Autoantibodies against interleukin-1 receptor antagonist in Still’s disease in adult patients, data from a multicenter cohort study
- 1Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila , ,
- 2Rheumatic and Systemic Autoimmune Diseases Unit, Department of Interdisciplinary Medicine, University of Bari Medical School , ,
- 3Fondazione Policlinico Universitario , ,
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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BibTeX
@article{ruscitti2026autoantibodies,
title = {{Autoantibodies against interleukin-1 receptor antagonist in Still’s disease in adult patients, data from a multicenter cohort study}},
author = {Piero Ruscitti and Elvira Favoino and Federica Viapiano and Giulia Sgarlata and Marta Vomero and Letizia Pia Di Corcia and Francesco Maria Mariani and Paola Cipriani and Roberto Giacomelli and Federico Perosa},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1957327},
url = {https://europepmc.org/article/PMC/PMC13672321},
note = {CC BY},
}
RIS
TY - JOUR
TI - Autoantibodies against interleukin-1 receptor antagonist in Still’s disease in adult patients, data from a multicenter cohort study
AU - Piero Ruscitti
AU - Elvira Favoino
AU - Federica Viapiano
AU - Giulia Sgarlata
AU - Marta Vomero
AU - Letizia Pia Di Corcia
AU - Francesco Maria Mariani
AU - Paola Cipriani
AU - Roberto Giacomelli
AU - Federico Perosa
PY - 2026
DA - 2026/10/02
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1957327
UR - https://europepmc.org/article/PMC/PMC13672321
AB - 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.
SN - 1664-3224
ER -