复发性阿弗他溃疡患者可溶性程序性死亡受体1及可溶性程序性死亡配体1表达与免疫功能的相关性

Soluble programmed death-1 and soluble programmed death ligand 1 protein expression and immune status in patients with recurrent aphthous ulcer

目的了解复发性阿弗他溃疡(RAU)患者血清中可溶性程序性死亡受体-1(s PD-1)、可溶性程序性死亡配体-1(s PD-L1)蛋白表达与患者免疫功能状态的相关性,探讨s PD-1/s PD-L1在RAU免疫发病机制中的作用及意义。方法研究对象为30例RAU患者(轻型18例,重型5例,疱疹型7例)及18例健康人(对照组)。采用流式细胞术检测RAU患者外周血细胞免疫指标(CD3+、CD4+、CD8+、CD19+、CD16++56+),散射比浊法检测RAU患者体液免疫指标(Ig G、Ig A、Ig M、C3、C4),酶联免疫吸附测定RAU患者及健康人血清中s PD-1、s PD-L1蛋白表达,并对s PD-1、s PD-L1表达水平与RAU患者免疫功能状况及临床特征的相关性进行分析。结果与正常值相比,RAU患者CD4+水平降低,Ig M水平增高,差异有统计学意义(P<0.05)。RAU患者的s PD-1及s PD-L1蛋白表达水平高于对照组(P<0.05);进一步分析表明,轻型、重型RAU患者的s PD-1及s PD-L1蛋白表达水平高于对照组(P<0.05),而疱疹型RAU患者与对照组无统计学差异(P>0.05)。RAU患者s PD-1表达量与CD19+、C4存在正相关关系(r1=0.389,P1=0.034;r2=0.382,P2=0.037)。结论 RAU患者以细胞免疫功能低下为主,同时伴有体液免疫功能的紊乱;RAU患者s PD-1、s PD-L1蛋白高表达在一定程度上通过影响PD-1/PD-L1信号通路参与RAU免疫机制的调节,可能在RAU的免疫发病机制中起着一定作用。

Objective This study aims to investigate the possible role and significance of soluble programmed death-1 （sPD-1） /soluble programmed death ligand 1 （sPD-L1） in the immune pathogeneses of recurrent aphthous ulcer （RAU）. Methods A total of 30 RAU cases （18 cases of minor RAU, 5 cases of major RAU, and 7 cases of herpetiform ulcers） were enrolled in this study. A total of 18 healthy people served as controls. Lymphocyte subsets （CD3^＋, CD4^＋, CD8^＋, CD19^＋, and CD16^＋＋56^＋） were investigated by flow cytometric analysis. Humoral immunity （IgG, IgA, IgM, C3, and C4） was explored by nephelometry immunoassay. The sPD-1 and sPD-L1 protein levels in the sera of RAU patients were investigated by enzyme-linked immu-nosorbent assay. The correlations of the sPD-1 and sPD-L1 protein levels with the immune status and clinical characteristics of the RAU patients were analyzed by SPSS 19.0. Results The number of CD4^＋ T cells decreased and the levels of IgM antibodies increased in the RAU patients relative to those in the normal controls （P〈0.05）. The sPD-1 and sPD-L1 protein levels in the RAU patients were significantly higher than those in the control group （P〈0.05）. Meanwhile, the sPD-1 and sPD-L1 protein levels in the patients with minor and major RAU were significantly higher than those in the control group （P〈0.05）. By contrast, no significant difference was found in the patients with herpetiform RAU （P〉0.05）. Positive correlations were noted between the sPD-1 protein level and the CD19^＋ cell frequency or C4 level （r1=0.389, P1=0.034; r2=0.382, P2=0.037）. Conclusion Cellular immune hypofunction and humoral immunity disorders were found in the RAU patients. The PD-1/PD-L1 signaling pathway, which might be influenced by the involvement of sPD-1 and sPD-L1 proteins to a certain extent, may play some roles in the immune pathogenesis of RAU.