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

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 contr

SUBMITTER: Song W 

PROVIDER: S-EPMC12214652 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature