclinical eye involvement. In this review we focalize on the evidence of eye manifestations in SLE, the eye drug toxicity related to antimalarial agents and steroids, and the methods employed for the eye screening. Moreover, the future perspectives on new techniques, such as the optical coherence tomography angiography, are dissected giving new insights on evaluation of microvasculature of the retina and choroid in SLE.     

The Role of Apoptosis Proteins and Complement Components in the Etiopathogenesis of Systemic Lupus Erythematosus

Systemic lupus erythematosus is a prototypical autoimmune disease characterized by the deregulation of T and B cells, tissue infiltration by mononuclear cells, tissue damage and the production of autoantibodies. There is a consensus that accelerated apoptosis of circulating lymphocytes and/or impaired clearance of apoptotic bodies may increase the amount of nuclear antigens presented to T lymphocytes. This process is accompanied by autoimmune responses that can lead to the development of lupus. The dysfunction of apoptosis may be a direct consequence of alterations in proteins/genes such as Fas, Bcl-2 and C1q. Increased expression of Fas antigen could intensify the exposure of hidden antigens. The overexpression of Bcl-2 protein might inhibit the removal of auto-reactive cells, and the lack of C1q could impair the clearance of self-antigens. The complete knowledge of the role of apoptosis components in the etiopathogenesis of lupus could lead to the development of new therapies targeting the apoptotic threshold, which could result in a more specific and effective disease response compared to global immunosuppression. This review summarizes the role of each component of the apoptotic process in the pathogenesis of lupus.     

Subpopulations of Regulatory T Cells in Rheumatoid Arthritis, Systemic Lupus Erythematosus, and Behcet's Disease

Recently, subpopulations of regulatory T (Treg) cells, resting Treg (rTreg) and activated Treg (aTreg), have been discovered. The authors investigated the relationship between the change of Treg, aTreg and rTreg and autoimmune diseases. Treg cells and those subpopulations were analyzed by using the human regulatory T cell staining kit and CD45RA surface marker for 42 rheumatoid arthritis (RA), 13 systemic lupus sclerosis (SLE), 7 Behcet's disease (BD), and 22 healthy controls. The proportion of Treg cells was significantly lower in RA (3.8% ± 1.0%) (P < 0.001) and BD (3.3% ± 0.5%) (P < 0.01) compared to healthy controls (5.0% ± 1.3%). The proportion of aTreg cells was also significantly lower in RA (0.4% ± 0.2%) (P = 0.008) and BD (0.3% ± 0.1%) (P = 0.013) compared to healthy controls (0.6% ± 0.3%). The rTreg cells showed no significant differences. The ratio of aTreg to rTreg was lower in RA patients (0.4% ± 0.2%) than that in healthy controls (0.7% ± 0.4%) (P = 0.002). This study suggests that the decrement of aTreg not rTreg cells contributes the decrement of total Treg cells in peripheral blood of RA and BD autoimmune diseases. Detailed analysis of Treg subpopulations would be more informative than total Treg cells in investigating mechanism of autoimmune disease.     

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.     

藻酸双酯钠(PSS)对系统性红斑狼疮患者血液流变性的影响

目的 :探讨藻酸双酯钠 (PSS)对系统性红斑狼疮患者血液流变性的影响。方法 :通过临床观察单用激素组与并用PSS组治疗前后血液流变性的变化 ,以LG R 80 (A)型血液流变仪进行相关指标检测。结果 :单用激素组治疗前后患者的血浆粘度及红细胞聚集指数轻度升高 ,其他指标无明显变化 ;并用PSS组治疗后低切全血粘度、红细胞聚集指数、纤维蛋白原等均显著降低。结论 :PSS能明显改善SLE患者的高血凝状态 ,并可减轻激素的副作用。