Full Papers
Serum cytokine profiling identifies distinct immune phenotypes in eosinophilic granulomatosis with polyangiitis: interleukin-25- and interleukin-5-driven eosinophilic subtypes
Y. Kamata1, H. Kusaka2, S. Yamamoto3, C. Hayashi4, T. Sato5, K. Sato6
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan. satok@jichi.ac.jp
CER19615
Full Papers
Received: 12/12/2025
Accepted : 23/02/2026
In Press: 22/10/2026
Abstract
OBJECTIVES:
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterised by eosinophilia and small vessel inflammation; however, its immunopathology remains incompletely understood. We aimed to elucidate immune dysregulation in EGPA by profiling serum cytokines in treatment-naïve patients in comparison with systemic lupus erythematosus (SLE), and by longitudinally assessing cytokine dynamics before and after initial therapy as well as during mepolizumab treatment.
METHODS:
We quantitatively profiled 31 serum cytokines in 27 patients with EGPA, including treatment-naïve and mepolizumab-treated individuals, and compared the results with those of 26 patients with active SLE. Longitudinal cytokine changes were assessed before and after initial therapy and during mepolizumab treatment. Eosinophil functional assays and quantification of alarmins were also performed.
RESULTS:
Patients with EGPA exhibited higher levels of Th2 cytokines, particularly IL-5, than those with SLE, whereas Th1 and Th17 cytokine levels were comparable. IL-1 receptor antagonist (IL-1Ra) levels were markedly elevated in EGPA, but not in peripheral eosinophils in vitro. Both IL-1Ra and IL-8 levels decreased after the initial treatment, suggesting their potential as biomarkers of disease activity. Subgroup analysis suggested heterogeneous eosinophilic patterns: one associated with IL-25, and the other with IL-5 in the absence of IL-25.
CONCLUSIONS:
EGPA exhibits heterogeneous and exploratory immunopathological patterns associated with IL-25 detectability or IL-5-associated eosinophilia. These findings provide novel insights into the pathogenesis of EGPA and highlight the potential of cytokine-based stratification for prospective personalised therapeutic approaches.
