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6．31μg／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（≤6．31μg／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（＞6．31μg／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Sema3 A／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。%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 Sema 3A 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, χ2 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 Sema 3A 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 Sema 3A 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 Sema 3A had the potential to be a new diagnostic biomarker in SLE .
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