Bouayad A. Interleukin-1 receptor antagonist autoantibodies in Still’s disease: Mechanistic insights and laboratory testing. World J Methodol 2026; 16(2): 114269 [DOI: 10.5662/wjm.v16.i2.114269]
Corresponding Author of This Article
Abdellatif Bouayad, MD, Associate Professor, Department of Immunology, Mohammed First University, Faculty of Medicine and Pharmacy Oujda, 4867 Oujda l’Université, Oujda-Angad 4867, Oriental, Morocco. a.bouayad@ump.ac.ma
Research Domain of This Article
Immunology
Article-Type of This Article
Minireviews
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World J Methodol. Jun 20, 2026; 16(2): 114269 Published online Jun 20, 2026. doi: 10.5662/wjm.v16.i2.114269
Interleukin-1 receptor antagonist autoantibodies in Still’s disease: Mechanistic insights and laboratory testing
Abdellatif Bouayad
Abdellatif Bouayad, Department of Immunology, Mohammed First University, Faculty of Medicine and Pharmacy Oujda, Oujda-Angad 4867, Oriental, Morocco
Author contributions: Bouayad A wrote and designed the minireview.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Abdellatif Bouayad, MD, Associate Professor, Department of Immunology, Mohammed First University, Faculty of Medicine and Pharmacy Oujda, 4867 Oujda l’Université, Oujda-Angad 4867, Oriental, Morocco. a.bouayad@ump.ac.ma
Received: September 15, 2025 Revised: October 13, 2025 Accepted: January 7, 2026 Published online: June 20, 2026 Processing time: 220 Days and 14.2 Hours
Abstract
Neutralizing autoantibodies against interleukin-1 receptor antagonist (IL-1RA) have been identified in patients with Still’s disease, often in association with hyperphosphorylation of the endogenous soluble IL-1RA protein. Although several cytokines and signaling pathways have been implicated in the pathogenesis of Still’s disease, the mechanisms underlying anti-IL-1RA autoantibody production remain unclear. Their detection is challenging due to assay heterogeneity, and therefore, a combination of different detection methods is recommended. This minireview explores potential predisposing factors for IL-1RA autoantibody development and discusses their biological and clinical significance. It also summarizes current diagnostic approaches for their detection, highlighting key challenges, pitfalls, and limitations.
Core Tip: Still’s disease is a rare, severe systemic inflammatory disorder characterized by elevated levels of neutralizing interleukin-1 receptor antagonist autoantibodies. Their induction is thought to result from a combination of host-related factors, such as human leukocyte antigen class II alleles, and interleukin-1 receptor antagonist intrinsic factors, including hyperphosphorylation. Despite frequent detection of these antibodies using immunoassays and functional cell-based assays, the lack of assay standardization limits their clinical utility. At present, their presence is best regarded as a marker of underlying immune dysregulation rather than a direct pathogenic driver.
