Correlation analyses of clinical and molecular findings identify candidate biological pathways in systemic juvenile idiopathic arthritis
Correlation analyses of clinical and molecular findings identify candidate biological pathways in systemic juvenile idiopathic arthritis
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DOI：
10.1186/1741-7015-10-125
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发表时间：
2012-10-23
期刊：
影响因子：
9.3
通讯作者：
Mellins, Elizabeth D.
中科院分区：
文献类型：
--
作者：
Ling, Xuefeng B.;Macaubas, Claudia;Mellins, Elizabeth D.
背景资料：临床医生长期以来一直重视系统性幼年特发性关节炎（SJIA）与多关节幼年特发性关节炎（POLY）的不同表型。我们假设，当分析与JIA活性的两个标志物（红细胞沉降率（ESR）和受累关节数量）升高的显著相关性时，每种疾病儿童的外周血单核细胞（PBMC）的基因表达谱将揭示不同的生物学途径方法：通过动力学PCR分析来自SJIA和POLY患者的PBMC RNA以分析181个基因的表达，所述181个基因被选择用于与免疫应答途径相关。进行Pearson相关性和Student t检验分析以鉴定与SJIA或POLY样品中的临床参数（ESR和JC）显著相关的转录本。结果：结合Pearson和t检验分析，我们在SJIA中发现了91个与ESR相关的基因和92个与JC相关的基因。在POLY中，共发现20个与ESR相关的基因，0个与JC相关的基因。这两组途径密切相关。相反，SJIA和POLY ESR相关通路之间的相关性较弱。值得注意的是，不同的生物过程被发现与JC从早期全身关节炎相（SAF）的SJIA的样品相比，从关节炎为主的后期（AF）的样品。在SJIA SAF组内，IL-10的表达与JC相关，而缺乏IL-4似乎是慢性关节炎（AF）subgroup.Conclusions的特征：在SJIA中ESR和JC升高的途径之间存在强相关性，这表明疾病的全身性和关节炎成分在机制上是相关的。SJIA中的炎症途径与POLY病程JIA中的炎症途径不同，这与临床评价的靶器官差异一致。与POLY患者ESR升高相关的ESR相关SJIA基因数量有限，这意味着SJIA相关性至少在某种程度上是SJIA特异性的。在早期和晚期SJIA中与关节炎相关的不同途径提高了在SJIA过程中关节炎的免疫生物学基础不同的可能性。
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 number of ESR-related SJIA genes that also are associated with elevations of ESR in POLY 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.