BMC Med：系统性青少年特发型关节炎发病的关联性分析

2012年10月24日系统性的青少年特发型关节炎（Systemic juvenile idiopathic arthritis，SJIA）是青少年特发型关节炎的一个亚型，但是由于其系统性的炎症常常导致患者发热、出疹以及发生浆膜炎。近日，刊登在BMC Medicine上的一篇研究报告揭示了SJIA患者的关节炎和全身性系统组分直接相关，但是涉及SJIA相关的炎症路径，相比多关节炎的青少年特发型关节炎（POLY）并不相同。

所有被诊断为SJIA的患者的症状都会类似于其它的疾病，比如病毒感染或者川崎氏病的症状，但是持续性的SJIA就会导致慢性关节炎的发生。自身抗体的缺乏以及其它的风湿样因子可以导致患者出现不像少年关节炎一样的症状，SJIA可以被分为自发炎症而不是自发免疫。

来自斯坦福大学医学院等处的研究者研究了在SJIA或POLY儿童患者血液中表达的基因，当这些基因进行生化反应途径比如IL信号、CD40信号或者与免疫系统交流等过程中，其表达在SJIA患者的红细胞沉降率过程中发生的比较明显，而红细胞沉降率是和关节炎症相关的一个标志物。

研究者解释道，在我们的研究中，我们识别了SJIA系统性和关节炎的组分参与的分子信号路径，我们发现SJIA炎症所涉及的路径和POLY所涉及的路径并不相同，这或许可以解释其所影响的器官的不同。甚至在SJIA中，其不同的路径也会和疾病发生的不同阶段相关，深入的研究将帮助研究者开发出治疗疾病的新型疗法。

与关节炎相关的拓展阅读：

• NEJM： Tocilizumab可有效治疗全身性幼年型特发性关节炎
• NEJM：Canakinumab可有效治疗全身型幼年特发性关节炎
• Arthrit Care Res：药物来氟米特安全和有效地治疗银屑病关节炎
• The EMBO J：抗炎机制或揭示风湿性关节炎的新型疗法
• A&R: 接受甲氨蝶呤治疗的类风湿关节炎患者合用Tofacitinib（CP-690,550）的临床随机研究 更多信息请点击：有关关节炎更多资讯

Correlation analyses of clinical and molecular findings identify candidate biological pathways in systemic juvenile idiopathic arthritis

Background Clinicians have long appreciated the distinct phenotype of systemic juvenile idiopathic arthritis (SJIA) compared to polyarticular juvenile idiopathic arthritis (POLY). We hypothesized that gene expression profiles of peripheral blood mononuclear cells (PBMC) from children with each disease would reveal distinct biological pathways when analyzed for significant associations with elevations in two markers of JIA activity, erythrocyte sedimentation rate (ESR) and number of affected joints (joint count, JC). Methods PBMC RNA from SJIA and POLY patients was profiled by kinetic PCR to analyze expression of 181 genes, selected for relevance to immune response pathways. Pearson correlation and Student's t test analyses were performed to identify transcripts significantly associated with clinical parameters (ESR and JC) in SJIA or POLY samples. These transcripts were used to find related biological pathways. Results Combining Pearson and t test analyses, we found 91 ESR-related and 92 JC-related genes in SJIA. For POLY, 20 ESR-related and 0 JC-related genes were found. Using Ingenuity Systems Pathways Analysis, we identified SJIA ESR-related and JC-related pathways. The two sets of pathways are strongly correlated. In contrast, there is a weaker correlation between SJIA and POLY ESR-related pathways. Notably, distinct biological processes were found to correlate with JC in samples from the earlier systemic plus arthritic phase (SAF) of SJIA compared to samples from the later arthritis-predominant phase (AF). Within the SJIA SAF group, IL-10 expression was related to JC, whereas lack of IL-4 appeared to characterize the chronic arthritis (AF) subgroup. Conclusions The strong correlation between pathways implicated in elevations of both ESR and JC in SJIA argues that the systemic and arthritic components of the disease are related mechanistically. Inflammatory pathways in SJIA are distinct from those in POLY course JIA, consistent with differences in clinically appreciated target organs. The limited numbers of ESR-related SJIA genes that also are associated with elevations of ESR in POLY-JIA implies that the SJIA associations are specific for SJIA, at least to some degree. The distinct pathways associated with arthritis in early and late SJIA raise the possibility that different immunobiology underlies arthritis over the course of SJIA.