ArticleFrontiers in immunology2026
Autoantibodies against interleukin-1 receptor antagonist in Still's disease in adult patients, data from a multicenter cohort study.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objectives: Emerging evidence supports the presence of autoantibodies targeting interleukin-1 receptor antagonist (IL-1Ra), a regulator of IL-1 signaling, in adult-onset Still's disease (AOSD). However, existing data are limited by small cohorts and potential confounding due to prior exposure to IL-1 inhibitors. This study aimed to develop a simple and reproducible indirect ELISA for detecting anti-IL-1Ra antibodies and to assess their frequency and immunological features in IL-1 inhibitor-naïve AOSD patients. Methods: Serum samples from IL-1 inhibitor-naïve AOSD patients (n=46) and healthy controls (n=26) were analyzed using an indirect ELISA based on recombinant IL-1Ra (anakinra) as antigen. Specificity was confirmed by dot blot. Anti-IL-1Ra IgG were affinity-purified from a high-titer patient and characterized by ELISA and SDS-PAGE. Epitope mapping was performed using phage display peptide libraries, followed by sequence alignment and structural mapping onto native IL-1Ra. Results: Anti-IL-1Ra antibody levels were significantly higher in AOSD patients than in healthy controls (p=0.003), with a greater proportion showing high titers (p<0.001). Levels did not differ between active and inactive AOSD patients. Purified antibodies displayed specific dose-dependent binding to IL-1Ra. Phage display identified two peptide motifs corresponding to linear epitopes mapped to surface-exposed regions of the native protein, indicating recognition of unmodified IL-1Ra domains. Conclusions: Anti-IL-1Ra antibodies are detectable in IL-1 inhibitor-naïve AOSD patients using a standardized ELISA. The identification of distinct linear epitopes suggests a heterogeneous autoimmune response targeting IL-1Ra and may support a role for adaptive immunity within the Still's disease spectrum. Further studies are needed to define their functional and clinical relevance.
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