趋化因子CXCL13在系统性红斑狼疮患者的血浆表达水平及临床意义

目的 检测系统性红斑狼疮(SLE)患者血浆趋化因子CXCL13表达,分析CXCL13表达与SLE疾病活动性及脏器受累的关系,探讨CXCL13在SLE发病机制中的可能作用.方法 酶联免疫吸附法(ELISA)检测60例SLE患者血浆CXCL13水平,并与21名健康体检者对照.组间计量资料比较采用Mann-Whitney检验,组间计量资料相关性分析采用Pearson相关性分析.结果 血浆趋化因子CXCLl3在SLE患者组表达水平明显高于健康对照组[(501±446)和(102±121) pg/ml,P＜0.01].有肾脏及中枢神经系统受累的SLE患者较无相应器官受累的SLE患者有着较高水平的血浆CXCL13表达(P=0.038,0.026).另外,分析发现血浆CXCL13表达水平与SLE疾病活动指数呈正相关(r=0.585,P=0.001).结论 趋化因子CXCL13在SLE发病机制中具有重要作用,可能参与了SLE肾脏及中枢神经系统受累过程;CXCL13可作为判断SLE病情活动性的指标.     

系统性红斑狼疮患者血清中可溶性人类白细胞抗原-G表达水平的研究

目的 探讨血清可溶性人类白细胞抗原(HLA)-G(sHLA-G)在系统性红斑狼疮(SLE)患者中表达水平及与疾病活动度相关性.方法 采用酶联免疫吸附试验(ELISA)方法检测58例SLE患者与60名健康人血清sHLA-G水平.结果 SLE患者血清sHLA-G水平(120±92)ng/ml显著高于健康对照组(35±33)ng/ml(P＜0.01);SLE活动期组血清sHLA-G水平(170±70)ns/mJ显著高于SLE缓解期组血清sHLA-G水平(95±88)ng/ml(P＜0.01);血清sHLA-G水平与SLEDAI呈正相关(r=0.30,P=0.01);与抗双链DNA(dsDNA)、C3、C4及抗核抗体滴度无显著相关性(P＞0.05).结论 SLE患者血清中sHLA-G表达增高,且与疾病活动度呈正相关,sHLA-G在SLE疾病发生、发展中可能发挥了一定的作用.     

系统性红斑狼疮患者血浆单核细胞化学吸引蛋白-1检测及其临床意义

目的 分析血浆单核细胞化学吸引蛋白-1(MCP-1)水平与系统性红斑狼疮(SLE)脏器受累及病情严重性的关系,探讨检测血浆MCP-1水平的临床意义.方法 采用酶联免疫吸附试验(ELISA)法检测95例SLE患者血浆MCP-1水平,并与21名健康体检者对照.结果 血浆MCP-1水平在SLE患者为(849±289)pg/ml,显著高于健康对照组的(426±266)pg/ml(P<0.01);在SLE患者,血浆MCP-1水平在有狼疮肾炎(LN)者明显高于无LN患者(P<0.01),并发狼疮脑病的患者也明显高于无中枢神经系统损害的患者(P相似文献   

系统性红斑狼疮趋化因子CXCL13水平升高的临床意义

目的 探讨趋化因子CXCL13在系统性红斑狼疮(systemic lupus erythematosus,SLE患者血浆中的表达及临床意义。方法 收集SLE患者60例,健康对照20例,采用酶联免疫吸附法(ELISA)检测两组血浆中CXCL13的表达水平,并分析与SLE患者实验室指标及疾病活动度的关系;同时比较血浆CXCL13水平在狼疮性肾炎(lupus nephritis,LN)和非LN患者间的表达差异;受试者工作特征曲线(ROC曲线)判断血浆CXCL13对诊断LN的敏感性和特异性。采用t检验、Kruskal-Wallis H检验、Pearson相关分析进行统计学数据分析。结果 SLE患者血浆CXCL13为(272. 1±232. 7) pg/ml,明显高于健康对照组(52. 1±31. 0) pg/ml (P 0. 05)。LN患者血浆CXCL13水平为(340. 9±248. 6) pg/ml,明显高于非LN患者[(134. 5±106. 9) pg/ml; Z=3. 895,P 0. 01]。血浆CXCL13水平与SLE患者SLEDAI评分呈正相关(r=0. 267,P 0. 05),与补体C3 (r=-0. 294,P 0. 05)、外周血血红蛋白含量(r=-0. 299,P 0. 05)、血小板计数(r=-0. 300,P 0. 05)、淋巴细胞计数(r=-0. 309,P 0. 05)呈负相关。疾病活动组患者血浆CXCL13水平明显高于疾病稳定组[(335. 7±248. 2) pg/ml比(144. 9±127. 5) pg/ml,t=3. 223,P 0. 01]。抗ds DNA抗体阳性组血浆CXCL13水平明显高于抗ds DNA抗体阴性组[(367. 0±285. 4) pg/ml比(204. 3±158. 6) pg/ml,t=2. 824,P 0. 01]; AHA阳性组血浆CXCL13水平明显高于AHA阴性组[(375. 3±276. 8) pg/ml比(216. 5±186. 3) pg/ml; t=2. 645,P 0. 05]。LN患者血浆CXCL13水平与血清尿素氮呈正相关(r=0. 425,P 0. 01),与e GFR呈负相关(r=-0. 385,P 0. 05)。血浆CXCL13水平≥116. 95 pg/ml,对LN诊断的敏感性为92. 5%,特异性为60. 0%。结论 SLE患者血浆CXCL13水平明显升高,可能与自身抗体产生及血液系统和肾脏系统损害有关,CXCL13可作为判断SLE疾病活动性的指标之一。     

系统性红斑狼疮患者血清IgE水平及其与疾病活动性的关系

目的评估系统性红斑狼疮(systemic lupus erythematosus, SLE)患者血清总IgE水平,并探讨其与SLE患者临床特征、实验室指标和疾病活动度的关系。方法检测SLE患者、健康对照和过敏性疾病患者血清总IgE水平。评估SLE患者临床症状和组织受累情况,采用SLE疾病活动度指数(SLE disease activity index 2000, SLEDAI 2K)评估疾病活动度。结果 SLE患者血清总IgE(中位数44.2 U/ml,范围1.82～2 630 U/ml)高于健康对照者(中位数35.65 U/ml,范围4.66～1 130 U/ml,P=0.028),但低于过敏患者(中位数350.6 U/ml,范围72.16～2 851 U/ml,P0.001)。SLE患者中活动期患者总IgE(中位数208 U/ml,范围8.18～2 510 U/ml)显著高于静止期患者(中位数26.05 U/ml,范围1.82～2 630 U/ml,P0.001);总IgE水平与SLE疾病活动度相关(r=0.51,P0.001)。SLE患者IgE水平升高与是否合并过敏性疾病无关。结论 SLE患者血清IgE水平升高,其升高与疾病活动度相关,与是否合并过敏性疾病无关。IgE可能在SLE发病中,尤其疾病活动阶段发挥免疫调节作用。     

系统性红斑狼疮患者血浆骨桥蛋白水平与疾病活动性及脏器损害的相关性研究

目的 检测系统性红斑狼疮(SLE)患者血浆中骨桥蛋白(OPN)的水平,分析其与SLE活动性及脏器损害间的关系.方法 选择68例SLE患者和36名健康体检者,采用酶联免疫吸附试验(ELISA)检测其血浆中的OPN水平.记录采血时患者的系统性红斑狼疮疾病活动指数(SLEDAI)、实验室指标等.结果 SLE患者OPN血浆水平明显高于正常对照组[(4.5±2.0)ng/ml与(1.6±0.7)ng/ml,P＜0.01 ].SLE疾病活动组高于非活动组[(5.3±2.0)ng/ml与(3.4±1.3)ng/ml,P＜0.01];SLE患者伴有肾脏损害组高于无肾脏损害组[(5.8±2.1)ng/ml与(3.5±1.3)ng/ml,P＜0.01],有肺间质病变、胃肠道病变和心包炎的高于无脏器损害[(4.8±1.2)、(6.3±1.4)、(5.4±2.6)ng/ml与(3.5+1.3)ng/ml,P＜0.05],抗心磷脂抗体阳性患者OPN水平高于抗心磷脂抗体阴性患者[(5.3±2.4)ng/ml与(4.2±1.7)ng/ml,P＜0.05].OPN血浆水平与SLEDAI呈正相关(r=0.523,P＜0.01),与尿蛋白定量(24 h)呈正相关r=0.403,P=0.001),与补体C3呈负相关r=-0.398,P=0.001),与红细胞沉降率(ESR)、抗dsDNA抗体、抗Sm抗体、IgG、IgA、IgM、球蛋白及关节炎等无相关性(P＞0.05) .结论 OPN可能参与SLE的发病,临床上可作为疾病活动及脏器损伤的观察指标.     

系统性红斑狼疮患者外周血白细胞介素-17与辅助T细胞17的检测及其意义

目的 研究系统性红斑狼疮(SLE)患者外周血白细胞介素(IL)-17蛋白和mRNA水平、辅助T细胞(Th17)细胞表达比例,探讨其临床意义.方法 用酶联免疫吸附试验检测SLE患者及对照者血浆中IL-17的蛋白水平;采用实时荧光定量反转录-聚合酶链式反应(RT-PCR)检测2组外周血中IL-17 mRNA表达水平;运用流式细胞术检测SLE患者外周血单个核细胞(PBMCs)中Th17细胞比例,进一步分析IL-17/Th17细胞与SLE临床实验室指标的相关性.计量资料组间比较采用t检验,相关性分析采用Spearman秩和相关分析.结果 SLE组患者血浆IL-17含量明显高于健康对照组,SLE组患者外周血IL-17 mRNA表达水平[(28.3±11.7)×10-5]高于对照组[(9.8±2.2)×10-5](P均＜0.01).SLE患者PBMCs中Th17细胞比例(2.5±1.5)%及IL-17荧光强度(1937±1022)显著高于对照组[(1.5±0.7)%,(1245±413)],且SLE活动期患者Th17细胞百分比高于非活动组,SLE肾病组Th17细胞比例较无肾病组明显升高(P均＜0.05).SLE患者血浆IL-17水平、Th17细胞数与SLE疾病活动性指数(SLEDAI)呈正相关(r=0.681,P＜0.01;r=0.426,P=0.034).结论 SLE患者体内IL-17蛋白分泌及基因表达水平存在明显异常,外周血Th17细胞比例亦显著升高,且与疾病活动性有明显相关,提示IL-17/Th17细胞可能在SLE发病中起着重要作用.     

系统性红斑狼疮患者血清卵泡抑素样蛋白1表达水平及其临床意义

目的 检测系统性红斑狼疮(SLE)患者血清中卵泡抑素样蛋白1(FSTL1)的水平及FSTL1在狼疮肾炎肾脏组织中的表达,探讨其在SLE疾病中的临床意义.方法 酶联免疫吸附试验(ELISA)法检测54例SLE患者及27名健康对照组血清FSTL1水平.免疫组织化学染色检测狼疮肾炎患者肾脏组织及健康者肾脏组织中FSTL1的表达情况.采用Mann-WhitneyU/检验、t检验、X2检验及Pearson检验进行统计分析.结果 SLE组FSTL1血清水平(26±21) μg/L显著高于健康对照组(12±14) μg/L(P＜0.01);SLE高血压组明显高于非高血压组(P＜0.01);SLE病程≥5年组与病程＜5年组之间差异有统计学意义(P＜0.01);血清FSTL1表达水平与SLE疾病活动指数(SLEDAI)评分(r=0.319,P=0.022)、年龄(r=0.700,P＜0.01)、病程(r=0.513,P＜0.01)、补体C4 (r=0.443,P=0.004)、总胆固醇(r=0.460,P=0.001)呈正相关;与血小板计数(r=-0.422,P=0.001)、抗双链DNA(dsDNA)抗体水平(r=--0.276,P=0.046)呈负相关.FSTL1主要表达在肾小管上皮细胞胞质内.结论 FSTL1在SLE患者血清中明显升高,且与疾病活动性有关.提示FSTL1在SLE发病机制中起一定作用.     

系统性红斑狼疮患者热休克蛋白90和白细胞介素18的表达及意义

目的:研究系统性红斑狼疮(SLE)患者热休克蛋白90(HSP90)和血浆白细胞介素18(IL-18)的表达水平及与疾病活动的关系。方法:运用Westernblot技术检测SLE患者外周血单个核细胞HSP90的表达,ELISA方法检测血浆中的IL-18水平,并与SLE疾病活动指数(SLEDAI)进行相关性分析。结果:⑴SLE患者HSP90的表达水平在活动期组(0.82±0.10)和稳定期组(0.54±0.09)与正常对照组(0.37±0.11)比较均具有显著性差异(分别P<0.01),且活动期组较稳定期组增高更明显(P<0.01);⑵SLE患者血浆IL-18水平在稳定期组(327.82±101.45pg/ml)和活动期组(459.79±134.08pg/ml)均显著高于正常对照组(252.32±76.45pg/ml)(分别为P<0.05,P<0.01);⑶SLE患者的HSP90和IL-18水平与SLEDAI评分之间呈正相关(分别为r=0.80,P<0.01;r=0.49,P<0.01)。结论:SLE患者外周血单个核细胞HSP90和血浆IL-18水平均显著增高,并且与SLE的病情活动密切相关,可能在SLE的发病机制中发挥重要作用。     

系统性红斑狼疮患者血浆IL-17和IL-23的表达及意义

目的探讨IL-17和IL-23在系统性红斑狼疮(SLE)患者血浆中的表达水平及其临床意义。方法收集诊断明确的SLE患者33例,根据SLE疾病活动指数(SLEDAI)评分随机分为活动组和非活动组,根据肾脏受累与否分为肾炎组和非肾炎组,以性别和年龄相匹配的28例健康体检者作为对照组,采用ELISA法检测血浆中IL-17和IL-23的表达水平。结果活动组患者血浆IL-17和IL-23水平明显高于对照组(P均<0.01),亦高于非活动组(P<0.05或<0.01),但二者在SLE非活动组与对照组间及肾炎组与非肾炎组间差异无统计学意义;SLE患者血浆IL-17和IL-23水平与SLEDAI评分呈正相关(r分别为0.39、0.60,P<0.05或<0.01)。结论 IL-17和IL-23在活动期SLE患者血浆中表达明显增高,二者可能参与了SLE疾病的病理过程,且与疾病的活动性关系密切。     

Adrenomedullin--a potential disease activity marker and suppressor of nephritis activity in systemic lupus erythematosus

OBJECTIVES: To investigate whether plasma adrenomedullin (AM) level is elevated in lupus nephritis and to examine if plasma AM level is correlated with systemic lupus erythematosus (SLE) disease activity and severity of lupus nephritis after multivariate adjustment. METHODS: Consecutive SLE patients and healthy volunteers of age >/=16 were recruited from the rheumatology clinics of two hospitals in Hong Kong. SLE patients with nephritis fulfilled the American College of Rheumatology criteria for renal involvement and had percutaneous renal biopsy performed. Subjects were divided into three groups: (i) SLE patients with nephritis, (ii) SLE patients without nephritis and (iii) normal controls. The demographic and clinical variables were compared between these groups of patients and plasma AM level was determined by radioimmunoassay. Factors associated with plasma AM level were explored by regression analysis with adjustment of confounding factors. RESULTS: Sixty SLE patients (39 with nephritis and 21 without) and 23 normal subjects were studied. The plasma AM level of SLE patients was significantly higher than that of normal controls. SLE patients with nephritis had significantly higher plasma AM level than those without nephritis and normal controls (P<0.001). In regression analysis, proteinuria was negatively associated with plasma AM level (P=0.006) whereas SLE disease activity index was positively associated with plasma AM level after multivariate adjustment (P=0.002). CONCLUSIONS: Plasma AM is elevated in lupus nephritis, which correlates with lupus disease activity. It is negatively associated with urine protein excretion although it is unrelated to the type of renal pathology per se. Plasma AM may play a role to suppress the activity of lupus nephritis.     

Neuronal and astrocytic damage in systemic lupus erythematosus patients with central nervous system involvement

OBJECTIVE: Symptoms originating from the central nervous system (CNS) frequently occur in patients with systemic lupus erythematosus (SLE). CNS involvement in lupus is associated with increased morbidity and mortality. Currently, reliable markers for activity in this condition are absent. The goal of this study was to determine the level of the light subunit of the neurofilament triplet protein (NFL) and that of glial fibrillary acidic protein (GFAP) in the cerebrospinal fluid of SLE patients with clinically verified CNS involvement and compare them with the levels in SLE patients without CNS involvement. METHODS: We assessed cerebrospinal fluid obtained from 99 patients with SLE and 99 age-matched controls for the presence of soluble molecules indicating neuronal destruction and astrogliosis-NFL and GFAP, respectively. Patients were evaluated clinically, with magnetic resonance imaging (MRI) of the brain, cerebrospinal fluid analyses, and neuropsychiatric tests. RESULTS: In the group of lupus patients with CNS involvement, intrathecal levels of NFL and GFAP were increased an average of 7-fold (P 相似文献   

Cerebrospinal fluid and serum prolactin in systemic lupus erythematosus with and without central nervous system involvement

Aim: Recent research has shown that prolactin (PRL) may participate in the pathogenesis of systemic lupus erythematosus (SLE), and hyperprolactinemia may be related to disease activity. The current study investigated both serum and cerebrospinal fluid (CSF) PRL in SLE patients and their possible relationship to central nervous system (CNS) involvement. Methods: Prolactin levels were determined by immunoradiometric assay. Serum PRL levels were detected in 80 patients with SLE and 25 matched healthy controls. Disease activity was scored by SLEDAI. CSF PRL levels were detected in 7 cases of CNS‐involved SLE, eight cases of non‐CNS‐involved inactive SLE and eight cases of non‐SLE CNS disorders. Results: Hyperprolactinemia was present in 40% of SLE patients. Serum PRL levels were significantly correlated with SLEDAI scores. There was no significant difference of serum PRL levels between SLE patients with or without CNS involvement, but the mean CSF PRL levels were higher in CNS‐involved SLE patients than in non‐CNS‐involved SLE and non‐SLE patients. There was no significant correlation between serum and CSF PRL levels. Conclusions: Our results suggest that high serum PRL levels correlate with active disease in SLE, but not with CNS involvement. CSF PRL levels in SLE patients correlate with CNS involvement, which indicates that CSF PRL may be involved in the pathogenesis of CNS‐SLE.     

干扰素诱导蛋白44基因与系统性红斑狼疮的相关性研究

目的 探讨系统性红斑狼疮(SLE)患者外周血白细胞干扰素诱导蛋白 44(IFI44)基因实时定量表达水平与SLE临床表现及病情活动的相关性.方法 收集100例SLE患者,40例非SLE其他自身免疫性疾病患者,40名健康对照人群的临床资料,抽提外周血总RNA并逆转录成eDNA,运用SYBRgreen dve Ⅰ实时定量聚合酶链反应(RT-PCR)检测患者和对照组的IFI44基因定量表达水平,并对其与各临床指标及病情活动度的相关性进行分析.数据分析采用方差分析,采用Pearson及Spearman检验进行相关性分析.结果 ①SLE患者组的IFI44拷贝数26.8±5.3明显高于非SLE组7.4±2.7(P=0.0012)和健康对照组5.2±2.0(P=0.005);而非SLE患者组与健康对照组差异无统计学意义.②SLE重度活动组患者IFI44表达量63.1±22.4明显高于非活动组9.2±1.8(P=0.000)和轻度活动组患者28.0±7.2(P=0.015).③SLE患者组的IFI44拷贝数与SLEDAI积分之间呈正相关(r=0.38,P=0.000),与尿蛋白定量(24 h)也呈正相关(r=0.42,P=0.000).结论 IFI44基因在SLE患者中有明显表达上调现象;检测IFI44的表达水平有助于判断SLE患者病情活动状况.

Abstract：

Objective To investigate the expression of interferon-induced protein 44 (IFI44) gene in the leukocytes of the peripheral blood samples from patients with systemic lupus erythematosus (SLE), and to evaluate the relationship between the expression level and disease activity. Methods Mononuclear cells in the peripheral blood samples from 100 SLE patients were compared with those of 40 disease controls and 40 healthy donors (HD) and the expression of the IFI44 was evaluated by quantitative real-time PCR.Comparisons between groups were performed with ANOVA, and the correlation analysis between the level of expression was higher in SLE patients than disease controls and healthy donors (26.8±5.3, 7.4±2.7, 5.2±2.0,respectively) (P=0.0012, P=0.005), but no difference was found between disease controls and healthy donors. Mild disease activity and the SLE patients with stable disease (63.1±22.4, 28.0±7.2, 9.2±1.8, respectively)and 24 hours urine protein level (r=0.42, P=0.000). Conclusion IFI44 is demonstrated to be highly expressed in SLE patients. The level of IFI44 may be a promising candidate biomarker for identifying SLE activity.     

Altered levels of adipocytokines in association with insulin resistance in patients with systemic lupus erythematosus

OBJECTIVE: The metabolic syndrome, closely associated with cardiovascular disease, is characterized by increased insulin resistance (IR). Although accelerated atherosclerosis is frequently observed in systemic lupus erythematosus (SLE), the prevalence and significance of IR remain to be elucidated. We evaluated IR in association with plasma concentrations of adipocytokines in patients with SLE. METHODS: Outpatients with SLE (n = 37) and healthy controls (n = 80) were studied. A value of the homeostasis model assessment index (HOMA-IR) > 2.0 was considered to be IR. Plasma concentrations of adiponectin and tumor necrosis factor-a (TNF-a) were measured by ELISA and leptin by radioimmunoassay. RESULTS: HOMA-IR indices of the SLE patients were significantly higher than those of controls (2.3 +/- 2.3 vs 1.3 +/- 1.0, respectively; p < 0.01), although both groups exhibited a similar body mass index. The prevalence of hypertension and diabetes mellitus was significantly higher in patients with SLE compared with controls (48.6% vs 8.8% and 10.8% vs 0%). Twelve SLE patients (32%) with IR exhibited significantly higher incidence of hypertension and current proteinuria than SLE patients without IR. Plasma leptin, TNF-a, and, unexpectedly, adiponectin levels were higher in SLE patients than controls (adiponectin, 13.7 +/- 5.0 vs 9.5 +/- 3.9 microg/ml). Among the SLE patients, patients with IR showed significantly lower adiponectin levels than patients without IR (10.9 +/- 4.6 vs 15.4 +/- 4.4 microg/ml). Serum levels of adiponectin were significantly correlated inversely with HOMA-IR in SLE patients. CONCLUSIONS: Elevated levels of adiponectin in SLE, despite inverse correlation with IR, suggest the possible involvement of adiponectin in IR and alterations in its effect on insulin sensitivity.     

Elevated plasma concentrations of nitric oxide,soluble thrombomodulin and soluble vascular cell adhesion molecule-1 in patients with systemic lupus erythematosus

OBJECTIVE: To investigate the correlations among plasma concentrations of nitric oxide (NO), soluble thrombomodulin (sTM) and vascular cell adhesion molecule (sVCAM-1), and whether these three molecules are associated with renal involvement in patients with systemic lupus erythematosus (SLE). METHODS: Plasma NO concentrations of 73 SLE patients (35 with renal disease, RSLE patients; 38 without renal disease, SLE patients) and 28 age- and sex-matched healthy control subjects were measured by the non-enzymatic Griess assay, and sTM and sVCAM-1 by enzyme-linked immunosorbent assay. RESULTS: In RSLE patients, plasma nitrite concentrations were significantly higher than in control subjects (P=0.009) and correlated positively with plasma sTM, plasma creatinine and urea (all P<0.05). Plasma sTM and sVCAM-1 concentrations were significantly elevated in RSLE and SLE patients (both P<0.0001) compared with controls. Plasma sTM was significantly correlated with plasma sVCAM-1, and both were correlated with plasma creatinine and urea and the SLE Disease Activity Index (all P<0.05). CONCLUSION: Elevated plasma NO, sTM, and sVCAM-1 concentrations have significant intercorrelations and are strongly associated with renal involvement in SLE.