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

Abstract

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. 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. 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). 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.