Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood-onset inflammatory disease characterized by arthritis accompanied by systemic auto-inflammation and extra-articular symptoms. While recent advances have unraveled a range of risk factors, the pathomechanisms involved in SJIA and potential prognostic markers for treatment success remain partly unknown. In this study, we included 70 active SJIA and 55 healthy control patients from the National Center for Biotechnology Information to analyze for differentially expressed genes (DEGs) using R. Functional enrichment analysis, protein-protein interaction (PPI), and gene module construction were performed for DEGs and hub gene set. We additionally examined immune system cell composition with CIBERSORT and predicted prognostic markers and potential treatment drugs for SJIA. In total, 94 upregulated and 24 downregulated DEGs were identified. Two specific modules of interest and eight hub genes (ARG1, DEFA4, HP, MMP8, MMP9, MPO, OLFM4, PGLYRP1) were screened out. Functional enrichment analysis suggested that complex neutrophil-related functions play a decisive role in the disease pathogenesis. CIBERSORT indicated neutrophils, M0 macrophages, CD8+ T cells, and naïve B cells to be relevant drivers of disease progression. Additionally, we identified TPM2 and GZMB as potential prognostic markers for treatment response to canakinumab. Moreover, sulindac sulfide, (-)-catechin, and phenanthridinone were identified as promising treatment agents. This study provides a new insight into molecular and cellular pathogenesis of active SJIA and highlights potential targets for further research.

中文翻译：

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活动性全身性幼年特发性关节炎中改变的分子途径和预后标志物：综合生物信息学分析。

全身性幼年特发性关节炎（SJIA）是一种严重的儿童期炎症性疾病，其特征是关节炎伴有全身性自身炎症和关节外症状。虽然最近的进展揭示了一系列风险因素，但 SJIA 中涉及的病理机制和治疗成功的潜在预后标志物仍然部分未知。在这项研究中，我们包括来自国家生物技术信息中心的 70 名活跃的 SJIA 和 55 名健康对照患者，使用 R 分析差异表达基因 (DEG)。功能富集分析、蛋白质-蛋白质相互作用 (PPI) 和基因模块构建是对 DEGs 和 hub 基因集进行。我们还用 CIBERSORT 检查了免疫系统细胞组成，并预测了 SJIA 的预后标志物和潜在的治疗药物。总共，鉴定了 94 个上调和 24 个下调的 DEG。筛选出两个感兴趣的特定模块和八个中心基因（ARG1、DEFA4、HP、MMP8、MMP9、MPO、OLFM4、PGLYRP1）。功能富集分析表明，复杂的中性粒细胞相关功能在疾病发病机制中起决定性作用。CIBERSORT 指出中性粒细胞、M0 巨噬细胞、CD8+ T 细胞和幼稚 B 细胞是疾病进展的相关驱动因素。此外，我们将 TPM2 和 GZMB 确定为对 canakinumab 治疗反应的潜在预后标志物。此外，硫化舒林酸、(-)-儿茶素和菲啶酮被确定为有前景的治疗剂。这项研究为活性 SJIA 的分子和细胞发病机制提供了新的见解，并突出了进一步研究的潜在目标。