Goflikicept induced temporal transcriptional reprogramming in PBMCs from IRP patients, with pronounced downregulation of IL-1-related inflammatory pathways in classical monocytes and coordinated changes in adaptive immune compartments, providing the first single-cell resolution insights into the molecular mechanisms of IL-1 blockade in idiopathic recurrent pericarditis.
Key Findings
Results
Goflikicept treatment induced temporal transcriptional reprogramming in peripheral blood mononuclear cells from IRP patients, with the most pronounced effects observed by day 35 of treatment.
Single-cell RNA sequencing was performed on PBMCs from IRP patients before and during goflikicept treatment
Treatment-related transcriptomic signatures were analyzed across both innate and adaptive immune cell subsets
The temporal nature of reprogramming suggests time-dependent modulation of immune responses
Goflikicept is described as a novel heterodimeric fusion protein that inhibits both IL-1β and IL-1α
Results
Classical monocytes showed particularly pronounced downregulation of IL-1-related inflammatory pathways following goflikicept treatment.
Downregulation of IL-1-related inflammatory pathways in classical monocytes was most evident by day 35 of treatment
IRP is characterized by NLRP3 inflammasome overactivation resulting in excessive IL-1β and IL-1α production
Classical monocytes were identified as a primary innate immune cell subset affected by goflikicept-mediated immune modulation
The findings implicate classical monocytes as a key cellular target of IL-1 blockade in IRP
Results
Goflikicept was associated with coordinated transcriptional changes in adaptive immune compartments, including naïve B cells, circulating plasma cell precursors, and unconventional T cell subsets.
Affected adaptive immune cell populations included naïve B cells and circulating plasma cell precursors
Unconventional T cell subsets specifically affected included γδ T cells and MAIT cells
These changes represent coordinated transcriptional responses across multiple adaptive immune compartments
This extends the known effects of IL-1 blockade beyond innate immunity to adaptive immune regulation
Results
Goflikicept effectively normalized dysregulated immune responses in IRP patients.
Normalization was observed at the transcriptomic level across multiple immune cell subsets
The drug targets both IL-1β and IL-1α as a heterodimeric fusion protein, distinguishing it from single-cytokine blockers
Findings support the broader therapeutic potential of IL-1 blockade in NLRP3-mediated inflammatory diseases
This is described as the first study to provide single-cell resolution insights into the molecular mechanisms of IL-1 blockade in this condition
Background
IRP is characterized by NLRP3 inflammasome overactivation resulting in excessive IL-1β and IL-1α production, which is the mechanistic basis for goflikicept therapy.
IRP is classified as a rare autoinflammatory disorder
NLRP3 inflammasome overactivation drives both IL-1β and IL-1α overproduction in this condition
IL-1 blockade was identified as a promising therapeutic strategy for IRP
The underlying molecular mechanisms of IL-1 blockade in IRP were described as incompletely understood prior to this study
What This Means
This research suggests that goflikicept, a new drug that blocks two inflammatory proteins (IL-1β and IL-1α), changes the activity of multiple immune cell types in patients with idiopathic recurrent pericarditis (IRP), a rare condition where the sac around the heart becomes repeatedly inflamed. By analyzing individual immune cells from patient blood samples before and during treatment using a technique called single-cell RNA sequencing, the researchers were able to see exactly which types of immune cells were affected and how their gene activity changed. The most significant changes were seen in a type of innate immune cell called classical monocytes, where inflammation-related genes were strongly turned down after 35 days of treatment.
The study also found that the drug's effects extended beyond the initial immune response cells to also affect more specialized immune cells involved in longer-term immunity, including certain B cells (which make antibodies), plasma cell precursors, and two unusual types of T cells (γδ T cells and MAIT cells). This suggests that blocking IL-1 has broader effects on the immune system than previously appreciated, reshaping both the rapid 'first responder' immune cells and the more specialized adaptive immune cells.
This research matters because it provides the first detailed, cell-by-cell picture of how IL-1 blocking therapy works at the molecular level in IRP. This kind of detailed understanding could help doctors better predict which patients might respond to such treatments and could guide the development of new therapies for IRP and other inflammatory diseases driven by similar mechanisms, such as those involving the NLRP3 inflammasome pathway.
Golovkin A, Markelova E, Ignatieva E, Kalinina O, Ivanova O, Antonets D, et al.. (2026). Single-cell RNA profiling suggests goflikicept-mediated immune modulation in idiopathic recurrent pericarditis.. Inflammation research : official journal of the European Histamine Research Society ... [et al.]. https://doi.org/10.1007/s00011-026-02347-x