Single-cell RNA profiling suggests goflikicept-mediated immune modulation in idiopathic recurrent pericarditis.

OBJECTIVE: Idiopathic recurrent pericarditis (IRP) is a rare autoinflammatory disorder characterized by NLRP3 inflammasome overactivation, resulting in excessive IL-1β and IL-1α production. Although IL-1 blockade shows promise as a therapeutic strategy, the underlying molecular mechanisms remain incompletely understood. We investigated the effect of goflikicept, a novel heterodimeric fusion protein that inhibits both IL-1β and IL-1α, on peripheral blood mononuclear cell (PBMC) transcriptomes from patients with IRP. METHODS: Single‑cell RNA sequencing was performed on PBMCs from patients with IRP before and during goflikicept treatment. Treatment‑related transcriptomic signatures were analyzed across innate and adaptive immune cell subsets. RESULTS: Goflikicept induced temporal transcriptional reprogramming, with a particularly pronounced downregulation of IL-1-related inflammatory pathways in classical monocytes by day 35 of treatment. Furthermore, goflikicept was associated with coordinated transcriptional changes in adaptive immune compartments, including naïve B cells, circulating plasma cell precursors, and unconventional T cell subsets (γδ T and MAIT cells). CONCLUSIONS: Goflikicept effectively normalized dysregulated immune responses in IRP, supporting the broader therapeutic potential of IL-1 blockade in NLRP3-mediated inflammatory diseases. This study provides the first single-cell resolution insights into the molecular mechanisms of IL-1 blockade, informing the development of targeted therapies for autoinflammatory conditions.