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Neutrophil-derived S100A12 as novel biomarker of inflammation in familial Mediterranean fever
  1. Tilmann Kallinich1,
  2. Helmut Wittkowski2,
  3. Rolf Keitzer1,
  4. Johannes Roth2,3,
  5. Dirk Foell2
  1. 1Pediatric Pneumology and Immunology, Charite University Hospital Berlin, Berlin, Germany
  2. 2Department of Pediatrics, University of Muenster, Muenster, Germany
  3. 3Institute of Immunology, University of Muenster, Muenster, Germany
  1. Correspondence to Tilmann Kallinich, Department of Pediatric Pneumology and Immunology, Charité–Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; tilmann.kallinich{at}


Objective Familial Mediterranean fever (FMF) is characterised by recurrent periodic febrile attacks and persistent subclinical inflammation. The damage-associated molecular pattern (DAMP) protein S100A12 has proven to be a sensitive marker for disease activity and inflammation in numerous inflammatory disorders. The aim of this study was to analyse the role of S100A12 in the detection of inflammation in patients with FMF.

Methods 52 children and adolescents with a clinical and/or genetic diagnosis of FMF were prospectively followed-up over 18 months (in total 196 visits). During clinical visits, erythrocyte sedimentation rate, C reactive protein, serum amyloid A and S100A12 serum concentrations were determined. Patients were categorised into four groups according to the clinical activity of FMF.

Results Serum concentrations of S100A12 were excessively increased in patients with a mean increase of about 290-fold in active FMF above normal controls. S100A12 decreased significantly after introduction of colchicine therapy. Serum concentrations of S100A12 were significantly higher in patients treated with colchicine with persistent symptoms (mean±SEM, 6260±2120 ng/ml) than in those with clinically controlled disease (440±80 ng/ml, p<0.001). In contrast to classical markers of inflammation, S100A12 was significantly elevated in clinically unaffected homozygous MEFV gene mutation carriers, indicating subclinical inflammation.

Conclusions S100A12 is a valuable biomarker for monitoring disease activity, inflammation and response to colchicine treatment in patients with FMF. It might even be more sensitive in detecting subclinical inflammation than other available indicators.

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  • TK and HW contributed equally to this work.

  • Funding The study was supported by grants of the Interdisciplinary Centre for Clinical Research, University of Muenster, Germany (Project Foe2/005/06), the German Research Foundation (DFG Project FO 354/2–2) and of the German Ministry of Education and Research (BMBF, project ‘AID-NET’). The funding sources had no involvement in the study design; in the collection, analysis and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.

  • Competing interests JR has a pending patent application for S100A12 ELISA (US 20030175713). All other authors declare that they have no financial or personal competing interest related to this study.

  • Ethics approval This study was conducted with the approval of the University Muenster.

  • Provenance and peer review Not commissioned; externally peer reviewed.