Song Woogil, Lee Eunyoung Emily, Park Seongwan, Choi Baekgyu, Kim Min-Gang, Ban Seo Yoon, Choi Se Rim, Kim Jeong Yeon, Kim Seon Uk, Kim Jong-Il, Shin Eui-Cheol, Jung Inkyung, Lee Jeong Seok, Lee Eun Young
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Division of Rheumatology, Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Republic of Korea.
Nat Commun. 2025 Jul 1;16(1):5531. doi: 10.1038/s41467-025-60445-6.
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that primarily affects the enthesis and may culminate in bony ankylosis of the spine. Despite TNF inhibitor (TNFi) being foundational in managing active inflammation, 30-40% of patients with AS remain non-responsive. Through longitudinal and multi-omics profiling of peripheral blood mononuclear cells from TNFi-receiving patients with AS, here we reveal that elevated type I IFN signatures at baseline are associated with poor TNFi response, leading to a paradoxical enhancement of IFN signatures and Th17 responses following TNFi therapy. Among type I IFN-related genes, we identify and validate AIF-1 as a predictive biomarker reflecting the inherent IFN signature that differentiates responders from non-responders. AIF-1 also contributes to an inflammatory cycle by increasing IFNα receptor expression and Th17 responses. In summary, our findings advocate for a personalized approach to managing AS by considering individual variations in AIF-1 levels and IFN signatures.
强直性脊柱炎（AS）是一种慢性炎症性关节炎，主要影响附着点，并可能最终导致脊柱骨性强直。尽管肿瘤坏死因子抑制剂（TNFi）是控制活动性炎症的基础药物，但仍有30%-40%的AS患者对此无反应。通过对接受TNFi治疗的AS患者外周血单个核细胞进行纵向和多组学分析，我们发现基线时I型干扰素特征升高与TNFi反应不佳相关，导致TNFi治疗后干扰素特征和Th17反应出现反常增强。在I型干扰素相关基因中，我们鉴定并验证了AIF-1作为一种预测生物标志物，它反映了区分反应者和无反应者的固有干扰素特征。AIF-1还通过增加IFNα受体表达和Th17反应促进炎症循环。总之，我们的研究结果提倡通过考虑AIF-1水平和干扰素特征的个体差异，采用个性化方法来管理AS。
