CD40在系统性红斑狼疮外周血淋巴细胞的表达

使用密度离心法分离SLE患者和正常人外周血单个核细胞 (PBMC ) ,采用流式细胞术检测B淋巴细胞白细胞分化抗原 4 0 (CD4 0 )的表达水平 ,进行SLE患者 (活动期和缓解期 )和正常人之间的比较 ;并进行B淋巴细胞CD4 0表达水平和血清抗dsDNA抗体水平及狼疮活动指数 (SLEDAI)的相关分析。结果表明 ,活动期SLE患者外周血B淋巴细胞比例 (% )和其表达CD4 0的比例 (% )均明显高于缓解期SLE患者和对照组 ,其表达CD4 0的平均荧光强度 (MFI)在活动期SLE患者最高 ,缓解期SLE患者稍低 ,对照组最低 ;相关分析结果表明 ,活动期SLE患者B淋巴细胞CD4 0的表达比例 (% )和强度 (MFI)均与血清抗dsDNA抗体及SLEDAI呈正相关 ,后两者呈高度相关 ;缓解期SLE患者B淋巴细胞表达CD4 0的强度 (MFI)和SLEDAI呈正相关。CD4 0在活动期SLE患者B淋巴细胞的表达增加 ,其水平与疾病活动度有关。     

Expression of CTLA-4 Molecule in Peripheral Blood T Lymphocytes from Patients with Systemic Lupus Erythematosus

CTLA-4 is a cell surface molecule expressed on activated T cells that is suggested to deliver a negative signal for T cell activation. Since CTLA-4 might be a negative regulator of autoimmune diseases, we investigated its expression on T cells from 20 patients with systemic lupus erythematosus (SLE) by flow cytometric analysis and RT-PCR. We found that although CTLA-4 mRNA was readily detected in all patients and controls, only a very minor subset of T cells expressed detectable surface CTLA-4 molecules in both groups. But patients with SLE had significantly increased percentages of CTLA-4-positive T cells compared with normal controls, implying at least that there was no apparent defective expression of CTLA-4 molecule in human lupus. The kinetics of CTLA-4 expression on T cells stimulated in vitro with PMA plus ionomycin were similar in normal controls and patients with SLE. The expression of CTLA-4 molecules after stimulation increased gradually and peaked at 72 hr. However, the induction of CTLA-4 expression on patients' T cells appeared to be weaker than that of normal individuals. Whether this reflects impaired down regulation by CTLA-4 molecules in SLE patients needs to be clarified further.     

Mitogenic Responses to Lipopolysaccharide by B Lymphocytes from Patients with Systemic Lupus Erythematosus

Peripheral blood lymphocytes from 43 patients with systemic lupus erythcmatosus (SLE) and from age- and sex-matched normal controls were cultured with lipopolysaccharide (LPS) to examine the response to the polyclonal B-cell activator. Lymphocytes from active SLE patients incorporated 4840±471 (mean ± SE) cpm in response to LPS, whereas lymphocytes from inactive SLE patients incorporated 6906 ± 897 cpm. In contrast, lymphocytes from normal individuals incorporated 7452 ± 1126 cpm. Ig synthesis of lymphocytes from active SLE in response to LPS stimulation was also less than that of normal individuals. The helper T-cell function of active SLE, as examined by co-culturing irradiated SLE lymphocytes with unirradiated normal lymphocytes, was normal. These results thus suggested that a defect of B lymphocytes exists in active SLE patients. This B-cell defect and T suppressor cells apparently play an important role in the pathogenous of SLE.     

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B淋巴细胞PD-L1的表达

目的 探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)患者外周血B淋巴细胞PD-L1的表达及其在SLE发病中的意义.方法 应用免疫荧光标记和流式细胞仪技术检测SLE患者外周血B淋巴细胞上PD-L1的表达水平.结果 活动期SLE患者外周血B淋巴细胞CD19 、CD19 /PD-L1 的表达水平明显高于SLE非活动期患者(P＜0.05)和正常对照组(P＜0.05).结论 活动期SLE患者B淋巴细胞的PD-L1表达异常增加,其可能在SLE发病机制中起重要作用.     

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。     

Activation Profile of Intracellular Mitogen-Activated Protein Kinases in Peripheral Lymphocytes of Patients with Systemic Lupus Erythematosus

Introduction  

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with aberrant activation of T and B lymphocytes. Abnormal activation of intracellular signaling molecules in lymphocytes by inflammatory cytokines can instigate the inflammation in SLE.     

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.     

Expression of CD80 and CD86 on Peripheral Blood T Lymphocytes in Patients with Systemic Lupus Erythematosus

CD80 and CD86 were detected in high amounts on circulating T cells in the peripheral blood of some patients with systemic lupus erythematosus (SLE), using flow cytometry and monoclonal antibodies. Patients with other connective tissue diseases did not have a high percentage of T cells expressing CD80 or CD86 in their peripheral blood. CD80 was expressed mainly on CD4 T cells, whereas CD86 was expressed on CD8 T cells, and these two populations were associated with paticular clinical features. These two molecules were expressed on different T-cell populations and might have different roles in the generation and regulation of immune responses. Since high expression of CD86 on T cells was detected much earlier than the appearance of clinical features and a high titer of anti-DNA antibody, it may be a useful parameter for predicting the flare of SLE.     

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CyPmRNA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CyPmRNA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CyPmRNA的表达水平显著上升（P＜0．01）。结论 SLE病人有CyPmRNA的表达,但活动期明显下降,糖皮质激素可改善CyP mRNA的表达。     

Changes in Apoptotic Gene Expression in Lymphocytes from Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients Compared with Healthy Lymphocytes

Introduction

Systemic lupus erythematosus (SLE) and rheumatoid arthritis have complex genetic traits, but in both autoimmune diseases, dysfunctional apoptosis appears to play a part in disease pathology. This study examined the levels of in vitro apoptosis in lymphocytes from healthy, rheumatoid arthritis (RA) and SLE individuals and related observed differences to their lymphocyte apoptosis gene profiles.

Materials and Methods

Lymphocytes were assessed for cell death by nuclear pyknosis and DNA fragmentation. Control, SLE and RA apoptosis gene profiles were obtained by quantitative real-time polymerase chain reaction (QRT-PCR) analysis.

Results and Discussion

The mean levels of pyknosis in RA and SLE freshly isolated lymphocytes were significantly higher than in control lymphocytes. Ninety-three apoptosis genes were analysed by QRT-PCR of mRNA from RA, SLE and healthy lymphocytes. We identified significant differences (p?<?0.05) in the expression of the same 11 of 93 and two of 93 apoptotic genes in individual SLE and RA patients tested as compared with controls.

Conclusion

We propose that similarly altered expression of specific apoptotic regulatory genes (e.g., the death effector domain-containing DNA-binding protein and apoptosis-associated speck-like protein containing a CARD) occurs in the lymphocytes of individual patients with SLE or RA that may influence the extent and rate of spontaneous apoptosis in these autoimmune conditions.     

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.     

T Lymphocytes from Patients with Systemic Lupus Erythematosus Show Increased Response to Interleukin-2 after Costimulation with OKT3 Monoclonal Antibody and Phorbol Esters

In the present study we have examined the potential contribution of IL-2/IL-2R interactions in CD3-mediated responses by T lymphocytes from patients with systemic lupus erythematosus (SLE). T-cells from SLE patients showed normal IL-2 production when activated with OKT3 MAb and submitogenic concentrations of PMA, in cultures in which uptake of endogenous IL-2 was prevented by pretreatment with anti-Tac MAb. In contrast, PHA-induced IL-2 production was lower in patients under the same conditions. Under these stimulatory conditions the proportions of T-cells expressing IL-2R CD25 molecules was comparable in patients and controls. There was earlier and higher binding of exogenously added IL-2 in T lymphocytes from patients activated via the CD3 pathway. Furthermore, these cells responded to IL-2 with stronger proliferative responses than cells from control subjects. These findings may partly explain the increased proliferative responses of SLE T-cells when stimulated via the CD3 pathway.     

Degradation of Soluble Immunoglobulin Aggregates in Vitro by Monocytes from Normal Subjects and from Patients with Systemic Lupus Erythematosus

The capacity of human peripheral monocytes to degrade soluble immunoglobulin (IgG) aggregates (AIgG) was studied in vitro. Under serum-free conditions peripheral monocytes from normal donors were able to degrade soluble AIgG in a linear and time-dependent fashion. Addition of fresh human or fresh guinea-pig serum to the incubation mixtures caused a marked increase in degradation of the amount of soluble AIgG available. The stimulatory effect of fresh serum was complement-mediated, because it was abolished by heat treatment of the serum and was not seen when C4- or C3-deficient sera were tested. Functional inactivation of C3 receptors on the phagocytes by trypsin also abolished the complement-mediated stimulation, suggesting cooperation between Fc and C3 receptor in degradation of soluble AIgG. No significant differences were found between monocytes from normal donors and those from patients with systemic lupus erythematosus, as far as degradation is concerned in the presence of complement.     

系统性红斑狼疮患者心理状况调查

目的 调查SLE患者的心理状况。方法 67例SLE患者填写症状自评量表(SCL-90)及自制的SLE患者心理影响因素量表。结果 SLE患者与中国常模比较，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。结论 SLE患者心理健康状况普遍较差，提示以后在药物治疗的同时，应辅以心理治疗，为患者求得更高的生活质量。     

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.     

In Vitro Effects of Thymosin on T-Cell Subsets in Systemic Lupus Erythematosus

Abstract

The possible immunomodulatory influence of thymosin on lymphocytes from patients with active systemic lupus erythematosus (SLE) has been evaluated. Such patients have decreased numbers of T-suppressor (Tγ) cells and normal numbers of T-helper (Tμ) cells, resulting in an abnormally low Tγ/Tμ ratio. In vitro incubation of lymphocytes from active SLE patients with thymosin resulted in a normalization of the Tγ/Tμ ratio. This occurred because of a decrease in Ty cells rather than an increase in Tγ cells. The normalization of Tγ/Tμ ratios in vitro in the presence of thymosin is compatible with possible in vivo immunomodulatory effects of these peptides.     

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.     

Functional Differences of Anti-T-Cell Antibody in Patients with Systemic Lupus Erythematosus and Ulcerative Colitis

The loss of suppressor T-cell function results in an abundant production of autoantibodies in systemic lupus erythematosus (SLE). As a cause of this suppressor T-cell defect, anti-T-cell antibody seems to be of prime importance. On the other hand, anti-T-cell antibodies can be detected in various other autoimmune diseases, but their functional characteristics have not been determined. In the present study, the functional characteristics of anti-T-cell antibody from a selected subgroup of patients with ulcerative colitis (UC) were compared with those from patients with SLE. Anti-T-cell antibody from the patients with SLE reacted with a T8 subset, resulting in a suppressor defect, whereas anti-T-cell antibody from the UC patients reacted primarily with a T4 subset. Functionally, SLE- T cells failed to proliferate in response to concanavalin A, whereas UC- T cells from UC patients failed to proliferate in response to phytohaemagglutinin. In the Ig synthesis system, both SLE- and UC- T cells increased Ig production of B cells. Since UC+ T cells did not contribute to the generation of Con-A-inducible suppressor activity, we believe that serum from the selected subgroup of patients with UC reacted with the inducer T-cell subset.