RMD Open (May 2025)

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

  • ,
  • Bruno Fautrel,
  • David Saadoun,
  • Tadej Avcin,
  • Thierry Martin,
  • Eric Hachulla,
  • Cem Gabay,
  • Seza Ozen,
  • Stéphanie Humblet-Baron,
  • Carine Wouters,
  • Adrian Liston,
  • Umut Kalyoncu,
  • Jordi Antón,
  • Sinisa Savic,
  • Yvan Jamilloux,
  • Christoph Kessel,
  • Dirk Foell,
  • Jeroen Raes,
  • Michael Hofer,
  • Luca Cantarini,
  • Isabelle Kone-Paut,
  • Søren Brunak,
  • Marie-Elise Truchetet,
  • Steven Vanderschueren,
  • Alexandre Belot,
  • Antonella Insalaco,
  • Haner Direskeneli,
  • Irina Giurgea,
  • Sophie Georgin-Lavialle,
  • Serge Amselem,
  • Léa Savey,
  • Pierre Quartier,
  • Anne Boland,
  • Jean-François Deleuze,
  • Sabrina Carpentier,
  • Katerina Laskari,
  • Thomas Henry,
  • Jean-David Bouaziz,
  • Clementien Vermont,
  • Emanuele Bizzi,
  • Helen Lachmann,
  • Nicolas Poursac,
  • Gilles Hayem,
  • Stéphane Mitrovic,
  • Patrick Matthys,
  • Isabella Friis Jørgensen,
  • Emiliana Rodriguez,
  • Philippe Hupé,
  • Paolo Sfriso,
  • Evangelos Andreakos,
  • Antoine Néel,
  • Alina Boteanu,
  • Sara Garcia,
  • Perrine Dusser,
  • Yvonne M Mueller,
  • Peter D Katsikis,
  • Matheus Vieira,
  • Charlotte Girard-Guyonvarc’h,
  • Charlotte Girard,
  • Assunta Caruso,
  • Violeta Bittermann,
  • Sonia Caccia,
  • Arturo Hernandez Cervantes,
  • Emna Chabaane,
  • Fanny Coffin,
  • Dominique de Seny,
  • Henri de Soyres,
  • Marc Dubourdeau,
  • Stefan J Erkeland,
  • Dimitrios I. Fotiadis,
  • Apolline Gallois,
  • Mieke Gouwy,
  • Sonia Karabina,
  • Andres Jimenez Kaufmann,
  • Keshia Koutekissa,
  • Karoline Krause,
  • Thibault Mahevas,
  • Nasima Matsa,
  • Michael F. McDermott,
  • Aura Moreno Vega,
  • Marco Francesco Natale,
  • Maria Papadaki,
  • Costas Papaloukas,
  • Christophe Poulet,
  • Sebastian Proost,
  • Paul Proost,
  • Julien Roméjon,
  • Sarhan Yaiche,
  • Savvas Savvides,
  • Vassili Soumelis,
  • Sigrid Swagemakers,
  • Paul Van Daele,
  • Harmen J. G. vandeWerken,
  • Peter van derSpek,
  • Rogier van Wijck

DOI
https://doi.org/10.1136/rmdopen-2024-005388
Journal volume & issue
Vol. 11, no. 2

Abstract

Read online

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.