系统性红斑狼疮患者血清可溶性协同共刺激分子ICOSL和VTCN1水平变化及临床意义

发布时间：2018-05-29 19:36

本文选题：可诱导共刺激分子 + v-set域含有T细胞激活抑制剂1　；参考：《安徽医科大学》2017年硕士论文

【摘要】：背景系统性红斑狼疮(systemic lupus erythematosus,SLE),是细胞和体液免疫功能紊乱引起的自身免疫性疾病,狼疮性肾炎(lupus nephritis,LN)是其严重的并发症之一。ICOSL(Inducible costimulatory molecule ligand)和VTCN1(V-set domain containing T cell activation inhibitor 1,VTCN1,即B7-H4)是B7/CD28家族成员,是两个重要的协同共刺激分子,在自身免疫性疾病中起到举足轻重的作用。目的检测SLE患者血清中B7/CD28家族可溶性分子ICOSL(soluble ICOSL,s ICOSL)和VTCN1(soluble VTCN1,s VTCN1)浓度,分析其水平改变与SLE疾病活动度、临床表型、实验室检查指标之间的关系,并探索其在SLE发病机制中的作用,为SLE诊断、治疗提供指导意义。方法纳入49例2015年3月至2015年8月在安徽医科大学第一附属医院和第二附属医院明确诊断为SLE的患者,并选择年龄、性别匹配的健康对照者33例。收集患者和健康对照者人口学资料、临床表现和实验室检查指标。与此同时使用ELISA方法检测SLE患者和健康对照组血清s ICOSL、s VTCN1水平。分析s ICOSL、s VTCN1血清水平与SLE活动度、临床分型和实验室检查指标之间的相关性。结果(1)与健康对照组相比,血清中s ICOSL浓度在SLE组显著降低,并且在LN、活动组中也显著降低(SLE:1.63±0.67ng/ml,P=0.004;LN:1.66±0.67ng/ml,P=0.008;活动组:1.63±0.67ng/ml,P=0.003;对照组:2.17±0.75ng/ml),差异有统计学意义;而血清中s VTCN1浓度在SLE及LN组较健康对照组明显升高(0.63±0.26 vs 0.52±0.11ng/ml,P=0.006;0.66±0.27 vs 0.52±0.11ng/ml,P=0.008),差异有统计学意义。(2)与非活动组相比,活动组血清s ICOSL水平无明显差异,而活动组s VTCN1水平显著降低(0.54±0.19 vs 0.74±0.29 ng/ml,P=0.002),差异有统计学意义。狼疮性肾炎组与非狼疮性肾炎组s ICOSL、s VTCN1浓度均并未发现统计学差异。(3)SLE患者血清s ICOSL水平与SLEDAI无明显相关性,而血清s VTCN1水平与SLEDAI成负相关(r=-0.3055,P=0.022)。SLE患者血清s ICOSL、s VTCN1的浓度与抗双链DNA滴度、血沉ESR、补体(C3、C4)、总蛋白、血肌酐、血尿素氮均未发现相关性。(4)SLE和LN患者大多数使用了免疫抑制剂和激素,但是其并未对血清s ICOSL、s VTCN1浓度产生明显影响(P=0.495,P=0.371)。结论SLE患者血清中s ICOSL水平降低、s VTCN1水平升高、并且s VTCN1水平与疾病活动度呈负相关,均提示ICOSL、VTCN1可能参与了SLE的发生发展,但是其具体作用机制尚需进一步研究。
[Abstract]:Background systemic lupus erythematosus (lupus) is an autoimmune disease caused by cellular and humoral immune dysfunction. Lupus nephritis (LN) is one of its severe complications. ICOSL Inducible costimulatory molecule ligand) and VTCN1(V-set domain containing T cell activation inhibitor 1 / VTCN1 (B7-H4) are members of the B7/CD28 family. It is an important costimulatory molecule and plays an important role in autoimmune diseases. Objective to detect the serum concentrations of soluble ICOSL(soluble ICOSLS (ICOSL(soluble ICOSL) and VTCN1(soluble VTCN1s (VTCN1) in the serum of patients with SLE, and to analyze the relationship between the changes of their levels and the disease activity, clinical phenotype and laboratory parameters of SLE, and to explore their role in the pathogenesis of SLE. To provide guidance for the diagnosis and treatment of SLE. Methods 49 patients with SLE were selected from the first affiliated Hospital and the second affiliated Hospital of Anhui Medical University from March 2015 to August 2015, and 33 healthy controls with age and sex matching were selected. Demographic data, clinical manifestations and laboratory findings of patients and healthy controls were collected. At the same time, ELISA method was used to detect the serum levels of sICOSL VTCN1 in patients with SLE and healthy controls. To analyze the correlation between serum level of sICOSLS VTCN1 and SLE activity, clinical classification and laboratory examination. Results (1) compared with the healthy control group, the serum s ICOSL concentration in the SLE group was significantly lower than that in the control group, and in the active group it was also significantly lower than that in the active group (1.63 卤0.67 ng / ml 路ml ~ (-1) LN: 1.66 卤0.67 ng 路ml ~ (-1) P ~ (0.008); in the active group, it was 1.63 卤0.67 ng / ml ~ (-1) P ~ (0.003); in the control group, 2.17 卤0.75 ng 路ml ~ (-1) 路L ~ (-1); there was a significant difference in the control group (n = 2.17 卤0.75 ng / ml). The serum s VTCN1 concentration in the SLE and LN groups was significantly higher than that in the healthy control group (0.63 卤0.26 vs 0.52 卤0.11ng / ml 路ml ~ (-1) 0.66 卤0.27 vs 0.52 卤0.11ng / ml 路ml ~ (2) P ~ (). There was no significant difference in serum s ICOSL levels between the active group and the inactive group. The level of s VTCN1 in active group was significantly lower than that in active group (0.54 卤0.19 vs 0.74 卤0.29 ng / ml). In lupus nephritis group and non-lupus nephritis group, there was no significant correlation between the serum s ICOSL level and SLEDAI in patients with lupus nephritis and non-lupus nephritis. The serum s VTCN1 level was negatively correlated with SLEDAI. The serum sICOSLs VTCN1 level and anti-double-stranded DNA titer, erythrocyte sedimentation rate (ESR), complement C _ (3) C _ (4), total protein, serum creatinine, blood urea nitrogen were not found to be related to the level of serum sICOS VTCN1 and immunosuppressive agents and hormones were found in most of the patients with SLE and LN. However, it had no significant effect on the concentration of serum sICOSLS VTCN1. Conclusion the level of s ICOSL in serum of SLE patients decreased and the level of s VTCN1 increased, and the level of s VTCN1 was negatively correlated with the disease activity, which suggested that the level of VTCN1 VTCN1 might be involved in the occurrence and development of SLE, but the mechanism of its action should be further studied.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R593.241

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