血清白细胞介素-34在银屑病关节炎骨破坏中的作用研究

Clinical research of interleukin-34 in psoriatic arthritis patients

目的 探讨血清IL-34水平与PsA骨破坏的相关性.方法 以40例PsA患者为实验组,以20例银屑病患者（银屑病组）及20名健康志愿者为健康对照组,检测3组研究对象外周血IL-34及破骨细胞相关细胞因子,包括TNF-α、细胞NF-κB受体活化因子配体（RANKL）和骨保护素（OPG）的水平,分析IL-34与外周血破骨前体细胞（OCP）的数量、疾病活动度及影像学评分间的相关性.所有数据均采用GraphPad Prism 6软件进行分析.采用多因素方差分析进行多组比较,两两比较采用q检验,采用Spearman相关分析评估各指标间的相关性.结果 PsA组患者血清IL-34的水平[（328±476） pg/ml]高于银屑病组[（33±52）pg/ml,q=3.92,P＜0.01]及健康对照组[（32±32） pg/ml,q=3.93,P＜0.01],侵蚀性PsA组高于非侵蚀性PsA组[（449±527） pghrd与（47±24） pg/ml,q=4.04,P＜0.01].PsA组患者外周血TNF-α、RANKL水平及OCP计数[（125±79） pg/ml、（488±475） pg/ml及17.7±4.8（5个视野）]均高于银屑病组[（40±22） pg/rnl、（26±3） pg/ml及5.2±0.8（5个视野）,q=7.32、6.14及2.94,P均＜0.01]及健康对照组[（41±19） pg/ml、（65±8） pg/ml及6.2±1.8（5个视野）,q=6.67、5.62及2.71,P均＜0.01],PsA组的OPG/RANKL比值（0.5±0.4）显著低于银屑病组（4.3±2.7,q=-3.30,P＜0.01]及健康对照组（1.8±0.6,q=-1.72,P＜0.01）,IL-34、TNF-α及RANKL的水平均与OCP呈正相关（r=0.10,P＜0.05;r=0.12,P＜0.05;r=0.13,P＜0.05）.结论 PsA患者尤其是侵蚀性PsA患者外周血中存在较高水平的IL-34,与OCP数量呈正相关,IL-34参与了OCP及破骨细胞的分化,进而促进骨破坏过程.因此,IL-34有望成为治疗PsA的新靶点.

Objective To investigate the relationship between interleukin （IL）-34 and bone erosions in psoriatic arthritis （PsA） patients.Methods Forty PsA patients,20 psoriasis （Ps） patients and 20 healthy volunteers were recruited into this study.The levels of IL-34 and osteoclast related cytokines [including tumor necrosis factor （TNF）-α,receptor activator of nuclear factor-κB ligand （RANKL）,osteoclast precursors （OPG）] were detected in the serum samples of all subjects.The correlations among IL-34,the number of osteoclast precursors （OCP）,disease activity and imaging scores were analyzed.All data were analyzed by graphpad prism 6.Differences between groups was analyzed with One-way analysis of variance,q tests,and Spearman＆#39;s correlation was used to explore the relation between disease activity/radiographic scores and laboratory results and followed by linear regressions.Results The serum level of IL-34 in patients with PsA [（328±476） pg/ml] was higher than that in Ps [（33±52） pg/ml,q =3.92,P〈0.01] and healthy controls [（32±32） pg/ml,q =3.93,P〈0.01],the erosive PsA group were higher than the non-erosive PsA group [（449±527） pg/ml and （47±24） pg/ml,q=4.04,P〈0.01].The levels of TNF-α,RANKL and OCP in patients with PsA [（125±79） pg/ml,（488± 475） pg/ml and （17.7±4.8） 5 sigh views] were higher than those in PS [（40±22） pg/ml,（26±3） pg/ml and （5.2± 0.8）,q=7.32,6.14 and 2.94,P〈0.01] and healthy controls [（41±19） pg/ml,（65±8） pg/ml and （6.2±1.8）,q=6.67,5.62 and 2.71,P〈0.01],whereas the OPG/RANKL ratio in PsA patients （0.5±0.4） was significantly lower than Ps patients （4.3±2.7,q=-3.30,P〈0.01） and healthy controls （1.8±0.6,q=-1.72,P〈0.01）.IL-34,TNF-α and RANKL levels were all positively correlated with OCP （r=0.10,P〈0.05;r=0.12,P〈0.05;r=0.13,P〈0.（5,respectively）.Conclusion The level of IL-34 is not only high in patients with PsA but also positively correlates with the number of OCP.In PsA,IL-34 is probably related to the OCP and osteoclast differentiation,and further participates in the process of bone destruction.Therefore,IL-34 is promising to become a new target or alternative choice for the treatment of PsA.