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

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 used to analyze PBMC subsets and identify treatment response-related transcriptomic signatures. 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 modulated the adaptive immune response, suppressing naïve B cell activity, enhancing circulating plasma cell precursor activity, and significantly altering γδ T cell and mucosal-associated invariant T cell populations. In conclusion, goflikicept effectively normalized dysregulated immune responses in IRP, suggesting a novel therapeutic approach for NLRP3-mediated 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.