Clinical analysis of anti-cardiolipin antibody positive patients with systemic lupus erythematosus

We have analyzed the relationship between anti-cardiolipin antibody titer and manifestations in 68 patients with systemic lupus erythematosus (SLE), 25 patients with progressive systemic sclerosis (PSS), 37 patients with Sj?gren's syndrome and 16 patients with anaphylactoid purpura. Elevated anti-cardiolipin antibody titer was observed in SLE and Sj?gren's syndrome. Clinical manifestations correlated with elevated anti-cardiolipin antibody titer included discoid lesion, thrombotic lesion, thrombocytopenia, elevated titer of ds-DNA antibodies, lower serum CPK level, and liver dysfunctions. Anti-cardiolipin antibody titer also correlated with the score of diagnostic criteria for SLE and the history of corticosteroid therapy. These results suggested that anti-cardiolipin antibody positive SLE patients are much more prone to develop thrombotic lesions and that cell bound antibody might play some role for the induction of vascular injury and thrombocytopenia in SLE.     

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.     

The lupus anticoagulant in systemic lupus erythematosus and systemic sclerosis

The lupus anticoagulant is an acquired IgG or IgM antibody directed against specific phospholipids involved in the formation of prothrombin activators. It is identified by coagulation tests. The partial thromboplastin time and kaolin clotting time are prolonged and these abnormalities cannot be corrected by the addition of normal plasma, as in simple clotting factor deficiency. The thrombin time is normal.
Five out of 36 unselected patients with systemic lupus erythematosus (SLE) showed the presence of lupus anticoagulant (14%). The duration of SLE was from 2 to 38 years. Three of the five patients gave a history of thrombosis. The only male patient suffered from myocardial infarction and venous thromboses in his twenties and is an example of a group of young males with major thrombotic episodes. One patient had a Coombs-positive haemolytic anaemia. Thrombocytopenia is sometimes associated with the lupus anticoagulant but was not found in the present series. Anticardiolipin antibodies were not measured, but none of the patients had false-positive serology.
The lupus anticoagulant is a useful marker for those patients with SLE at risk for thrombosis.
The lupus anticoagulant was not found in 24 unselected patients with systemic sclerosis and is therefore not a factor in the pathogenesis of the vascular phenomena in this disease.     

血浆骨桥蛋白水平与系统性红斑狼疮活动性的关系

目的 探讨血浆骨桥蛋白与系统性红斑狼疮(SLE)活动程度的关系。方法 采用ELISA方法检测28例健康人与38例SLE患者血浆骨桥蛋白水平,以分析其与SLE活动性变化关系。结果 SLE患者血浆骨桥蛋白水平(420±203)ng/mL明显高于正常对照组(73±14)ng/mL,P<0.001;SLE蛋白尿组(623±88)ng/mL明显高于非蛋白尿组(288±135)ng/mL,P<0.001;活动组(529±143)ng/mL明显高于非活动组(185±66)ng/mL,P<0.001;糖皮质激素治疗后血浆骨桥蛋白水平(142±22)ng/mL与治疗前水平(556±130)ng/mL相比,差异有统计学意义(P<0.001);关节炎组(489±153)ng/mL与非关节炎组(375±222)ng/mL之间差异无统计学意义,P>0.05。血浆骨桥蛋白水平与SLE DAI呈正相关,r=0.93,P<0.001;与C3呈负相关,r=-0.49,P<0.05;与ANA滴度、血细胞沉降率、C4水平无相关性(P>0.05)。结论 血浆骨桥蛋白水平变化与SLE活动程度、肾脏损害及疾病进展有关。     

系统性红斑狼疮患者生长激素及其受体和泌乳素水平的研究

用放射免疫分析法（ＲＩＡ）和放射受体分析法（ＲＲＡ）检测３４例系统性红斑狼疮（ＳＬＥ）患者和２０例正常人血清生长激素（ＧＨ）和泌乳素（ＰＲＬ）水平及其生长激素受体（ＧＨ－Ｒ）容量。结果显示ＳＬＥ患者血清ＧＨ和ＰＲＬ水平均显著高于正常对照组，血清ＧＨ－Ｒ容量与正常对照组相比无显著差异。ＳＬＥ患者血清ＧＨ增高与病情活动度和抗ｄｓＤＮＡ抗体水平增高密切相关，而ＰＲＬ无此关系。我们推测在ＳＬＥ的发病过程中     

系统性红斑狼疮患者血清抗核小体抗体水平检测及其临床意义

目的探讨抗核小体抗体(AnuA)水平与红斑狼疮(LE)疾病亚型及其治疗前后的关系。方法采用酶联免疫吸附法(ELISA)测定31例系统性红斑狼疮(SLE)、26例亚急性皮肤型红斑狼疮(SCLE)、7例盘状红斑狼疮(DLE)、6例硬皮病、5例皮肌炎患者和30例健康人血清AnuA水平,根据SLE患者临床表现及实验室检查指标,进行SLE疾病活动指数(SLEDAI)评分,并对LE患者AnuA进行治疗前后的比较。结果SLE患者血清AnuA水平与SCLE、DLE、硬皮病、皮肌炎患者和正常对照组相比显著增高(P均<0.01);SLE活动期患者血清AnuA水平与SLE非活动期相比显著增高(P均<0.01);SCLE、DLE、硬皮病患者血清AnuA水平两两相比差异无统计学意义(P>0.05),与皮肌炎、正常对照组相比差异有统计学意义(P<0.05);皮肌炎患者和正常人对照组相比差异无统计学意义(P>0.05)。AnuA水平与SLEDAI有明显相关性(P=0.015,r=0.441),SLE患者治疗后血清AnuA水平与治疗前相比明显降低(P<0.05)。结论AnuA水平与LE的亚型和是否活动有相关性,对诊断疾病、监测病情活动和判断疗效有意义。     

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。     

Oxidative protein damage and antioxidant status in systemic lupus erythematosus

Background. Oxidative stress may play a role in the pathogenesis of systemic lupus erythematosus (SLE). Proteins are one of the main targets for oxidants, due to their abundance in biological systems and their high rate constants for reaction. Aim. To evaluate differences in oxidative protein damage and antioxidant status between patients with SLE and healthy controls, and to explore whether oxidative protein damage has a role in either the disease activity or the organ damage in SLE. Methods. Using spectrophotometry and ELISA, the levels of multiple markers of protein oxidation and antioxidant status in the serum of 62 patients with SLE and 62 healthy controls were evaluated. Results. We found that levels of multiple markers of protein oxidation and activities of superoxide dismutase (SOD) and myeloperoxidase were increased, whereas levels of protein thiol and activities of glutathione peroxidase and catalase were reduced in serum from patients with SLE compared with controls. Disease activity index correlated positively with erythrocyte sedimentation rate and levels of serum protein carbonyl (PC), 3‐nitrotyrosine and C‐reactive protein, and negatively with levels of serum protein thiols and activities of SOD, glutathione peroxidase and catalase activities in patients. There was a significant difference in the serum PC levels between patients with and without arthritis or arthralgia. The same was true when patients with and without cardiac involvement, and patients with and without renal disease were analysed. Conclusions. The findings suggest that protein oxidation may play a role in the pathogenesis of chronic organ damage in SLE.     

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、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.     

Assessment of serum vascular endothelial growth factor and nail fold capillaroscopy changes in systemic lupus erythematosus with and without cutaneous manifestations

Angiogenesis and microvascular endothelial injury play a role in the pathogenesis of systemic lupus erythematosus (SLE). Vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, and nail fold capillaroscopy (NFC) have been investigated in few studies in SLE with no reports targeting SLE with cutaneous manifestations. To evaluate NFC changes and VEGF serum level in relation to disease activity in SLE patients with versus without cutaneous manifestations. Thirty SLE patients (15 with cutaneous manifestations [group I], 15 without [group II]) and 15 healthy controls were evaluated for VEGF serum levels, NFC changes and were related to disease activity. VEGF serum levels were significantly higher in patients than controls (median and interquartile range [IQR]: 2110.77, 471.09-4714.30 vs. 60.00, 14-366, respectively, P?相似文献   

系统性红斑狼疮脱发的研究进展

脱发是SLE常见的临床表现之一。SLE脱发可表现为多种类型,如狼疮发、非瘢痕性斑状脱发、弥漫性休止期脱发、盘状红斑狼疮型脱发等,不同类型的脱发在临床表现和组织病理学方面有其各自的特点。SLE脱发与疾病活动性有一定的相关性。目前SLE脱发的发病机制尚未明确,自身免疫性炎症和血管炎造成的局部微环境的改变、毛发营养不良和毛囊周期失调均有可能参与其中。     

SLE患者血清抗中性粒细胞胞质抗体的临床意义

目的 探讨抗中性粒细胞胞质抗体（ANCA）与SLE的关系及其临床意义。方法 选择60例SLE新发病例和60例正常人对照，用ELISA法将其分为ANCA阳性和阴性组，调查表收集所有患者的一般情况、临床表现及实验室检查。结果 60例SLE新发病例中ANCA阳性率为33.3%，对照组中ANCA阳性率为3.3%，两组差异具有统计学意义（P < 0.001）。SLE活动组ANCA阳性率（84.62%）显著高于非活动组（19.15%，P < 0.01）。ANCA阳性组中神经系统紊乱、心肌炎、肾损害、浆膜炎、抗dsDNA抗体阳性、抗Sm抗体阳性、γ-球蛋白升高、补体下降以及血清IgG升高的发生率明显高于阴性组（P < 0.05）。ANCA阳性组中，SLE疾病活动指数评分（SLE-DAI）（24.40 ± 10.16）及ESR（84.45 ± 29.03）显著高于阴性组的SLE-DAI（11.30 ± 6.07）及ESR（47.07 ± 26.31）（P < 0.05）。狼疮性肾炎（LN）组ANCA阳性率（46.7%）显著高于非狼疮性肾炎（非LN）的SLE组（21.9%，P < 0.05）。结论 ANCA可作为评价SLE疾病活动及鉴别LN与非LN的一个参考指标。     

SLE患者96例血脂检测及临床意义分析

目的　探讨SLE患者脂代谢与疾病活动性及其他临床表现的关系。方法　分别检测96例未经治疗的SLE患者及50例正常体检者血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇,比较两组间血清脂质水平的差异及与SLE患者临床表现和病情活动的关系。结果　SLE患者组血清三酰甘油水平明显高于正常对照组,高密度脂蛋白胆固醇水平明显低于对照组。SLE血脂异常组中肾炎、肾病综合征、抗dsDNA抗体、抗RNP抗体、抗核糖体P蛋白抗体、核周型抗中性粒细胞胞质抗体阳性率明显高于SLE血脂正常组,补体C3、C4水平明显低于血脂正常组;稳定期SLE高密度脂蛋白胆固醇水平明显高于活动期。结论　未经治疗的SLE患者即已存在血脂异常,主要表现为三酰甘油增高和高密度脂蛋白胆固醇降低。其异常主要与肾损害有关,且与病情活动有一定的相关性。     

The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score

Background There is increased expression of type I interferon (IFN)‐regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Patients with SLE have increased IFN‐regulated gene expression pointing towards a possible underlying genetic defect. Objectives To determine expression levels of five type I IFN‐regulated genes that are highly expressed in SLE in the peripheral blood of patients with CLE and to correlate the expression levels with cutaneous disease activity. Methods Peripheral blood was obtained from 10 healthy controls and 30 patients with CLE, including eight with concomitant SLE. Total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real‐time polymerase chain reaction. Gene expression was normalized to GAPDH, standardized to healthy controls and then summed to calculate an IFN score for each patient. Disease activity was assessed with the Cutaneous Lupus Area and Severity Index (CLASI). Results Patients with subacute CLE (SCLE) and discoid lupus erythematosus (DLE) had elevated IFN scores compared with healthy controls regardless of concomitant SLE (P < 0·01 with SLE and P < 0·05 without SLE). There was no difference between patients with tumid lupus erythematosus (TLE) and healthy controls. The IFN score correlated with CLASI scores (Spearman’s rho = 0·55, P = 0·0017). Conclusions Patients with SCLE and DLE have an IFN signature, as seen in SLE. The level of gene expression correlates with cutaneous disease activity. These findings support a shared pathogenesis between SLE and some subtypes of CLE.     

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.     

血清PS-PLA1水平与系统性红斑狼疮疾病活动相关性分析

目的:探讨磷脂酰丝氨酸-特异性磷脂酶A1(PS-PLA1)与系统性红斑狼疮(SLE)疾病活动的相关性.方法:收集SLE患者及健康对照,对患者进行SLEDAI评分,采用酶联免疫吸附法(ELISA)测定两组血清中PS-PLA1表达水平,分析PS-PLA1与SLE疾病活动的相关性.结果:共收集SLE患者101例(活动组70例...     

Effect of human recombinant interleukin-Iα on release of prostacyclin from human endothelial cells

Incubation of human recombinant IL-1 alpha (hrIL-1 alpha) with cultured human endothelial cells induced a dose- and time-dependent increase in the release of prostacyclin (PGI2). Above a dose of hrIL-1 alpha 0.05 units/ml and following a variable lag phase of between 2 and 4 h, PGI2 release (measured as the stable hydrolysis product 6-keto-prostaglandin F1 alpha) was detected in the culture supernatant and levels continued to rise throughout a 48-h incubation. The release of PGI2 required the continued presence of hrIL-1 alpha, did not demonstrate tachyphylaxis and was not reduced by pre-incubation with the protein synthesis inhibitors cycloheximide, tunicamycin and actinomycin or by the calmodulin antagonist trifluoroperazine. The relationship of these results to ultraviolet radiation induced erythema is discussed.     

Up-regulation of cellular FLICE-inhibitory protein in peripheral blood B lymphocytes in patients with systemic lupus erythematosus is associated with clinical characteristics

Background  Systemic lupus erythematosus (SLE) is an autoimmune disease which is involved in T- and B-lymphocyte–mediated autoimmunity. Apoptosis contributes to the maintenance of lymphocytes homeostasis and the deletion of autoreactive cells in SLE. Although there is evidence that cellular FLICE-inhibitory protein (c-FLIP), an antiapoptosis protein, is increased in human lupus T cells to keep them from apoptosis, but the expression of apoptosis-regulatory protein c-FLIP in SLE B lymphocytes remains unknown.
Aims  To study the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients and to investigate the relationship among the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients, clinical manifestation and the levels of interleukin-4 (IL-4) and IL-10.
Methods  In this study, we detected the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients by flow cytometry and the levels of IL-4 and IL-10 in SLE serum samples by enzyme-linked immunosorbent assay and analysed their relationship with clinical characteristics.
Results  We observed a significantly higher percentage of c-FLIP in peripheral B cells in SLE patients with active disease when compared to inactive ones and healthy controls. And the expression of c-FLIP in lupus peripheral B cells showed positive correlations with SLEDAI, erythrocyte sedimentation rate, C-reactive protein, antinucleosome antibody titre, IL-4, and IL-10, and negative correlation with white blood cell count. Patients with lupus nephritis had higher levels of c-FLIP in peripheral B cells than patients without lupus nephritis.
Conclusion  Our data show that overexpression of c-FLIP is relevant to the activity and severity of SLE. Its overexpression might play a role in preventing B cell from apoptosis in SLE. The cause of c-FLIP overexpression may be due to the increase of IL-4 and IL-10 levels in SLE patients.     

系统性红斑狼疮患者血清S-100蛋白检测及其临床意义

目的:通过检测系统性红斑狼疮(SLE)患者血清S-100蛋白水平,探讨S-100蛋白与SLE的关系及其临床意义。方法:用ELISA法检测无神经系统症状的SLE活动期(ASLE)患者20例,SLE稳定期(ISLE)患者6例,有神经系统症状(排除了引起脑神经损害的其他神经精神疾病)的SLE患者(NPSLE)5例及10例健康人的血清S-100蛋白。结果:ASLE、ISLE、NPSLE患者血清S-100水平均高于对照组,其中NPSLE患者血清S-100蛋白水平明显高于其他组(P<0.01)。结论:SLE患者的血清S-100蛋白水平与SLE病情有一定的关系,血清S-100蛋白水平可能是反映或预示SLE脑神经受损的一个有效指标。