Deutscher Rheumatologiekongress 2026
Age-dependent diagnostic value of phagocyte-specific S100 proteins in Still’s disease
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Introduction: Still’s disease (SD) is a rare systemic autoinflammatory disease (SAID) with pediatric or adult onset. Clinical overlap with other SAIDs, including fever, rash, and serositis, often delays diagnosis and targeted treatment. Recently, the EULAR/PReS guidelines for the diagnosis and management of SD recommended using phagocyte-specific S100 proteins (S100A8/A9, S100A12) as diagnostic biomarkers [1]. However, few studies have directly compared their performance across a broader age range. Here, we evaluate the ability of S100 proteins to differentiate pediatric SD and adult SD from other SAIDs.
Methods: Using identical biomarker assay platforms, we analyzed serum levels of S100A8/A9 and S100A12 in 334 patients with active SAIDs and 61 healthy controls. This included 78 pediatric and 46 adult SD patients from the European ImmunAID and a multicenter German cohort.
Results: S100 protein levels were elevated in SD patients when compared to other SAID patients and healthy controls. In adult SD, S100A8/A9 and S100A12 correlated with established inflammatory mediators, including ferritin (r=0.413 and r=0.367), interleukin-6 (IL-6) (r=0.636 and r=0.639) and leukocyte count (r=0.804 and r=0.796). In pediatric SD, correlations with ferritin were similar (r=0.362 and r=0.373) but weak for IL-6 (r=0.266 and r=0.255) and leukocyte count (r=0.335 and r=0.312). Furthermore, longitudinal analysis demonstrated a significant decrease in S100 protein levels in SD patients under treatment (P<0.01).
Interestingly, S100A8/A9 and S100A12 serum levels were significantly higher in pediatric (median=71,675 ng/mL and 1,240 ng/mL) compared to adult SD patients (median=24,237 ng/mL and 302.5 ng/mL; P<0.001). These findings were supported by negative correlations between S100 protein levels and patient age (r=-0.370 and r=-0.417). Receiver operating characteristic (ROC) analyses confirmed strong diagnostic performance for S100A8/A9 and S100A12 in pediatric SD (AUC 0.872 and 0.879), whereas discrimination in adult SD was limited (AUC 0.722 and 0.705).
Conclusion: This study demonstrates that while S100 proteins are elevated in SD compared with other SAIDs, their expression differs between pediatric and adult patients. While these findings do not challenge the concept that pediatric and adult SD represent a single disease spectrum [1], our data strongly argue for age-adapted use of S100 protein-based diagnostics and respective cut-offs to optimize diagnostic accuracy and disease management.
Disclosures: COI statement: HW has received honoraria (lecture fees) from Novartis and Takeda, and travel support from Octapharma and CSL-Behring. CH received speaker fees and travel support from Pfizer. CK has received consulting fees from Novartis and Swedish Orphan Biovitrum (SOBI), speaker fees from SOBI and research support from Novartis. DF received speaker fees/honoraria from Chugai-Roche, Novartis and SOBI as well as research support from Novartis, Pfizer and SOBI. No other disclosures relevant to this article were reported.
Sources of support: EV received support from an intramural funding program of Muenster University medical faculty for innovative medical research (IMF, grant number VE112304). CK receives support from the German Research Foundation (DFG, grant number KE 2026 1/3). This study was supported by funds obtained within the H2020 EU-program under grant agreement no 779295 (ImmunAID) to DF as part of the ImmunAID consortium.
The ImmunAID consortium: Zohra Aknouche, Serge Amselem, Evangelos Andreakos, Jordi Anton, Tadej Avcin, Alexandre Belot, Violeta Bittermann, Emanuele Bizzi, Anne Boland, Alina Boteanu, Jean-David Bouaziz, Søren Brunak, Sonia Caccia, Etienne Camenen, Luca Cantarini, Sabrina Carpentier, Emna Chabaane, Fanny Coffin, Dominique de Seny, Henri de Soyres, Jean-François Deleuze, Haner Direskeneli, Marc Dubourdeau, Perrine Dusser, Stefan J Erkeland, Bruno Fautrel, Dirk Foell, Dimitrios I. Fotiadis, Isabella Friis Jørgensen, Cem Gabay, Apolline Gallois, Sophie Georgin-Lavialle, Charlotte Girard, Irina Giurgea, Mieke Gouwy, Eric Hachulla, Gilles Hayem, Thomas Henry, Arturo Hernandez Cervantes, Stephanie Humblet-Baron, Philippe Hupé, Antonella Insalaco, Yvan Jamilloux, Umut Kalyoncu, Sonia Karabina, Peter D Katsikis, Christoph Kessel, Isabelle Koné-Paut, Karoline Krause, Helen Lachmann, Katerina Laskari, Adrian Liston, Thibault Mahevas, Thierry Martin, Nasima Matsa, Patrick Matthys, Michael F. McDermott, Stephane Mitrovic, Aura Moreno Vega, Yvonne M Mueller, Marco Francesco Natale, Antoine Néel, Seza Ozen, Maria Papadaki, Costas Papaloukas, Christophe Poulet, Nicolas Poursac, Sebastian Proost, Paul Proost, Pierre Quartier, Jeroen Raes, Julien Roméjon, David Saadoun, Léa Savey, Sinisa Savic, Savvas Savvides, Paolo Sfriso, Vassili Soumelis, Marie-Elise Truchetet, Paul Van Daele, Harmen J. G. van de Werken, Peter van der Spek, Steven Vanderschueren, Clementien Vermont, Matheus Vieira, Carine Wouters, Sarhan Yaiche, Zhicheng Zhou
