HLA-DP-Positive T Cells in Patients with Systemic Lupus Erythematosus

HLA-DP⁺ T cells in peripheral blood from 23 patients with systemic lupus erythematosus (SLE) were examined using two-colour flow cytometry analysis. A marked increase of HLA-DP⁺ T cells was observed in patients with SLE (20.5–98.7%; 59.8 ± 20.8%) in comparison to normal subjects (1.3–20.6%; 11.1 ± 7.2%), and the ratio of these cells greatly exceeded that of the HLA-DR+ T cells (6.5–49.1%; 21.5 ± 12.7%). This high frequency of HLA-DP+ T cells in patients with active SLE decreased with predonisolone therapy. When the lymphocytes from normal subjects were stimulated with PHA in vitro, HLA-DP⁺ T cells increased from 1.8 to 59.2%. Therefore, it appears that the HLA-DP antigen expression on T cells is a practical marker for monitoring changes in the proportion of activated T cells in patients with SLE during the course of therapy.     

Genetic Variants in IL‐12B and IL‐27 in the Polish Patients with Systemic Lupus Erythematosus

To investigate the potential association between IL‐12B and IL‐27 gene polymorphisms and systemic lupus erythematosus (SLE), we performed a case–control study based on the Polish population. Patients with SLE and healthy individuals were examined for ?6415 CTCTAA/GC (rs17860508) and +1188A/C (rs3212227) in IL‐12B and ?924A/G (rs153109) and 4730T/C (rs181206) in IL‐27 gene polymorphisms using the high‐resolution melting method, PCR–RFLP method and TaqMan SNP genotyping assay, respectively. An increased frequency of GC/GC genotype as well as GC allele of the IL‐12B rs17860508 was found in patients with SLE, as compared with healthy subjects (P < 0.001). We did not find differences in genotype and allele frequencies of the IL‐12B rs3212227 and IL‐27 rs153109 and rs181206 variants between patients with SLE and controls. IL‐27 haplotype rs181206C/rs153109G indicated higher risk for SLE (P = 0.002), whereas haplotype rs181206T/rs153109G indicated reduced risk for SLE (P = 0.005). The IL‐12B rs3212227 A/C polymorphism was associated with the mean value of the platelets (PLT), urea and complement C3 level. Furthermore, IL‐12B rs17860508 genetic variant showed correlation with PLT, prothrombin time, international normalized ratio and alkaline phosphatase. Our results revealed that IL‐12B rs17860508 and IL‐27 haplotype CG are genetic risk factors for SLE and that both IL‐12B rs17860508 and rs3212227 predict disease phenotype.     

系统性红斑狼疮患者的Th细胞亚群平衡失调的初步研究

为分析Th亚群平衡失调在系统性红斑狼疮 (SLE )发生发展中的变化特点 ,以ELISA法检测血清IL 10、IL 12水平 ,以细胞内细胞因子的流式细胞术检测SLE患者PBMC的不同Th细胞亚群分泌细胞因子的变化特点 ,应用三色荧光标记技术分析Th1/Th2细胞表型。结果显示 :SLE患者血清IL 10水平显著高于正常人 ,而IL 12呈低水平表达。SLE患者CD4 + IFN γ IL 10 + 细胞亚群百分率显著高于正常人 ,IFN γ+ IL 10 与IFN γ IL 10 + 细胞亚群的比值明显降低 ,IFN γ+ IL 10 + 双阳性的CD4 + T细胞亦显著增多。SLE患者的CD4 + CCR5 CCR3+ 细胞亚群百分率与正常人比较显著升高 ,CD4 + CCR5 + CCR3 细胞亚群与正常人比较 ,示发现有显著差异 ,CD4 + CCR5 + CCR3 /CD4 + CCR3+ CCR5 比值显著低于正常对照组。这些结果提示 :SLE高水平IL 10与IL 12的低水平表达呈负相关 ;患者体内分泌IL 10的Th细胞数增多 ;Th细胞表面趋化因子受体的表达提示SLE存在CCR5 CCR3+ 细胞亚群的优势活化、数量增多 ,CCR5 + CCR3 /CCR3+ CCR5 细胞比例失调 ,从而导致免疫网络平衡被破坏。     

Decreased Flow-Mediated Dilatation in Patients with Systemic Lupus Erythematosus: a Meta-analysis

Premature atherosclerosis, the hallmark of cardiovascular diseases, has been found to be a significant cause of late deaths in systemic lupus erythematosus (SLE) patients. Therefore, early identification of atherosclerosis before the overt disease is curial for the management program of SLE. Flow-mediated dilatation (FMD%) is a reliable, noninvasive, easy to use, reproducible, and pathogenically relevant index for early atherosclerosis. In recent years, a number of studies have been performed to compare the mean FMD% difference between patients with SLE and healthy controls. However, these studies have shown inconclusive or even contradictory findings. In this study, to derive a more precise comparison of FMD% difference between SLE patients and healthy controls, a meta-analysis was performed. Databases were searched to identify all available studies comparing FMD% between SLE patients and healthy controls. The study eligibility criteria were cohort or case–control studies with data on both patients diagnosed with SLE and healthy controls, and use of high-resolution ultrasonography to detect FMD. Random effect meta-analysis was conducted to evaluate the overall mean FMD% difference between the two groups. Publication bias was detected by funnel plot and Egger’s test. Meta-regression analysis was performed to investigate the potential influencing factors on FMD% difference. Of the 434 articles initially identified, 22 were finally included in the meta-analysis. Compared to healthy controls, SLE patients had significantly lower FMD% (standardized mean difference, ?1.19; 95 % CI, ?1.63, ?0.74; P?I ²?=?94.3 %, P?P?=?0.006). However, after the correction for potential publication bias by using the trim-and-fill method, the main results for all studies combined were still significant (P?相似文献   

Functional Property of la-Positive T Cells in Peripheral Blood from Patients with Systemic Lupus Erythematosus

Ia-positive (Ia+) T cells in peripheral blood and their functional property were examined in patients with systemic lupus erythematosus (SLE). Binding of specific monoclonal antibodies was assessed by indirect immunofluorescence. Functional study of Ia+ T cells was carried out in coculture experiments by measuring the IgG secreted into the culture supernatant. We found that the percentage of Ia+ T cells in peripheral blood from patients with SLE was raised and the rise correlated positively with serum gamma globulin and IgG level. The elevation was further increased after stimulation with DNA in vitro, indicating the presence of DNA-sensitive T cells. Functionally, Ia+ T cells acted as helper cells in spontaneous IgG synthesis of SLE B cells, and were enriched in the OKT4 subset. These results indicate that SLE T cells are activated in vivo and that the Ia+ T cells may play a crucial role in the immunoregulatory function. Accordingly, demonstration of Ia antigens on T cells by monoclonal antibody may provide a useful tool for the measurement of immunological activity in patients with SLE.     

Defects of Autologous Mixed Lymphocyte Reaction-Activated Immunoregulatory T Cells in Patients with Systemic Lupus Erythematosus

The present study was undertaken to determine the nature of the immunoregulatory T-cell defect after autologous mixed lymphocyte reaction (AMLR) activation in patients with systemic lupus erythematosus (SLE). Although AMLR was decreased in patients with SLE compared with normals, there was no difference in major proliferative cells (T4 cells and T4+JRA+ subset) in response to AMLR. Functional activity of AMLR-stimulated T4 subsets in patients with SLE and normals was examined in helper and suppressor/inducer assay, using pokeweed mitogen (PWM)-driven IgG synthesis. The T4+JRA- (helper) subset from SLE patients showed no greater activity than normals. However the T4+JRA+ (suppressor/inducer) subset from SLE patients showed decreased suppression induction compared with normals. This defect in the suppressor/inducer function was demonstrated even in patients with inactive SLR or in remission.     

SLE患者疾病活动程度与甲状腺功能的相关性研究

目的 研究SLE患者不同疾病活跃程度与甲状腺功能的关系.方法 选取41例SLE患者作为研究对象,通过疾病活动程度评估分为非活动组和活动组.选取51例来院健康体检者作为对照组.抽取研究对象静脉血5 mL,采用电化学发光法检测血清中FT3、FT4及TSH水平,分析甲状腺功能与疾病活动度的关系.结果 SLE患者FT3、FT4水平明显低于对照组(P<0.001),SLE活动组FT3、FT4水平均低于非活动组(P均<0.05),SLEDAI评分与FT3、FT4水平呈负相关(r=-0.396,P=0.01;r=-0.522,P<0.001).结论 SLE疾病活跃程度与患者甲状腺功能密切相关,随着疾病活动度增加,FT3、FT4水平显著减低,这有助于进一步研究SLE与甲状腺功能的关系.     

Antinucleosome Antibodies and Decreased Deoxyribonuclease Activity in Sera of Patients with Systemic Lupus Erythematosus

Nucleosomes are the dominant autoantigens in patients with systemic lupus erythematosus (SLE), and immune complexes involving nucleosomes are the major cause of tissue damage. The activity of DNase I, the enzyme responsible for nucleosome degradation, has been found to be decreased in patients with SLE. However, it is not known whether DNase activity is a clinically useful parameter. The aim of our study was to assess DNase activity in a prospective study of 113 patients with SLE in relation to disease activity and organ involvement. We included two control groups: 9 patients with undifferentiated connective tissue disease (UCTD) and 14 healthy individuals. DNase activity was found to be lower in patients with SLE (63.75% ± 12.1%) than in the controls (81.3% ± 9.25%) (P < 0.001). DNase activity in patients with UCTD (64.9% ± 18.2%; P = 0.854) did not differ from that in patients with SLE. Patients with SLE had higher antinucleosome antibody titers (356.3 ± 851) than the controls (1.44 ± 2.77; P < 0.01) or UCTD patients (39.9 ± 57.7; P < 0.01). In addition, samples positive for antinucleosome antibodies displayed low levels of DNase activity. Within the SLE group, the presence of renal disease had no impact on DNase activity or antinucleosome antibody titers. Also, the SLE disease activity index showed no correlation with DNase activity. In a longitudinal study of six SLE patients, DNase activity did not follow disease activity or autoantibody titers. Our results confirm that serum DNase activity is decreased in patients with SLE, but we conclude that it is not a clinically useful parameter for the prediction of flare-ups of disease or renal involvement.     

Decreased IL-4 Producing CD4 + T Cells in Patients with Active Systemic Lupus Erythematosus-relation to IL-12R Expression

The balance of interferon- &#110 (IFN- &#110 ) and/or interleukin-4 (IL-4) producing T cells and interleukin-12 receptor (IL-12R) expression on T cells were evaluated in patients with active systemic lupus erythematosus (SLE). Assessment of intracellular IFN- &#110 and/or IL-4 were conducted with cytoplasmic staining. IL-12R presenting T cells were also assessed by flowcytometry without in vitro stimulation. In SLE, the number of IFN- &#110 producing CD4 + T cells was increased, and the absolute number of IL-4 producing CD4 + T cells was significantly decreased. Although the ratio of IL-12R presenting CD4 + T cells was significantly greater, the absolute number did not increase. The ratio of IFN- &#110 /IL-4-producing CD4 + T cells correlated with the SLE disease activity index (SLEDAI) and was significantly higher among patients with lupus nephritis. Therefore, the imbalance of IFN- &#110 /IL-4 producing CD4 + T cells was due to the decrease in IL-4 producing CD4 + T cells and may play an important pathogenic role in active SLE.     

Body Image in Patients with Systemic Lupus Erythematosus

Background

Systemic lupus erythematosus (SLE), a multisystemic disease of young women may be disfiguring and affect physical and emotional health. Body image literature in SLE is scant and controversial.

Purpose

We compared body image-related quality of life in subjects with (n?=?87) and without (n?=?78) SLE and determined its correlates using the body image quality of life inventory (BIQLI).

Method

The tool was self-administered to consenting individuals. Demographic information along with disease activity and damage assessments for SLE patients were obtained. T test, chi square test, correlational, and regression analyses were used to make comparisons.

Results

Mean age (±SD) were 42.4?±?13.1 and 38.7?±?13.2?years for SLE and non-SLE subjects, respectively. Mean (±SD) BIQLI scores were significantly worse in SLE than non-SLE subjects: 19.9?±?33.2 and 41.6?±?24.8 (p?=?0.001). In SLE, BIQLI scores correlated inversely with overall damage, irreversible cutaneous damage, alopecia, and self-reported depression, and directly with age and health status.

Conclusion

Body image in SLE is poor, and effective interventions may be directed at cutaneous disease activity, damage, and depression.     

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.     

Lithium In Vitro Enhances Interleukin-2 Production by T Cells from Patients with Systemic Lupus Erythematosus

Cellular immunity is impaired in patients with systemic lupus erythematosus (SLE). A decreased production of interleukin-2 by T cells isolated from blood of patients with SLE was found. the decrease correlated with severity of the disease. It was shown that incubation in vitro of T cells with 5 mM of lithium chloride augmented interleukin-2 production. the increase in cultures of T cells from patients with SLE was higher that than in healthy individuals. It is belived that lithium increases the cytosol inositol triphosphate level and subsequently augmented impaired itra-cellular signal transduction in the T cells from patients with SLE.     

Lithium In Vitro Enhances Interleukin-2 Production by T Cells from Patients with Systemic Lupus Erythematosus

Abstract

Cellular immunity is impaired in patients with systemic lupus erythematosus (SLE). A decreased production of interleukin-2 by T cells isolated from blood of patients with SLE was found. the decrease correlated with severity of the disease. It was shown that incubation in vitro of T cells with 5 mM of lithium chloride augmented interleukin-2 production. the increase in cultures of T cells from patients with SLE was higher that than in healthy individuals. It is belived that lithium increases the cytosol inositol triphosphate level and subsequently augmented impaired itra-cellular signal transduction in the T cells from patients with SLE.     

系统性红斑狼疮患者外周血调节性T细胞、Foxp3和IL-6的表达

目的探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)患者外周血CD4 CD25 调节性T细胞(regulatory Tcells,Tregs)、Foxp3mRNA和血浆IL-6表达的意义。方法对38例SLE患者和16例正常人采用流式细胞术检测外周血CD4 CD25 Tregs百分率,RT-PCR检测Foxp3mRNA表达,ELISA法检测IL-6水平。结果①SLE活动组和非活动组的CD4 CD25 Tregs水平均显著低于正常对照组(P<0.01);②SLE活动组的Foxp3mRNA表达水平明显低于正常对照组(P<0.05);③SLE活动组和非活动组血浆的IL-6水平均显著高于正常对照组(P<0.01),而且活动组显著高于非活动组(P<0.05);④38例SLE患者的CD4 CD25 Tregs水平与SLEDAI评分呈显著性负相关(P<0.01),Foxp3mRNA水平与CD4 CD25 Tregs呈显著性正相关(P<0.01),血浆IL-6水平与SLEDAI评分之间呈显著性正相关(P<0.01),血浆IL-6水平与CD4 CD25 Tregs/CD4 细胞比值呈显著负相关(P<0.05)。结论CD4 CD25 Tregs和Foxp3以及IL-6可能在SLE的发生和发展中发挥重要作用。     

系统性红斑狼疮病人T和B淋巴细胞凋亡的观察

为了研究SLE的T、B淋巴细胞及其亚类的凋亡情况,采用碘化丙锭染色,在流式细胞仪下观察计数:22例SLE病人淋巴细胞(包括总体淋巴细胞、CD3~+、CD4~+、CD8~+T细胞和CDl9~+B细胞)凋亡率在培养0、24、48h时均较正常组有显著增高,并以CD4~+T细胞和CDl9~+B细胞在活动期SLE病人中凋亡更突出。此外,SLE病人,自身抗体产生愈多,其细胞凋亡率愈高;疾病活动度增高,凋亡率也较高。提示;SLE病人的淋巴细胞凋亡在体外加速,与其自身抗体产生有密切关系,在其发病机制中起一定的作用。     

Placental Isoferritin Levels in Pregnant Patients with Systemic Lupus Erythematosus and/or Antiphospholipid Syndrome

PROBLEM: Low serum placental isoferritin (PLF), an immunosuppressive cytokine-like protein, was found in women with underlying placento-vascular dysfunction, such as intrauterine growth retardation and preeclamptic toxemia. The possible contribution of this placental product in the assessment of pregnant patients with either systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) was investigated. METHOD OF STUDY: Seventy-five healthy pregnant women used as controls and 25 preselected pregnant patients with either SLE and/or APS were enrolled in the study. Study patients were in remission during conception and all patients agreed to give 5 ml of venous blood at midgestation. The samples were frozen and analyzed retrospectively. After delivery, pregnancy outcomes were gathered from hospital records. RESULTS: Seventeen (68%) women had uneventful pregnancies and deliveries (normal) whereas 8 (32%) showed pathologic obstetric outcomes. Mean midgestational serum PLF levels were similar in the control and normal outcome groups (87 U/ml), whereas significantly lower levels (37 U/ml) were measured in the pathologic outcome group. Using a cutoff level of 10 U/ml, 85% from the normal outcome group and 15% from the pathologic outcome group were above this threshold level, with 60% specificity and 100% sensitivity. CONCLUSIONS: These preliminary data suggest that PLF values may reflect placento-vascular functions. These may represent a predictive biomarker for developing obstetric complications in pregnant women with either SLE and/or APS.     

SLE患者T细胞TCR/CD3复合物介导的信号转导研究

为证明SLE患者T细胞功能异常是否与其生物化学信号转导异常有关。用CD3单抗与羊抗鼠二抗IgG相交联刺激T细胞并用Thapsigargin和EGTA干预后 ,用分别粘附细胞仪连续观察 10minT细胞 [Ca2 + ]i的变化 ,并评价 [Ca2 + ]i反应与CD3分子、InsP3 生成量和患者临床特征的相关性。结果显示 :正常人和SLE患者T细胞 [Ca2 + ]i反应的基准值相似 (P =0 10 5 ) ;SLE患者高峰值、平台值T细胞的 [Ca2 + ]i反应明显高于正常对照 (P <0 0 0 1,P <0 0 0 1) ;加入Thapsigargin后二者 [Ca2 + ]i反应无显著差异 ,而加入EGTA后二者 [Ca2 + ]i反应有显著差异 ;二者的T细胞CD3阳性率和InsP3 生成量无差异 (P =0 6 6 5 ,P =0 5 37) ;且 [Ca2 + ]i异常反应与患者的疾病活动性无关。这些结果提示 :SLE患者T细胞TCR/CD3介导的信号转导途径存在异常 ;SLE患者T细胞功能异常可能是因细胞内生物化学信号途径异常所致。     

系统性红斑狼疮病人环孢素A受体mRNA的表达

目的探讨静止期、活动期系统性红斑狼疮病人(SLE)外周血单个核细胞(PBMC)环孢素A受体(CyP) mRNA表达及糖皮质激素对其表达的影响,为临床应用环孢素A辅助治疗该病提供理论依据.方法采用逆转录PCR方法,经凝胶图像半定量分析,检测患者外周血单个核细胞CyP mRNA的表达.结果 SLE病人外周血单个核细胞存在有CyP mRNA的表达,静止期较正常人差异无显著性(p>0.05)意义,但在活动期CyP mRNA的表达较正常人和静止期病人明显降低(p<0.01),地塞米松处理后,活动期病人CyP mRNA的表达水平显著上升(p<0.01).结论 SLE病人有CyP mRNA的表达,但活动期明显下降,糖皮质激素可改善CyP mRNA的表达.