Interleukin-1 receptor antagonist autoantibodies in Still’s disease: Mechanistic insights and laboratory testing

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.