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Neutrophil-derived S100A12 as novel biomarker of inflammation in Familial Mediterranean Fever
  1. Tilmann Kallinich (tilmann.kallinich{at}charite.de)
  1. Pediatric Pneumology and Immunology, Charite University Hospital Berlin, Germany
    1. Helmut Wittkowski
    1. Department of Pediatrics, University of Muenster, Muenster, Germany
      1. Rolf Keitzer
      1. Pediatric Pneumology and Immunology, Charite University Hospital Berlin, Germany
        1. Johannes Roth
        1. Institute of Immunology, University of Muenster, Muenster, Germany
          1. Dirk Foell
          1. Department of Pediatrics, University of Muenster, Muenster, Germany

            Abstract

            Objective: Familial Mediterranean Fever (FMF) is characterized 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 the 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 categorized 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 colchicine treated patients with persistent symptoms (mean „b SEM, 6260 „b 2120 ng/ml) than in those with clinically controlled disease (440 „b 80 ng/ml, p < 0.001). In contrast to classical markers of inflammation, S100A12 was significantly elevated in clinically unaffected homozygous MEFV 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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