#3-66E. Unmasking the Risk: IFN-I Signatures in Still's Disease Complications (Arthritis Rheumatol, 2026)

Emergent life-threatening complications in Still’s disease, particularly interstitial lung disease (LD) and severe drug-associated immune reactions (DAIR) to IL-1 and IL-6 inhibitors, pose a significant clinical challenge. This study investigates the pathophysiological role of type I interferon (IFN-I) in these phenotypes. By analyzing whole blood RNA in a cohort of pediatric and adult patients, the authors identified a distinct subgroup with elevated IFN-I signatures linked to rare genetic variants in autophagy and TLR signaling pathways rather than disease activity. The most critical clinical insight is that combining the known risk allele HLA-DRB1*15 with a high IFN score provided superior predictive value, identifying LD and DAIR with near-perfect specificity in this cohort. However, physicians should critically note the retrospective nature of this study and the use of a cohort enriched for treatment-refractory cases, which necessitates prospective validation before widespread adoption. Nonetheless, this paper is vital for clinicians as it suggests a potential future biomarker strategy to stratify patient risk before initiating biologic therapy and points toward JAK inhibition as a therapeutic consideration for this high-risk subset.

Citation: Marques MC, et al. Type I interferon signature associates with lung disease, drug-associated immune reactions, and genetic variation in interferon-linked pathways in Still’s disease. Arthritis & Rheumatology. 2026.

DOI: 10.1002/art.70079

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