- [Nature communications] Type 1 interferon signature and allograft inflammatory factor-1 contribute to refractoriness to TNF inhi
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- 2025-07-09 14:25:00|
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- 2025-07-09 14:25:00|
[Title]
Type 1 interferon signature and allograft inflammatory factor-1 contribute to refractoriness to TNF inhibition in ankylosing spondylitis
[Corresponding Author]
Jeong Seok Lee (chemami@kaist.ac.kr)
Inkyung Jung (ijung@kaist.ac.kr)
Eun Young Lee (elee@snu.ac.kr)
[Journal]
Nature Communications volume 16, Article number: 5531 (2025)
[Abstract]
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.
Type 1 interferon signature and allograft inflammatory factor-1 contribute to refractoriness to TNF inhibition in ankylosing spondylitis
[Corresponding Author]
Jeong Seok Lee (chemami@kaist.ac.kr)
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
- Inocras, Inc, San Diego, CA 92121, USA.
Inkyung Jung (ijung@kaist.ac.kr)
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
Eun Young Lee (elee@snu.ac.kr)
- Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
[Journal]
Nature Communications volume 16, Article number: 5531 (2025)
[Abstract]
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.