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Type 1 interferon signature and allograft inflammatory factor-1 contribute to refractoriness to TNF inhibition in ankylosing spondylitis

Author

Listed:
  • Woogil Song

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Eunyoung Emily Lee

    (Korea Institute of Radiological and Medical Sciences)

  • Seongwan Park

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Baekgyu Choi

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Min-Gang Kim

    (Seoul National University College of Medicine)

  • Seo Yoon Ban

    (Seoul National University College of Medicine)

  • Se Rim Choi

    (Hanyang University Hospital for Rheumatic Diseases)

  • Jeong Yeon Kim

    (Seoul National University College of Medicine
    Inc)

  • Seon Uk Kim

    (Seoul National University College of Medicine)

  • Jong-Il Kim

    (Seoul National University College of Medicine)

  • Eui-Cheol Shin

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Inkyung Jung

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Jeong Seok Lee

    (Korea Advanced Institute of Science and Technology (KAIST)
    Inc)

  • Eun Young Lee

    (Seoul National University College of Medicine)

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.

Suggested Citation

  • Woogil Song & Eunyoung Emily Lee & Seongwan Park & Baekgyu Choi & Min-Gang Kim & Seo Yoon Ban & Se Rim Choi & Jeong Yeon Kim & Seon Uk Kim & Jong-Il Kim & Eui-Cheol Shin & Inkyung Jung & Jeong Seok Le, 2025. "Type 1 interferon signature and allograft inflammatory factor-1 contribute to refractoriness to TNF inhibition in ankylosing spondylitis," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60445-6
    DOI: 10.1038/s41467-025-60445-6
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