Transcription profiling of monocytes from patients with active and inactive systemic juvenile idiopathic arthritis.. Transcription profiling of monocytes from patients with active and inactive systemic juvenile idiopathic arthritis.

Systemic juvenile idiopathic arthritis (SJIA) confers high risk for macrophage activation syndrome (MAS), a life-threatening episode of hyperinflammation driven by IFN-γ. Monocytes in SJIA display IFNγ-hyperresponsiveness, but the molecular basis of this remains unclear. The objective of this study is to identify circulating monocyte polarization phenotypes including features of interferon response. Bulk RNA-seq of purified monocytes was performed on healthy controls as well as patients with inactive SJIA (satisfy Wallace criteria for clinically inactive disease), active SJIA, new-onset SJIA (NOS), and macrophage activation syndrome (2016 MAS Classification Criteria). We observed marked transcriptional changes in patients with elevated ferritin levels. We also identified substantial overlap with multiple polarization states but little evidence of IFN-induced signature. Overall design: Monocyes from control (n=11), active (n=16), and inactive (n=10) SJIA.

全身型幼年特发性关节炎（Systemic juvenile idiopathic arthritis, SJIA）患者罹患巨噬细胞活化综合征（macrophage activation syndrome, MAS）的风险极高，该病是一种由干扰素γ（Interferon-γ, IFN-γ）驱动的致死性过度炎症综合征。SJIA患者的单核细胞呈现IFN-γ高应答特性，但其背后的分子机制尚未明确。本研究旨在鉴定循环单核细胞的极化表型，包括干扰素应答相关特征。研究团队对健康对照者、符合Wallace临床静止期疾病标准的临床静止期SJIA患者、活动期SJIA患者、新发SJIA（new-onset SJIA, NOS）患者以及符合2016年巨噬细胞活化综合征分类标准的MAS患者的纯化单核细胞开展了批量RNA测序（bulk RNA-seq）。研究观察到，铁蛋白水平升高的患者存在显著的转录组变化；同时还发现，该转录特征与多种极化状态存在大量重叠，但几乎未检测到IFN诱导的特征信号。总体实验设计：采集健康对照（n=11）、活动期SJIA患者（n=16）及临床静止期SJIA患者（n=10）的单核细胞样本。