凋亡相关分子sFas与SLE患者器官/系统损害的关联研究

目的比较系统性红斑狼疮患者(systemic lupus erythematosus,SLE)和正常对照两组间的血清可溶性Fas(sFas)的表达水平,分析sFas与SLE患者器官/系统损害之间的关系,并探讨sFas与患者器官/系统损害的关联是否涉及细胞凋亡.方法病例选自两所三甲医院住院SLE患者(n=68),以健康志愿者为对照(n=69);参照系统性红斑狼疮疾病活动性指数(SLEDAI)和系统性红斑狼疮损伤指数(SLICC/ACR DI)量表,设计问卷,收集患者的一般情况和器官/系统损害资料.利用流式细胞仪,采用连接素V(Annexin V,AV)和碘化丙啶(propidium iodide,PI)双染法检测研究对象的PB-MCs早期凋亡率;以双抗夹心酶联免疫吸附实验测定研究对象外周血sFas的表达水平.结果SLE患者组(n=68)的血清sFas表达水平(6876.27±1979.38 pg/ml)高于正常对照组(3275.08±1023.01 PS/ml)(t=13.405,P＜0.01),与SLE-DAI(r=0.274,t2.86,P=0.005)和SLICC/ACR DI(rs=0.437,t3.95,P＜0.01)均呈正相关,与PBMCs的早期凋亡率也呈正相关(r=0.395,t=3.49,P＜0.01).CNS损害SLE组(n=11)的血清sFas水平9576.60±3654.70 pg/ml高于非CNS损害SLE组(n=57)6629.37±2372.30 pg/ml(q=6.42,P＜0.05),并且两者均高于正常对照组(n=69)3275.08±1023.01 pg/ml(F=75.10,P＜0.01,q=13.93,P＜0.05;q=13.45,P＜0.05).肾脏损害SLE组(n=33)的血清sFas水平10968.45±4814.60 pg/ml高于非肾脏损害SLE组(n=35)6502.78±3971.00 pg/ml(q=8.20,P＜0.05),并且两者均高于正常对照组(n=69)3275.08±1023.01 PS/ml(F=66.33,P＜0.01,q=16.20,P＜0.05;q=6.93,P＜0.05).浆膜炎SLE组(n=6)的血清sFas水平10376.69±4149.50 pg/ml高于非浆膜炎SLE组(n=62)6718.34±2351.80 ps/ml(q=6.30,P＜0.05),并且两者均高于正常对照组(n=69)3275.08±1023.01 PS/ml(F=75.71,P＜0.01,q=12.28,P＜0.05;q=14.48,P＜0.05).结论SLE患者的外周血清可溶性sFas的表达水平增加,且血清可溶性sFas与患者的器官/系统损害关系密切.sFas表达升高、凋亡亢进在SIE发病机制中发挥重要作用,sFas可较好反映患者器官/系统损害情况.     

SLE患者临床表现、自身抗体的相关性分析及其性别、年龄特征调查刎

目的 探讨系统性红斑狼疮患者临床表现、自身抗体的相互关系及性别、年龄特征,有助于更深入研究疾病、发现潜在损害,并为发病机制研究提供线索.方法 采用回顾性研究,按不同性别、年龄(育龄期为15～49岁,育龄期后为≥50岁)分析1 012名系统性红斑狼疮患者的主要自身抗体和临床表现,并对二者间的联系进行相关性分析.结果 育龄期后组易患高血压、肺部感染,而蝶形/盘状红斑、狼疮肾炎、发热、脱发等症状发生较育龄期组为少,育龄期后组抗dsD-NA抗体、抗SSA抗体、抗SSB抗体、抗uRNA抗体、抗Sm抗体阳性率均较育龄期组低;抗dsDNA抗体与狼疮肾炎、关节炎、发热有显著关联,抗Sm抗体与关节炎、中枢神经损害有显著关联,抗uRNP抗体与雷诺现象、关节炎有显著关联,抗磷脂抗体与血管栓塞、高血压、发热有显著关联,抗核抗体与血管栓塞有关联,抗SSA/SSB抗体不与临床表现存在关联.结论 男女SLE患者临床表现无明显差异,抗SSA、SSB抗体阳性率男性明显低于女性,育龄期后组较育龄期组疾病活动性低,自身抗体与临床表现间存在一定关联,如抗dsDNA抗体与肾炎/关节炎、抗磷脂抗体与血管栓塞/发热等.     

伴有白细胞减少长期发热的病因诊断

长期发热可由多种疾病引起,国内文献已有报道。但伴有白细胞减少的长期发热的病因分析,尚未见描述。本文拟就1971～1986年15年来本院收治的病程超过4周的54例白细胞低于4×10~3/L的长期发热的病因进行分析,并对诊断中的若干问题加以讨论。     

调节性T细胞亚群变化与五种自身免疫性疾病的关系

机体通过调控活化自身反应性T细胞，可保护机体免受持续有害免疫反应的损害。最近研究表明，调节性T细胞（简称Treg）可主动抑制逃逸出被动耐受机制的自身反应性T细胞。目前已发现的Treg亚群有多种，CD4^＋CD25＋T细胞是研究较为深入的一类，大量动物实验证明，其数量缺乏和功能紊乱将导致严重或致命的自身免疫性疾病。但对其在人自身免疫性疾病发生中的作用目前还不明确，故本研究分析与探讨其与5种自身免疫性疾病的发病关系。     

联合检测C1q抗体、双链DNA抗体对系统性红斑狼疮的诊断价值

目的探讨联合检测C1q抗体、双链DNA（dsDNA）抗体对狼疮活动和狼疮性肾炎的价值。方法58例系统性红斑狼疮分为疾病活动和疾病稳定组、狼疮性肾炎和非狼疮性肾炎组，酶联免疫吸附法检测血清C1q抗体和dsDNA抗体水平，比较两抗体单个和联合检测对疾病活动和狼疮性肾炎的价值。结果C1q抗体和dsDNA抗体阳性对疾病活动的敏感性分别为63．88％和69．44％，特异性分别为81．82％和86．36％；两抗体联合对疾病活动的敏感性为83．33％，特异性为72．73％，两抗体的一致率为70．68％。疾病活动组两抗体阳性率和抗体水平显著高于疾病稳定组；两抗体与系统性红斑狼疮疾病活动指数、血沉、IgG、球蛋白水平显著正相关，与C3、C4及白蛋白水平显著负相关。狼疮性肾炎组dsDNA水平显著高于非狼疮性肾炎组，尿蛋白≥（＋＋）患者C1q抗体水平显著增高。结论C1q抗体和dsDNA抗体都是狼疮疾病活动的指标，两抗体都与狼疮性肾炎有关，联合检测可以提高疾病活动检出率。     

肽酰基精氨酸脱亚氨酶-4基因多态性与类风湿关节炎的相关性

目的 肽酰基精氨酸脱亚氨酶基因4-94位点(PADI4-94)和4-104位点(PADI4-104)基因的单核苷酸多态性(SNPs)与类风湿关节炎(RA)易感性的关系.方法 采用聚合酶链反应-连接酶检测反应(PCR-LDR)方法 鉴定116例RA患者和100名健康体检者基因及基因型,计算其频率,用X2检验统计分析.用酶联免疫吸附试验(ELISA)法检测RA外周血抗PADl4抗体及PADI4蛋白水平.结果①PADI4-94及PADI4-104位点存在A和G 2种等位基因,A/A,G/G和A/G 3种基因型,RA组/健康组PADI4-94等位基因A、G及其A/A、G/G和A/G基因型频率分别是0.460/0.392、0.540/0.608,0.204/0.186、0.283/0.402和0.513/0.412,2组差异无统计学意义(X2=1.996,P=0.157;X2=3.407,P=0.182);RA组/健康组PADI4-104等位基因A、G及其A/A、G/G和A/G基因型频率分别是0.412/0.345、0.588/0.655,0.150/0.144、0.32710.454和0.522/0.402,2组差异无统计学意义(X2=1.937,P=0.164;X2=3.780,P=0.151).③RA组PADI4-94/PADI4-104各基因型间红细胞沉降率(ESR),RA疾病活动关节评分28(DAS28)评分,C反应蛋白(CRP),抗环瓜氨酸肽(CCP)抗体,PADI4蛋白量及抗PADI4抗体水平差异无统计学意义(P值分别为0.46/0.67,0.62/0.57,0.12/0.23,0.81/0.43,0.78/0.75,0.38/0.31).结论 我国人群PADI4-94和PADI4-104两位点存在多态性,但其与RA的易感性无关.     

系统性红斑狼疮患者外周血CD4+CXCR5+滤泡辅助性T细胞样细胞的变化及糖皮质激素对其的影响

Objective To investigate the frequencies of CD4+CXCR5+T cells in the CD4+T cells of peripheral blood of patients with systemic lupus erythematosus (SLE) and the effect of glucocorticoid on it.Methods Frequencies of CD4+CXCR5+T cell were analyzed by flow cytometry in 45 active,20 inactive SLE patients and 20 healthy controls.Differences between groups and the effect of glucocorticoid were analyzed.Meanwhile, the expression of CXCR5 on CDI9+B cells was analyzed. Independent sample t test was used for statistical analysis between twogroups, ANOVA was applied for data analysis between 3 groups,,nonparameterical Spearman's analysis was used for correlation analysis and repeated measurement ANOVA were used to compare the parameters before and after treatment. Results The percentage of CD4+CXCR5+ in CD4+T cells was increased in patients with SLE compared with healthy controls[(16±7)% vs (12±3)%, P＜0.01].It was increased in patients with active SLE [(18±7)%] compared with healthy controls (P＜0.05) but there was no significant difference between inactive SLE[(11±4)%] and healthy controls(P＞0.05). The percentage in patients with LN was higher than that in patients without LN, but without significant difference[(18±7)%vs (14±7)%, P=0.05 ]. The percentage of CD4+CXCR5+T cells was positively correlated with SLEDAI,the titer of ANA and level of ESR but negatively correlated with the level of C3 (P<0.05 for each).No correlation was found between duration and the levels of CRP and immunoglobulin.. The percentage in patients with high anti-dsDNA group was also higher than that of the low group, but no differences were found between anti-Sm antibody positive and negative groups neither between anti-SSA/SSB antibody positive and negative groups(P＞0.05 for each).The expression level of CXCR5 on CD19+B cells in active SLE patients was lower than that of healthy controls[(85±11)% vs (94±3)%, P＜0.05 ]. The percentages of CD4+CXCR5+T cells in 10 untreated active SLE patients were decreased at day 1,day 3 and day 7 after being treated with dexamethasone (20mg/d) when compared with those before the treatment (P＜0.05 for each), but the percentages of CD19+CXCR5+B cells had no significant change (P＞0.05 for each).Conclusion These results demonstrate that the abnormality of CD4+CXCR5+T cells may play an important role in the pathogenesis of SLE.     

系统性红斑狼疮的生物治疗进展

系统性红斑狼疮(systemic lupus elythematosus,SLE)是一种病因尚不明确,以B细胞活化增殖、T细胞功能缺陷、血清中出现多种自身抗体及多器官系统受累为特征的慢性自身免疫性疾病.     

晚发系统性红斑狼疮35例临床及免疫学特点分析

目的探讨晚发系统性红斑狼疮患者的临床表现和相关实验室检查特点。方法回顾性分析35例晚发系统性红斑狼疮患者的临床表现、实验室指标和治疗情况,并和同期收治的35例初发系统性红斑狼疮患者进行比较。结果晚发系统性红斑狼疮占同期系统性红斑狼疮患者的4.3%。晚发组面部皮疹、口腔溃疡、雷诺现象的发生率较初发组少见(P<0.05),肾功能异常和继发干燥综合征的比例高于初发组(P<0.05)。晚发组抗dsDNA抗体、抗Sm抗体、抗SSA抗体、抗SSB抗体和抗RNP抗体的阳性率低于初发组(P<0.05)。晚发组确诊时的疾病活动指数(SLEDAI)低于初发组(P<0.05)。此外,晚发组联合使用免疫抑制剂的比例低于初发组(P<0.05)。结论晚发系统性红斑狼疮患者较少出现狼疮的典型临床表现和特异性自身抗体,疾病活动程度较低,治疗上较少需要联用免疫抑制剂。