Serum factors from patients with systemic lupus erythematosus enhancing superoxide generation by normal neutrophils

It has been suggested that human neutrophils exposed to performed immune complexes or activated complement fragments generate O2- anions in extracellular medium. In vivo studies have revealed that oxygen intermediates produced by immune complex-activated neutrophils play an important role in subsequent tissue damage. Since it is difficult to obtain direct evidence that O2- is released into plasma in patients with systemic lupus erythematosus (SLE), we studied the capacities of their sera to stimulate O2- release by human neutrophils in vitro. Sera from patients with SLE significantly enhanced O2- generation by neutrophils compared to normal sera. The enhancing activity of serum in the induction of increased O2- generation correlated positively with the presence of serum immune complexes and negatively with serum complement levels. The enhancing factors were analyzed by serum fractionation on Sephadex G-200 gel filtration, and were concluded to be immune complexes of intermediate size containing an activated complement fragment.     

系统性红斑狼疮患者血清几种趋化因子的检测

目的 探讨血清趋化因子单核细胞趋化及活化因子/单核细胞趋化蛋白-1(MCAF/MCP-1)、正常T细胞表达和分泌的活化调节蛋白(RANTES)水平与系统性红斑狼疮疾病活动程度的关系及意义。方法 采用双抗体夹心ELISA法检测血清MCAF、RANTES水平。结果 ①SLE患者血清MCAF水平明显高于正常人;②活动期患者血清MCAF水平明显高于非活动期;③肾损组与非肾损组相比,血清MCAF、RANTES水平差异均无显着性。结论 趋化因子MCAF可能参与系统性红斑狼疮的发病机制,且血清MCAF水平可作为反映疾病活动性的一个指标。     

SLE患者血清、尿液和肾脏骨桥蛋白的检测及临床意义

目的 探讨骨桥蛋白(OPN)在SLE患者血清、尿液中的含量及与SLE脏器损害、活动性指标的关系.方法 收集100例SLE患者临床资料,ELISA方法检测OPN在100例SLE患者和30例正常人对照外周血清中的浓度,同时用ELISA检测OPN在57例SLE患者和15例正常人对照尿液中的浓度.免疫组化检测3例SLE患者肾脏组织中OPN蛋白的表达.结果 OPN在SLE患者血清和尿液中浓度显著升高,分别为(64.03±72.87)μg/L和(454.87±231.63)μg/L,与正常对照组[(29.88±11.28)μg/L,(122.67±39.47)μg/L]相比,差异有统计学意义(P<0.05), SLE活动组血清和尿液中OPN浓度显著升高,分别为(80.92±87.49)μg/L和(584.36±207.15)μg/L,与SLE非活动组[(36.43±23.48)μg/L,(281.08±131.92)μg/L]相比,差异有统计学意义(P<0.05).血清和尿液中OPN浓度均和SLEDAI积分呈正相关(r=0.462,0.901,P值均<0.01).尿液OPN浓度和尿免疫球蛋白G、尿微量白蛋白、尿α1微球蛋白、尿B2微球蛋白呈正相关(r=0.458,0.359,0.342,0.409,P值均<0.05).OPN在狼疮性肾炎患者肾小管上皮表达.结论 OPN与SLE及肾损有密切关系.     

SLE疾病活动性与补体及免疫球蛋白水平相关性的探讨

目的 :　探讨SLE患者治疗过程中疾病活动性与血清补体及免疫球蛋白水平的相关性。方法 :以SLAM评估 2 0 4例患者疾病活动性 ,并对其中 2 6例初诊患者行 15个月的追踪观察。速率散射比浊法测定血清C3、C4 、IgG、IgA、IgM水平。结果 :　高度活动组患者C3、C4 、IgG水平与非活动组及中度活动组均有显著差异 (P <0 .0 5 ) ,但中度活动组与非活动组间所有指标均无显著差异 (P >0 .0 5 )。高度活动组患者治疗初期SLAM分值与C3、C4 、IgG水平相关 ,但随疾病活动性下降到一定程度后便失去相关性。结论 :不能单凭C3、C4 、IgG水平变化判断SLE疾病活动性或调整用药。IgA、IgM水平与疾病活动性未见相关     

Polymorphonuclear leukocyte chemotaxis in psoriasis: enhancement by self-activated serum

The chemotactic activity of polymorphonuclear leukocytes (PMNs) directed against serum was determined in a modified Boyden chamber assay. In a total of 176 experiments PMNs and sera from healthy controls were compared with PMNs and sera from patients with psoriasis. When PMNs from patients with psoriasis were confronted with psoriatic serum greatly enhanced chemotaxis was demonstrated. Non-psoriatic PMNs in the presence of psoriatic serum showed no enhancement. However, psoriatic PMNs in the presence of normal serum were chemotactically more active compared to non-psoriatic PMNs. Heat inactivation (56°C, 30 min) reduced the chemotactic activity of all sera by nearly 50%. However in psoriatic sera the enhancement of chemotaxis was still present after heat treatment. The results indicate the presence of a functional abnormality of chemotaxis in psoriasis. This is likely to be caused by the in situ generation of chemotactically active fragments of complement. Experiments showing increased chemotactic activity of sera exposed to migrating PMNs support this concept.     

Viral immune complexes in systemic lupus erythematosus: C-type viral complex deposition in skin.

Punch biopsies were examined by indirect immunofluorescence for immune complex deposits containing C-type viral antigen. Antisera specific for immunoglobulins and HEL-12 virus mediated fluorescence at the dermal-epidermal junction and in vessel walls of 16 of 16 biopsies involved skin from patients with systemic lupus erythematosus (SLE). Preimmune sera did not mediate fluorescence and gradient purified HEL-12 virus, simian sarcoma virus and baboon endogenous virus but not Rous sarcoma virus blocked the reaction of anti-HEL-12 virus serum with SLE tissue. Ten biopsies from uninvolved skin of the patients with SLE did not react with the antiviral serum, nor did tissue from 9 patients with discoid lupus erythematosus, psoriasis, bullous pemphigoid or normal skin. These data support the hypothesis that C-type viral immune complexes participate in the pathogenesis of SLE.     

Removal of a blocking factor from the sera of patients with systematic lupus erythematosus with Levamisole

A factor in the sera of patients with systemic lupus erythematosus (SLE) reduced the response of their lymphocytes to phytohaemagglutinin (PHA) demonstrated by mixed leukocyte migration inhibition. Lymphocyte responses to PHA in horse serum were unimpaired. After treatment with Levamisole for 3 months, responses to PHA in autologous sera returned to normal.     

Activation/inactivation of the classical pathway of complement in non-lesional skin of patients with systemic lupus erythematosus

BACKGROUND: The link between the lupus band and pathogenesis remains controversial, because immunoglobulins and complement components, including the membrane attack complex, can be found in both lesional and non-lesional skin of patients with systemic lupus erythematosus (SLE). The expression of proteins that regulate complement has not been previously investigated in the skin of patients with SLE. AIM: The aim of this study is to compare the expression of protectin (CD59), which demonstrates the activation of the classical pathway of complement, in non-lesional skin obtained from patients with SLE with its expression in normal skin. This may help us explain the link between the lupus band and pathogenesis of cutaneous lupus erythematosus. METHODS: An indirect immunofluorescence technique was performed in order to provide unequivocal evidence for the activation of complement via the classical pathway and to compare the expression of CD59 in non-lesional skin from patients with SLE with normal skin samples obtained from healthy people. RESULTS: The activation of the classical pathway of complement was demonstrated in non-lesional skin in more than 90% of SLE patients investigated in this study. Staining intensity of the complement regulatory protein CD59 was markedly increased in the majority of non-lesional skin samples obtained from patients with SLE, compared to that from normals. Conclusions: CD59 is overexpressed in non-lesional skin in which complement activation has occurred. It seems likely that an increased and continuous CD59 expression may be important for maintaining the integrity of the skin BMZ during inflammatory responses involving complement activation in SLE skin. Alahlafi A, Wordsworth P, Wojnarowska F. Activation/inactivation of the classical pathway of complement in non-lesional skin of patients with systemic lupus erythematosus.     

Interferon response to dipyridamole in lupus erythematosus patients

Studies in patients with autoimmune disorders strongly support a role for interferon (IFN) in the disease process. In the present study we investigated the in vivo production of alpha-IFN in lupus erythematosus patients after stimulation with dipyridamole, recently characterized as an alpha-IFN inducer in mice and humans. Levels of IFN were measured in serum samples from 22 patients with systemic lupus erythematosus (SLE) and 12 patients with discoid lupus erythematosus (DLE) before and 24 h after dipyridamole administration. IFN activity was assayed on human and bovine cells in parallel. Initial serum concentrations of alpha-IFN in SLE patients were markedly elevated. The percentage of DLE positive responders to dipyridamole induction was about twice as high as that found for SLE. Studies of factors responsible for IFN production in lupus erythematosus might result in better understanding of the relationship between DLE and SLE.     

女性系统性红斑狼疮患者血清瘦素水平的检测及意义

目的：探讨女性系统性红斑狼疮患者血清瘦素水平的变化。方法：采用放射免疫分析法对54例女性系统性红斑狼疮患者及30例正常对照组血清瘦素水平进行了检测。结果：女性系统性红斑狼疮患者血清瘦素水平明显高于正常对照组，差异有显著性；月经周期正常者、月经周期紊乱者、闭经者血清瘦素水平明显高于正常对照组，差异有显著性；有肾脏损害及无肾脏损害患者血清瘦素水平亦升高，与正常对照组相比，差异有显著性。结论：女性系统性红斑狼疮患者血清瘦素水平的变化可能与系统性红斑狼疮的发病有关。     

SLE患者血清C3、C4及免疫球蛋白水平与疾病活动性的关系

目的测定系统性红斑狼疮（systemic lupus erythematosus,SLE）患者血清补体C3、C4及免疫球蛋白水平,并进一步探讨它们与SLE临床表现及病情的相关性。方法采用散射比浊法测定92例SLE患者血清中补体C3、C4及免疫球蛋白水平。结果随着SLEDAI评分增加,血浆C3、C4水平逐渐降低,C4水平与病情活动成负相关,IgG水平略有增加;SLEDAI评分可有效表明治疗效果,激素使用量与补体C3、C4水平成反比,与IgG水平成正比,但无统计学差异;SLE的不同系统损害与血浆中C3、C4免疫球蛋白的表达水平无相关性。结论动态观察SLEDAI评分、C3、C4及免疫球蛋白的水平对SLE的病情活动度、治疗的选择及预后的判断有重要意义。     

系统性红斑狼疮患者血清生长激素和泌乳素动态变化的研究

目的 探讨ＳＬＥ患者生长激素和泌乳素对促甲状腺激素释放激素反应。方法 用双抗体ＲＩＡ法测定促甲状腺激素释放激素注射前及注射后１５、３０、６０、１２０ｍｉｎＳＬＥ患者和正常人对照组的血清生长激素和泌乳素。结果 ＳＬＥ活动期患者注射前和注射后１５、３０、６０、１２０ｍｉｎ血清泌乳素水平以及在６０、１２０ｍｉｎ时血清生长激素水平显著高于ＳＬＥ静止期及正常人对照组（Ｐ〈０．０１）；ＳＬＥ静止期与正常人对照     

Mononuclear cell versus monocyte chemotaxis in psoriasis

Chemotaxis under agarose of psoriatic mixed mononuclear cells (MNs) and pure monocytes against Zymosan treated sera (ZAS), fresh psoriatic serum, and fresh normal serum was studied and compared with that of normal cells. Purification of monocytes was achieved on microexudate coated BHK flasks. Psoriatic MNs were found to be more chemotactic against psoriatic serum (P.S.) than normal MNs against normal serum (N.S.). Psoriatic cells were chemotactically more active than normal ones against psoriatic and normal serum but not against ZAS. Mixed mononuclear cells showed definitely increased chemotaxis over that of pure monocytes. When culture supernatants with lymphocyte derived factor (LDCF) activity were mixed with normal pure monocytes, the chemotactic activity of the monocytes recovered. It is, therefore, proposed that the LDCF from in vivo stimulated psoriatic lymphocytes by antigenic or mitogenic substances of psoriatic plaque might be an essential factor for the increased chemotaxis of mixed psoriatic MNs compared to pure monocytes. This hypothesis also explains the increased chemoattracting capacity of psoriatic serum for psoriatic and normal MNs as due to the in vivo release of lymphokine.     

A study of anti-carbonic anhydrase II antibodies in rheumatic autoimmune diseases.

Autoantibodies to human carbonic anhydrase II (CAII) were screened by ELISA in 109 sera from Asian Japanese patients with systemic lupus erythematosus (SLE), primary Sj?gren's syndrome (Sjs), progressive systemic sclerosis (PSS) and dermatomyositis (DM). Anti-CAII antibodies were positive in 24.1% of SLE, 20.0% of primary Sjs, 16.7% of PSS and 25.0% of DM. On the other hand, sera from atopic dermatitis, bullous pemphigoid and psoriasis patients showed no activity for anti-CAII antibodies. CAII could be a common exonuclear autoantigen in subsets of rheumatic autoimmune diseases.     

Antibodies to UV DNA and photosensitivity

Antibodies to ultraviolet light denatured DNA (UV DNA) have been measured in the sera of patients with systemic lupus erythematosus, discoid lupus erythematosus, and light sensitive skin lesions. Antibodies were found in significant levels in the patients with SLE but not in the other groups. It appears that although UV denaturation of dermal DNA occurs in vivo this is not sufficient to induce antibodies to UV DNA in patients with a normal DNA repair mechanism. This may not be the case in patients with SLE in whom a break in tolerance to Native (N-) DNA has already occurred and where antibody to N-DNA will cross react with UV DNA.     

SLE患者红细胞CR1与IL-8R的表达

目的:研究红细胞CR1和IL-8R在系统性红斑狼疮患者(SLE)中的表达及两者之间的相关性。方法:分别用V型板红细胞离心洗涤免疫酶联法和酶联免疫吸附试验检测活动期SLE患者44例、稳定期SLE42例红细胞CR1及IL-8R的表达,并与健康人作对照,CR1与IL-8R之间的相关性采用Sperman相关分析。结果:活动期SLE患者红细胞CR1和IL-8R较健康人对照组和稳定期SLE患者的表达水平显著下降(P<0.001);稳定期SLE组与健康人对照组比较,CR1和IL-8R分子的表达差异无显著性(P>0.05);活动期SLE的CR1表达与IL-8R的结合活性呈正相关,即活动期SLE的红细胞CR1数量表达和IL-8R的结合活性都显著降低。结论:活动期SLE患者的红细胞CR1免疫识别、黏附、清除CIC能力下降,可能是SLE免疫发病机制中的一个重要环节;CR1及IL-8R在SLE发病机制中可能起重要作用;CR1和IL-8R有可能作为SLE患者病情是否活动、药物疗效判断的一个有价值的辅助指标。     

c-FLIP在SLE患者外周血B细胞的表达及与临床特征的相关性研究

目的 探讨SLE患者外周血B细胞凋亡抑制蛋白c-FLIP的表达及其与临床特征的相关性。方法 53例SLE患者和30例正常人对照组,采用流式细胞术检测外周血B细胞c-FLIP表达阳性率,采用ELISA方法检测血清中IL-4和IL-10的水平。结果 活动期SLE患者（18例）外周血B细胞内c-FLIP表达（3.11% ± 0.70%）明显高于非活动期患者（35例）（0.78% ± 0.28%）和正常人对照组（0.68% ± 0.12%）（P均 < 0.05）,而非活动期组和正常人对照组比较,差异无统计学意义（t = 1.56,P > 0.05）。SLE患者外周血B细胞c-FLIP的表达与SLEDAI、ESR、C反应蛋白、ANA 滴度均呈正相关（P均 < 0.05）;伴有WBC减少的36例SLE患者中c-FLIP的表达与WBC的数目呈负相关（P < 0.01）。伴有狼疮肾炎的23例SLE患者的外周血B细胞内c-FLIP的表达（3.04% ± 1.09%）明显高于30例不伴狼疮肾炎者（1.76% ± 1.09%）（t = 4.23,P < 0.05）。SLE患者c-FLIP的表达与血清中IL-4和IL-10的水平均呈正相关（P均 < 0.01）。结论 活动期SLE患者外周血B细胞c-FLIP高表达,且与SLE病情严重程度正相关。同时其表达水平与SLE患者血清中IL-4和IL-10水平呈正相关。     

系统性红斑狼疮女性患者血清免疫球蛋白和补体与年龄的关系

目的探讨系统性红斑狼疮(SLE)患者血清免疫球蛋白和补体与年龄的关系。方法用免疫散射比浊法检测218例女性SLE患者及98名正常对照组女性的血清免疫球蛋白和补体,分析其与年龄的关系。结果女性SLE患者血清IgM水平(1.069±0.553)与正常对照组(1.161±0.443)相比,差异无统计学意义(P>0.05),血清IgG(17.515±5.845)和IgA(3.282±1.672)水平均显著高于正常对照组(12.668±2.918和2.315±0.750),但血清C3(0.895±0.327)和C4(0.156±0.086)水平均显著低于正常对照组(1.160±0.183和0.245±0.065),差异均有统计学意义(P均<0.01);血清IgA,C3和C4水平与年龄呈正相关(P均<0.05),而正常对照组免疫球蛋白和补体水平则与年龄无关(P均>0.05)。结论女性SLE患者血清IgG,IgA,C3和C4存在异常,IgA,C3和C4的异常与年龄相关。     

Th17在SLE的组织定位和外周血单一核细胞中的比例

目的 探讨产生IL-17的CD4+T细胞(Th17)在SLE患者组织中的定位,以及与狼疮活动的关系.方法 共聚焦显微镜、免疫荧光双标技术、免疫组化和HE染色,分析Th17细胞业群在4例活动期SLE患者和2例正常人外周血单一核细胞中、皮损组织和肺组织中的定位.流式细胞仪检测50例SLE患者和15例正常人对照外周血Th17的比例,RT-PCR检测相关细胞因子基因表达,用ELISA检测血清中IL-17的分泌水平.结果 在活动期狼疮患者外周血单一核细胞中可见有Th17细胞,其IL-17的荧光强度为(127.6±20.5),明显高于正常人IL-17荧光强度,其值为(40.6±11.1),P＜0.001.在活动期SLE患者受损的皮肤组织和肺组织中可见有Th17细胞的浸润,而正常人皮肤未见有Th17细胞的浸润.活动期SLE患者外周血中Th17比例明显增加,且与SLE活动指数(SLEDAI)呈正相关.相关细胞因子IL-17A和IL-17F mRNA表达明显增加,血清中的不IL-17水平分泌增加,活动期SLE患者中Th17增加与血管炎的发病呈正相关,经过治疗后Th17随病情缓减而减少.结论 Th17细胞亚群在活动期SLE患者体内扩增,其扩增与SLE活动密切相关,可能参与SLE 血管炎的发生.     

SLE患者血清补体第二途径激活的探讨

本文研究SLE发病过程中血清补体替代途径的活化.对36例SLE患者同时测定血清补体ACH₅₀,B因子、CH₅₀,C₃和C₄,其结果表明除经典途径活化外,替代途径亦被激活.其B因子不仅与SLE发病有关,而且与疾病的活动性相关.B因子的变化与C₃,C₄变化相一致,尤其在活动性SLE.