系统性红斑狼疮患者外周血单个核细胞miR-125b及miR-145的表达及临床意义

目的探讨miR-125b及miR-145在系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)中的表达水平及其临床意义。方法选取海南省人民医院收治的136例SLE患者,采用SLE病情活动指数(SLEDAI)评分将其分为低活动组(n=75)和高活动组(n=61),另选取60例健康体检者作为对照组。采用实时定量PCR(RT-PCR)法检测各组PBMC中miR-125b及miR-145水平,分析其对SLE患者的诊断价值。Pearson相关分析SLE患者miR-125b及miR-145水平与抗双链DNA(dsDNA)抗体、C3、C4、IgG、血沉(ESR)、C反应蛋白(CRP)及SLEDAI评分的相关性。结果 SLE组、高活动组和低活动组抗dsDNA抗体、ESR、IgG及CRP水平均明显高于对照组(P<0.05),而C3及C4水平均明显低于对照组(P<0.05)。SLE组、高活动组和低活动组PBMC中miR-125b(0.84±0.23、0.42±0.09和1.53±0.28 vs 6.12±1.83)及miR-145(0.68±0.17、0.35±0.06和1.12±0.20 vs 2.15±0.64)表达水平均明显低于对照组(P<0.01),且高活动组PBMC中miR-125b(0.42±0.09 vs 1.53±0.28)及miR-145(0.35±0.06 vs1.12±0.20)表达水平明显低于低活动组(P<0.01)。SLE患者治疗后miR-125b(2.60±0.71 vs 0.84±0.23)及miR-145(1.96±0.58 vs 0.68±0.17)表达水平明显高于治疗前(P<0.01),SLE患者治疗后抗dsDNA抗体(96.24±17.20 vs 272.36±64.35)水平明显低于治疗前(P<0.01)。ROC曲线分析显示,miR-125b、miR-145及抗dsDNA抗体三项联合诊断SLE的AUC(95%CI)为0.928(0.871～0.986),其敏感度(90.4%)和特异度(85.0%)较好。相关分析显示,SLE患者miR-125b、miR-145与抗dsDNA抗体、IgG、SLEDAI评分均呈负相关(P<0.05),miR-125b与miR-145呈明显正相关(r=0.805,P<0.05)。结论 miR-125b及miR-145水平在SLE患者PBMC中明显降低,且与SLE病情活动相关,联合抗dsDNA抗体检测对SLE诊断具有一定价值。     

系统性红斑狼疮患者血清补体H因子水平及其意义

目的:通过检测系统性红斑狼疮(SLE)患者血清补体因子H(CFH)的表达水平,探讨其水平变化与SLE患者其他实验室检测指标关系及其在SLE发病中的作用.方法:选取符合1982年美国风湿病学会制定的SLE诊断标准的37例SLE患者,另选30例健康对照者,采取酶联免疫吸附法(ELISA)检测SLE组及对照组血清中的CFH的水平,同时检测临床相关指标,分析CFH在各组患者血中的变化及其与临床各指标的相关性.结果:SLE患者血清CFH水平为(332.96±135.27)μg/L,低于正常对照组水平[(414.81±72.79)μg/L,P<0.05].SLE血清CFH水平与补体C3呈明显正相关(r=0.518,P<0.001),与ds-DNA,尿微量白蛋白,SLEDAI评分呈负相关(r=-0.425,P<0.05;r=-0.472,P<0.05;r=-0.369,P<0.05).结论:CFH的减少可能参与SLE的发病过程,特别与SLE造成肾脏损伤有?是导致SLE患者低补体血症的因素之一,在一定程度上可反映疾病活动程度.     

系统性红斑狼疮患者外周血miR-7的表达及其意义

目的研究microRNA-7(miR-7)在系统性红斑狼疮(SLE)患者外周血的表达及其意义。方法 20例SLE患者和20例性别年龄匹配的健康对照者,荧光定量PCR检测PBMC、B细胞、T细胞和单核细胞中miR-7的表达以及靶基因PTEN的mRNA水平,通过电转染方法将miR-7的前体Pre-miRTM-miR-7 Precursor/抑制剂antimiRTM-miR-7抑制剂转染至SLE患者B细胞中,流式细胞检测B细胞增值功能。应用生物信息学方法及双荧光素酶报告基因系统预测并验证miR-7的靶基因。结果 SLE患者PBMC及B细胞中miR-7的表达显著高于健康对照(P0.01)。PTEN是miR-7的一个靶基因,转染miR-7的前体至SLE患者B细胞可抑制PTEN表达(P0.05),促进B细胞增殖(P0.05),转染miR-7抑制体则可以促进PTEN表达(P0.05),抑制B细胞增值(P0.05)。结论 miR-7参与了SLE的发病机制,调控PTEN的表达,并介导了SLE患者B细胞的增殖,是SLE潜在的治疗靶点。     

血清补体H因子在系统性红斑狼疮早发冠心病患者中的水平及意义

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种弥漫性、全身性自身免疫病,补体活化是其发病特点之一.近年来其发病人数明显增多,有流行病学研究发现SLE人群的冠心病患病率为6％ ～10％,其风险增高超过同年龄段普通人群的50倍[1].补体H因子(complete factor H,CFH)是补体系统中旁路激活途径重要的调节物质之一.     

巨细胞病毒及EB病毒感染与儿童系统性红斑狼疮疾病活动度的关系

为分析巨细胞病毒（cytomegalovirus, CMV）及EB病毒（Epstein-Barr virus, EBV）感染与儿童系统性红斑狼疮（systemic lupus erythematosus, SLE）疾病活动度的关系,选取78例SLE患儿作为SLE组,根据发病时间、使用激素和免疫抑制剂的情况将SLE患儿分为新发组（35例）和稳定组（43例）,另选取接受健康体检的100例健康儿童作为对照组,采用Spearman法分析CMV及EBV感染与儿童SLE的相关性。结果显示,SLE组患儿CMV IgM、EBV DNA阳性率分别为25.64%、26.92%,均显著高于对照组（3.00%、12.00%,P<0.05）;Spearman法相关性分析结果显示,CMV IgM、EBV DNA阳性与SLE呈显著正相关（r值分别为0.375、0.241,P<0.05）;稳定组患儿CMV IgM阳性率为34.88%,显著高于新发组（14.29%,P=0.038）;CMV IgM（+）组抗核糖体P蛋白（anti-ribosomal P protein, Rib-P）抗体阳性率（60.00%...     

不同状态下系统性红斑狼疮与补体的相关性分析

目的观察不同状态下系统性红斑狼疮(systemic lupus erythematosus,SLE)患者补体C3、C4水平变化并探讨其临床意义。方法选取326例系统性红斑狼疮患者作为本次研究对象。按照抗双链DNA(dsDNA)抗体阴阳性分为dsDNA阴性及阳性组,按照抗核抗体(ANA)核型分为阴性、均质型、斑点型、核仁型及其他型组。比较两种分组方式下C3、C4的结果。结果dsDNA阳性患者C3、C4水平均低于阴性患者,差异具有统计学意义(P<0.05);ANA为均质型、斑点型及其他型患者C3、C4水平均低于ANA阴性组及核仁型组患者,差异具有统计学意义(P<0.05)。结论不同状态下系统性红斑狼疮患者补体C3、C4水平存在差异,联合检测补体C3、C4有助于对SLE病情活动性及自身抗体类型作出判断。     

miR-92a与miR-19b对小鼠胰岛β细胞胰岛素基因表达的影响

目的:探讨微小RNA-92a(miR-92a)和微小RNA-19b(miR-19b)对小鼠胰岛β细胞胰岛素基因表达的影响。方法:qPCR检测小鼠胰岛素瘤MIN6细胞内源性miR-92a和miR-19b的相对表达水平。将MIN6细胞分为对照组及实验Ⅰ、Ⅱ组(每组n=3),分别转染阴性对照miRNA(NC)、miR-92a和miR-19b,qPCR验证miRNAs的过表达,光学显微镜观察细胞形态,CCK8法检测细胞活力,qPCR、Western blot及免疫荧光检测胰岛素表达情况,生物信息学预测、双萤光素酶报告基因实验和Western blot分析miR-92a和miR-19b调控胰岛素表达的可能机制。结果:与成体胰腺祖细胞相比,MIN6细胞内源性miR-92a和miR-19b相对表达量显著降低(P<0.05);过表达miR-92a和miR-19b对MIN6细胞活力没有影响,但抑制胰岛素mRNA和蛋白表达;miR-19b显著抑制NeuroD1 3’UTR萤光素酶活性和NeuroD1蛋白表达(P<0.05),而miR-92a对NeuroD1 3’UTR萤光素酶活性和NeuroD...     

血清IL-34 水平与SLE 疾病活动度关系的研究

目的:检测系统性红斑狼疮(Systemic lupus erythematosus,SLE)患者血清白细胞介素(Interleukin,IL)-34 水平,并进一步探讨IL-34 与临床和实验室指标及SLE 疾病活动度的关系。方法: 采用酶联免疫吸附试验(Enzyme-linked immunosorbent assay,ELISA)测定78 例SLE 组及53 名正常对照组血清IL-34 水平,SLE 组与正常组血清IL-34 水平分析采用曼-惠特尼U 检验(Mann-Whitney U test)。结果:与正常对照相比,SLE 组血清IL-34 水平明显高于正常对照组[(Median,128.9 pg/ ml) vs (Median,52.4 pg/ ml),P<0.001],差异有统计学意义。IL-34 水平与SLE 疾病活动度、双链DNA 抗体(anti-double stranded DNA antibody,anti-dsDNA)滴度、C 反应蛋白(C-reactive protein,CRP)呈正相关,与C3 水平呈负相关。结论:血清IL-34 可能成为SLE 的一血清标志物,因其在SLE 患者中升高,且与疾病活动度相关。     

系统性红斑狼疮患者血清IL-10的水平及临床意义

目的 观察系统性红斑狼疮(systemic lupus erythematosus,SLE)患者血清IL-10的表达与疾病活动的关系.方法 选取22例SLE患者及24名健康人作为对照,根据狼疮疾病活动指数(SLE disease activity index,SLEDAI)将SLE患者分为活动期组和非活动期组,检测血清抗dsDNA抗体,血清总补体溶血活性(CH50)及C反应蛋白(C reactive protein,CRP),酶联免疫吸附法(ELISA)检测血清IL-10表达.结果 与对照组[(18.11±6.97)ng/L]相比,IL-10在SLE活动期组[(78.54±5.62)ng/L,P＜0.01]及非活动期组[(30.36±10.98)ng/L,P＜0.05]均有所增高,活动期组增高更为明显(与非活动期组相比,P＜0.05).IL-10水平与SLEDAI呈正相关(SLE活动期,r=0.77,P＜0.01;SLE非活动期,r=0.84,P＜0.01),IL-10的水平与抗dsDNA抗体(r=0.71,P＜0.01)、CRP(r=0.63,P＜0.01)和CH50(r=-0.56,P＜0.05)均相关.结论 IL-10在SLE患者血清中表达升高,在疾病活动时更为明显,IL-10能反应疾病活动的程度,可以做为临床观察SLE疾病活动的指标之一.     

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.     

Serum Growth Arrest-Specific Protein 6 Levels are a Reliable Biomarker of Disease Activity in Systemic Lupus Erythematosus

Purpose

Growth arrest-specific protein 6 (Gas6) has been suggested to be a biomarker of disease activity in patients with systemic lupus erthematosus (SLE). We investigated the clinical significance of this protein in Korean SLE.

Methods

Blood samples were collected from 150 SLE patients and 50 normal controls (NC). In addition, follow-up samples were collected from 50 SLE patients.

Results

Serum Gas6 levels of SLE patients (43.01?±?28.02 ng/mL) were higher than those of NC (20.15?±?9.23 ng/mL, p?<?0.001). When evaluated sensitivity and specificity of the Gas6 for diagnosing SLE using ROC curves, the sensitivity and specificity were 72.7 % and 84 % with a cut-off value of 25.3 ng/mL. In the ROC analysis of Gas6, anti-dsDNA antibody, ESR, complement 3 and complement 4 to identify patients with active lupus, area under the curve (AUC) of Gas6 was highest with 0.763. Serum Gas6 levels were significantly higher in the patients with serositis (70.04?±?30.85 ng/mL) and renal disorder (65.66 ±32.28 ng/mL) compared to those without (41.88?±?27.44 ng/mL, p?=?0.033, 40.3?±?26.33 ng/mL, p?=?0.001, respectively). Gas6 levels were correlated positively with anti-dsDNA antibody (r?=?0.199, p?=?0.015), ESR (r?=?0.204, p?=?0.013) and SLEDAI (r?=?0.512, p?<?0.001). In addition, serum Gas6 levels were correlated negatively with hemoglobin (r?=??0.165, p?=?0.043), lymphocyte count (r?=??0.165, p?=?0.043), complement 3 (r?=??0.343, p?<?0.001) and complement 4 (r?=??0.316, p?<?0.001). Furthermore, change in serum Gas6 levels was correlated with change in SLEDAI levels in the SLE patients that were followed up (r?=?0.524, p?<?0.001).

Conclusion

These results suggest that serum Gas6 can be a reliable clinical marker for monitoring disease activity and treatment response in SLE.     

Serum Pro-hepcidin Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus

Hepcidin is a principal iron regulatory hormone and its expression is stimulated by cytokines. The aim of this study was to determine serum levels of the prohormone form of hepcidin, pro-hepcidin, in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The study included 72 RA and 28 SLE patients and 33 healthy controls (HC). Serum iron status, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and pro-hepcidin levels were determined. Pro-hepcidin levels in the RA group was higher than SLE and HC groups (p < 0.05, p < 0.001, respectively). Pro-hepcidin levels did not correlate with disease activity scores, cytokine levels and serum iron status in the RA and SLE groups, while it correlated with TNF-alpha, IL-6 and ferritin levels in the HC group (r = 0.459, p < 0.01, r = 0.374, p < 0.05, r = -0.603, p < 0.01, respectively). Pro-hepcidin levels show extremely wide variations within the groups as do iron status and cytokines. Despite these wide variations correlation analysis do not reveal anything.     

抗C1q抗体与系统性红斑狼疮患者病情活动的相关性及其临床意义

目的探讨抗C1q抗体（C1qAb）与系统性红斑狼疮（SLE）患者病情活动的相关性及其临床意义。方法用酶联免疫吸附实验（ELISA）检测98例SLE患者、108例其他风湿病患者及67例健康体检者中血清抗C1qAb,并对SLE患者的其他实验室检测结果进行统计学分析。结果SLE患者血清中抗C1qAb阳性率显著高于其他风湿病及健康体检者（P〈0．05）;其中,抗C1qAb阳性的SLE患者肾损发生率、活动性狼疮发生率及抗dsDNA抗体的阳性率均高于抗C1qAb阴性患者（P〈0．05）。结论血清抗C1qAb与SLE肾脏损害密切相关,其还可作为判断SLE病情活动的指标。     

Antiphospholipid Antibodies are Associated with Low Levels of Complement C3 and C4 in Patients with Systemic Lupus Erythematosus

Complement activation and low complement levels are common in systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are found in about 30‐40% of patients with SLE. This study aimed to investigate the association between aPL and complement levels in patients with SLE. Serum samples were collected from 269 patients with SLE enrolled in the Norwegian Systemic Connective Tissue and Vasculitis Registry (NOSVAR) during 2003‐2009, and from 353 controls. All samples were analysed for anti‐β2 glycoprotein 1 (anti‐β2GP1) and anticardiolipin antibodies (aCL), C‐reactive protein (CRP) and complement components C3 and C4. Median CRP level was significantly higher in cases than in controls (2.06 versus 0.90 mg/l; P < 0.0001). No significant difference in CRP was found between SLE patients with or without aPL (2.09 versus 1.89; P = 0.665). Median C3 levels were similar in cases (1.03 g/l) and controls (1.00 g/l), whereas median C4 levels were 0.16 g/l in cases versus. 0.19 in controls (P < 0.0001). However, aPL‐positive SLE patients had significantly lower median C3 levels (0.92 versus. 1.07 g/l; P = 0.001) and C4 levels (0.11 versus 0.16 g/l; P < 0.0001) compared to aPL‐negative patients. Lower C3 and C4 values in aPL‐positive SLE patients may reflect a higher consumption of C3 and C4 due to more pronounced complement activation in aPL‐positive SLE patients compared to SLE patients without aPL.     

Polynucleotide Immune Complexes in Serum and Glomeruli of Patients with Systemic Lupus Erythematosus

Several types of antipolynucleotide antibodies were eluted by acid buffer or deoxyribonuclease treatment of glomeruli obtained from nine kidneys from patients with systemic lupus erythematosus (SLE). Anti-SDNA antibodies were found concentrated over serum levels in eight eluates, anti-NDNA in six eluates and anti-RNA Pr in four eluates; anti-DSRNA antibodies were not demonstrable in any eluate tested. Deoxyribonuclease treatment eluted a high incidence and greater quantity of anti-NDNA and anti-SDNA antibody, whereas anti-RNA Pr antibody was mainly eluted by acid buffer. Simultaneous studies of antibody and antigen in serial serum specimens and in glomeruli suggested that complexes of SDNA antibody or antigen excess were frequently deposited in SLE kidneys, in addition to complexes containing anti-NDNA and anti-RNA Pr. It was observed that studies of antibody titers alone were inadequate for predicting the types of complexes deposited in the kidney. Either antigen excess could obscure detection of humoral antibody or extremely high titers of antibody as observed for RNA Pr are not conducive to the formation of kidney localizing immune complexes in the absence of antigen. Immunofluorescence studies demonstrated the presence of SDNA antigen in most cases from which anti-SDNA antibody was eluted providing direct evidence for the presence of SDNA-anti-SDNA complexes in renal glomeruli. A study of complement components indicated that Clq was absent from cases in which little or no SDNA was deposited in renal glomeruli; although all nephritic kidneys demonstrated C3 deposits. Several hypotheses accounting for this observation are discussed, including the probable utilization of the alternate pathway by certain types of complexes and a direct reaction between C1q and circulating or tissue-bound NDNA or SDNA.     

血液相关指标与系统性红斑狼疮活动性分析

目的探讨白细胞(white blood cell,WBC)、红细胞(red blood cell,RBC)、血小板(platelet,PLT)、血红蛋白(hemoglobin,HB)、淋巴细胞绝对值(absolute lymphocyte value,Lym#)、平均血小板体积(mean platelet volume,MPV)与系统性红斑狼疮(systemic lupus erythematosus,SLE)病情活动性关系。方法随机收集2017年12月至2018年11月我院风湿免疫科SLE病人样本37例,根据SLE活动指数(systemic lupus erythematosus disease activity index,SLEDAI)分为活动组与非活动组,同时收集同期健康体检者22例作为对照组,检测样本的血常规相关指标Lym#、MPV、WBC、RBC、HB、PLT及血清补体3(serum complement 3,C3),红细胞沉降率(erythrocyte sedimentation rate,ESR),比较各指标之间的相关性。结果 SLE活动组与对照组比较,Lym#、C3、MPV、PLT、RBC、HB均小于对照组,差异具有统计学意义(P<0.05),两组间WBC无差异(P>0.05)。SLE非活动组与对照组间比较,Lym#、RBC、HB差异有统计学意义(P<0.05),二组间WBC、PLT、C3、MPV无差异(P>0.05)。SLE活动组与非活动组比较,活动组MPV、Lym#、C3、WBC、PLT、HB均低于非活动组,差异有统计学意义(P<0.05),ESR高于非活动组(P<0.05),两组间RBC无统计学差异(P>0.05)。WBC、RBC、HB、PLT、Lym#、MPV与SLE活动性指标SLEDAI、ESR呈负相关,与C3呈正相关。结论 WBC、RBC、HB、 PLT、Lym#、MPV可作为系统性红斑狼疮活动性的观察指标。     

Genetic Contribution to Carotid Vascular Disease in Patients with Systemic Lupus Erythematosus

Objective We investigated whether stromelysin, a candidate gene in atherogenesis, plays a role in atherogenesis of systemic lupus erythematosus (SLE), a leading cause of mortality in SLE. Patients and Methods A genetic study using polymorphism located in the promoter region of stromelysin was performed in 55 Italian patients with SLE. Carotid intimal-medial thickness (IMT) was evaluated by B mode ultrasonography. Results All patients with an “abnormal” (≥0.9 mm) IMT carried at least one 6A allele, and the degree of IMT was significantly greater in patients carrying at least one 6A allele (0.63 ± 0.22 vs 0.43 ± 0.04 mm, 5A/6A + 6A/6A vs 5A/5A, p = 0.018). Conclusion Our data show that polymorphism of stromelysin promoter may be relevant for SLE-related cardiovascular disease.     

The Tie2 Receptor Antagonist Angiopoietin-2 in Systemic Lupus Erythematosus: Its Correlation with Various Disease Activity Parameters

Background: Systemic lupus erythematosus is one of the autoimmune diseases characterized by multisystem involvement associated with autoantibody and immune complex vasculitis along with endothelial cell damage. Objective: to study the possible role of Angiopoietin- 2 (Ang-2) as a recently highlighted inflammatory and angiogenic mediator in the pathogenesis of SLE and its correlation with the state of another inflammatory marker, P-Selectin, as well as with various markers of the disease activity. Patients and methods: The present study included 3 main groups: active SLE patients (group I), inactive SLE patients (group II) and healthy normal control subjects (group III). Groups I and II were subjected to disease activity assessment using the SLEDAI scoring system and measurement of plasma Ang-2 and P-Selectin by ELISA in addition to various laboratory investigations to assess disease activity as: Complete blood count, ESR, serum creatinine, C3, C4 and 24-h urinary proteins. Results: The mean level of Plasma Ang-2 and P-selectin showed a high significant increase in active group compared to inactive SLE patients and control subjects (p < 0.001).There was a significant positive correlation between Ang-2, P-Selectin, and each of SLEDAI score and 24-h urinary proteins in all SLE patients as well as in the active group, and Ang-2 was a significant independent marker for proteinuria. A significant negative correlation was found between Ang-2, P-Selectin and each of C3, C4. Ang-2 and P-Selectin showed a high sensitivity and specificity in the patients with SLE. Conclusion: Our study suggests that Ang-2 may be a more useful marker than P-Selectin, C3 and C4 in the assessment of disease activity.     

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.