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  • Title: [Expression and Clinical Significance of Semaphorin 3A in serum and mononuclear cells in patients with systemic lupus erythematosus].
    Author: Gao H, Ma XX, Guo Q, Zou YD, Zhong YC, Xie LF, Shao M, Zhang XW.
    Journal: Zhonghua Yi Xue Za Zhi; 2017 Feb 07; 97(5):370-374. PubMed ID: 28219195.
    Abstract:
    Objective: To determine the expression of Sema3A in serum and peripheral blood mononuclear cells (PBMC) of patients with systemic lupus erythematosus (SLE), to analysis the correlation of Sema3A expression and SLE clinical manifestations and laboratory indexes, and to evaluate the diagnostic value of Sema3A in patients with SLE. Methods: The concentration of serum Sema3A was detected by enzyme-linked immuno sorbent assay (ELISA) in patients with SLE, healthy controls (HC) and diseases controls. In addition, the mRNA expression level of Sema3A was examined in PBMC by real-time polymerase chain reaction. The correlation of serum Sema3A level and clinical and laboratory features of SLE patients were analyzed. Unpaired t test, Kruskal-Wallis test, Mann-Whitney U test, χ(2) test, Pearson and Spearman correlation analysis were used to statistical analysis by using SPSS 13.0. Results: (1) Serum Sema3A concentration in patients with SLE was significantly lower than that in HC groups (P<0.01). (2) Consistent with the serum level, the Sema3A mRNA level in SLE was lower than that in HC (P=0.001). And the mRNA expression of Nrp-1 in SLE was also lower than that in HC (P<0.01). (3) The serum Sema3A level in patients with SLE was positively correlated with haemoglobin (HGB) (r=0.271, P<0.013), platelet (PLT) (r=0.600, P<0.011), complement 3 (C3) (r=0.234, P=0.0027) and complement 4 (C4) (r=0.159, P=0.434) levels. Whereas, the expression of Sema3A was negatively correlated with SLE disease activity index (SLEDAI) (r=-0.286, P=0.036). (4) Area under curve illustrated by ROC curve was 0.876 (95% CI: 0.846-0.906). The best cut-off value for the diagnosis of SLE was 6.31 μg/L, with the sensitivity of 80.6% and the specificity of 77.5%. The Youden index was 0.581. Above results indicated good validity of Sema3A as a diagnostic marker for SLE. (5) The HGB, PLT, C3 and C4 levels in the group of Sema3A- positiveSLE patients (≤6.31 μg/L) were lower than that in negative group (>6.31 μg/L), while CRP level and SLEDAI of positive group was higher than that in negative group(P<0.05). In addition, the positive rate of antinuclear antibodies (P=0.046) and anticardiolipin antibody (P=0.018) in the Sema3A-negative group were also significantly higher than that of negative group. Conclusions: Sema3A and Nrp-1 was both decreased in serum and PBMC of SLE patients, suggesting that the circulating expression of Sema3A and Nrp-1 was seriously defected in SLE. Circulating Sema3A was significantly correlated with disease activity and blood damage in patients with SLE. The result of ROC curve showed that Sema3A had the potential to be a new diagnostic biomarker in SLE. 目的： 通过测定Sema3A在系统性红斑狼疮 (SLE)患者血清及外周血单个核细胞(PBMC)中的表达，分析Sema3A与SLE临床表现及相关实验室指标的相关性，并对Sema3A在SLE患者中的诊断价值进行评估。 方法： 收集SLE患者的血清，比较SLE患者Sema3A水平与其他不同结缔组织病和健康对照者的水平差异，并检测Sema3A及其受体Nrp－1的mRNA表达量。对Sema3A和SLE的临床及实验室指标进行相关性分析，评估Sema3A在SLE中的诊断价值。 结果： (1)共纳入SLE患者170例、其他结缔组织病患者[类风湿关节炎(RA)、干燥综合征(SS)、皮肌炎(DM)及系统性硬化病(SSc)]220例和健康对照组150名。SLE患者血清Sema3A的水平较健康对照组显著下降(P<0.01)，Sema3A的mRNA表达(0.63±0.76)低于健康对照组(1.01±0.85，P<0.01)，Nrp－1的表达(0.84±0.76)亦显著低于健康对照组(6.17±8.16，P<0.01)。(2)与SLE患者血清Sema3A水平正相关的临床实验室指标有：血红蛋白(r＝0.271，P<0.01)，血小板(r＝0.600，P<0.01)，补体3(C3)(r＝0.234，P<0.01)和补体4(C4)(r＝0.159，P<0.05)；与其负相关的为SLEDAI评分(r＝－0.286，P<0.05)。(3)受试者工作特征曲线(ROC)分析得出曲线下面积(AUC)为0.876，95%可信区间(CI)为0.846～0.906，cut－off值为6.31 μg/L，敏感性为0.806，特异性为0.775，Youden指数为0.581。(4)以Sema3A最佳临界值分界线，阳性组(≤6.31 μg/L)发热发生率高，血红蛋白、血小板、C3和C4水平显著低于阴性组(>6.31 μg/L)，而阳性组的C－反应蛋白(CRP)水平、SLE疾病活动指数(SLEDAI评分)、抗核抗体(ANA)及抗心磷脂抗体(ACL)的阳性率均高于阴性组(P>0.05)。 结论： SLE患者外周血Sema3A/Nrp－1表达明显缺陷，并与SLE病情活动和血液系统的损伤具有极强的相关性。ROC曲线分析显示Sema3A对SLE的识别能力均较强，具有成为SLE诊断标志物的潜力。.
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