干燥综合征患者外周血程序性死亡分子-1／程序性死亡配体-1共刺激分子的表达及临床意义

The expression and clinical significance of programmed death-1/programmed death ligands-1 in perip- heral blood in patients with primary Sjogren＇s syndrome

目的探讨原发性干燥综合征（pSS）患者外周血单个核细胞（PBMCs）上程序性死亡分子（PD）-1和程序性死亡配体（PDL）-1的表达及生物学意义。方法应用流式细胞仪（FCM）检测62例Dss患者及15名健康对照者的PBMCs上CD4＋PD．1＋、CD8＋PD．1＋、CDl4＋PDL．1＋及CDl9＋PDL-1＋的表达率，详细记录各患者的临床资料及实验室结果，并分析PD-1／PD—L1协同抑制分子与pss患者的临床特点及疾病活动的相关性。统计学处理采用t检验，组间相关性分析采用直线相关分析。结果laSS患者外周血CD4＋PD-1＋表达（29±8）％显著高于健康对照组（23±4）％，活动期（34±8）％显著高于缓解期（27±6）％（P均〈O．01），但治疗前后差异无统计学意义；CD8＋PD．1＋表达（21±7）％显著高于健康对照组（17±6）％（P均〈0．05），活动期与缓解期、治疗前后差异均无统计学意义；pSS患者CDl4＋PDL-1＋表达（17±10）％显著低于健康对照组（24±12）％（P均〈0．05），活动期与缓解期、治疗前后差异无统计学意义；pSS患者CDl9＋PDL-1＋与健康对照组、活动期与缓解期、治疗前后差异均无统计学意义。CD4＊PD-1＋与CDl4＋PDL-1＋之间呈负相关。pSS患者CD4＋PD-1＋表达率与抗双链（ds）DNA、类风湿因子（RF）及红细胞沉降率（ESR）呈正相关，CD8＋PD-1＋表达率与免疫球蛋白（Ig）G、血小板呈正相关，CDl4＋PDL-1＋与抗dsDNA抗体、RF及补体（C）4呈负相关，CD19＋PDL-1＋与C4呈负相关。pSS患者肾脏损伤组外周血CD8＋PD-1＋的表达率显著高于无损伤组，有关节炎表现组外周血CDl4＋PDL-1＋的表达率显著低于无表现组。结论Dss患者外周血PD-1／PDL-1共刺激分子存在异常，与病情活动相关，可能参与到psS疾病中肾脏损伤及关节损伤，在pss的发病机制中起到重要作用，为pSS的治疗提供新的治疗靶点。

Objective To investigate the expression and clinical significance of programmed death （PD）-I/ programmed death ligands （PDL）-I in patients with primary Sjsgren＇s syndrome （pSS）. Methods The method of flow cytometry was used to measure the expression of CD4＋PD-1＋, CD8＋PD-1＋, CD14＋PDL-1＋ and CD19＊PDL-1＋ in 62 patients with pSS and the test results were compared with those of 15 normal controls. The linear correlation analysis was adopted to evaluate the relationship between the expression of CD4＋PD-1＋, CD8＋PD-1 ＋, CD14＋PDL-1 ＋, CD19＋PDL-1 ＋ and clinical manifestations. Comparisons between groups were performed by t test. Results The expression of CD4＋PD-1＋ was significantly higher in pSS patients （29±8）% than in normal controls （23±4）% （P〈0.01）, and significantly higher in active pSS patients （34±8）% than inactive patients （27±6）% （P〈0.01）, and there was no significant difference between untreated pSS patients （31±7）% and treated patients （31±8）%. The expression of CD8＋PD-1＋ was significantly higher in pSS patients （21±7）% than in normal controls （17±6）% （P〈0.05）, and there was no significant difference between active pSS patients （20±9）% and inactive patients （22±6）%, as well as between untreated pSS patients （26±9）% and treated patients （19±4）%. The expression of CD14＋PDL-1＊ was significantly lower in pSS patients （17±10）% than in normal controls （24±12）% （P〈0.05）, and there was no significant difference between active pSS patients （16±9）% and inactive patients （17±10）%, as well as between untreated pSS patients（17±9）% and treated patients （16±15）%. There was no significant difference between pSS patients （16±6）% and normal controls （16±7）%, so was the difference between active pSS patients （16±3）% and inactive patients （16±7）%, and between untreated pSS patients （16±6）% and treated patients （18±8）% in the expression of CD19＋PDL-1＋. The expression of CD4＋PD-1＋ was negatively correlated with the expression of CD14＋PDL-1＋. The expression of CD4＋PD-1＋ was positively correlated with the serum level of rheumatoid factor （RF）, erythrocyte sedimentation rate （ESR） and anti-ds-DNA. The expression of CD8＋PD-1＋ was positively correlated with the serum level of IgG and platelets. The expression of CD14＋PDL-1＋ was negatively correlated with the serum levels of RF, anti-ds-DNA and C4. The expression of CD19＋PDL-1＋ was negatively correlated with the serum level of C4. The expression of CD8＋PD-1＋ in the group with renal damage was significantly higher than those without renal damage group. The expression of CD14＋PDL-1~ in the group of arthralgia of pSS patients was significantly lower than patients without arthralgia. Conclusion There is PD-1/PDL-1 imbalance in pSS patients, and this is correlated with pSS activity indexes, renal injury and arthralgia, which may participate in the pathogenesis of pSS. It may be regarded as an index for pSS activity. It may provide new therapeutic targets for treatment of pSS.