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Elevated serum levels of interleukin-18 discriminate Still’s disease from other autoinflammatory conditions: results from the European ImmunAID cohort

1 Apr 2025RMD Open

DOI : 10.1136/rmdopen-2024-005388

Authors

Charlotte Girard-Guyonvarc’h, Emiliana Rodriguez, Yvonne M Mueller, Assunta Caruso, Peter D Katsikis, Cem Gabay

Abstract

Objectives

Systemic autoinflammatory diseases (SAIDs) represent a set of conditions with exaggerated innate immune responses. IL-1β and IL-18 are key cytokines involved in the pathogenesis of some SAID. We aimed to assess the diagnostic value of serum levels of IL-1β, IL-18, their respective inhibitors IL-1Ra and IL-18 binding protein (IL-18BP), and IFN-γ in SAID.

Methods

A cohort of patients with active SAID, including monogenic (mSAID) and genetically undiagnosed SAID (guSAID) from different European countries, with active disease at inclusion, was established. Serum levels of cytokines were measured by immunoassays.

Results

Sera from 53 mSAID, 220 guSAID and 49 controls without inflammatory disease were analysed. Serum levels of total and free IL-18 were significantly increased in Still’s disease in comparison to most SAID and non-inflammatory controls. Levels of total IL-18 were also elevated in patients with familial Mediterranean fever to a comparable extent as in Still’s disease. In contrast, free IL-18 levels were selectively higher in Still’s disease. Receiver operating characteristic curve analysis showed that total IL-18 was the most sensitive and specific marker for the diagnosis of Still’s disease (area under the curve=0.91). There was a positive correlation between IL-18 and ferritin. In 10 patients with Still’s disease who had a second blood collection, we found a significant decrease in serum levels of free IL-18 after treatment.

Conclusions

Our results show that IL-18 can discriminate Still’s disease from other SAID, and free IL-18 levels may be relevant to assess response to therapy in these patients.

Members

FANNY COFFIN

Ingénieur de recherche Inserm

JULIEN ROMEJON

Ingénieur de recherche

HENRI DE SOYRES

Ingénieur d'études

APOLLINE GALLOIS

Ingénieur de recherche
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AMNA CHABAANE MANFROI

Ingénieur de recherche