Pediatric Rheumatology Online Journal → July 2003 → Vasculitides → Kawasaki Disease → Abstract #133

NEUTROPHIL DERIVED S100A12 (EN-RAGE) IS A POTENT SERUM MARKER FOR THE DISEASE ACTIVITY OF KAWASAKI DISEASE

D. Foell,¹ F. Ichida,² T. Vogl,³ C. Sorg,³ J. Roth.¹

Department of Pediatrics, University of Muenster, Muenster, Germany; ²Department of Pediatrics, Medical and Pharmaceutical University, Toyama, Japan; ³Institute of Experimental Dermatology, University of Muenster, Muenster, Germany

Background: S100A12 exhibits pro-inflammatory properties via interaction with the multiligand receptor for advanced glycation end products (RAGE). Blocking of S100A12 revealed promising therapeutic effects in different murine models of inflammation. The aim of our study was to investigate S100A12 in Kawasaki disease, and to follow up its serum levels for monitoring disease activity.
Methods: Normal S100A12 serum concentrations were determined in 47 healthy controls. S100A12 and C-reactive protein (CRP) levels were followed-up in 31 patients fulfilling the criteria of Kawasaki disease, who were treated with intravenous gammaglobulin (2 g/kg body weight over 1-5 days). Serum samples were obtained before start of therapy, within 24 hours after finishing treatment with gammaglobulin, after 2 weeks (10-18 days), and after 1 month (24-30 days).
Results: Two patients with coronary artery lesions and one patient without cardiac complications did not respond to initial therapy and were successfully re-treated with gammaglobulin. Before start of therapy, 29/31 patients (94%) with Kawasaki disease had S100A12 levels above the normal range (mean + 2 times SD of healthy controls; 120 ng/ml). In the group of responders the mean initial S100A12 level decreased significantly from 463 ng/ml (SD ±316) to 184 ng/ml (±147) within 24 hours after gammaglobulin treatment. In three patients with non-response to initial treatment S100A12 serum levels rather increased than decreased after gammaglobulin treatment. After responding to re-treatment S100A12 decreased and reached a normal level in all patients after 1 month. In all patients the decrease of S100A12 was associated with subsiding signs of acute vasculitis, i.e. fever and skin rash.
Conclusions: The present study indicates that S100A12 is a potent marker for Kawasaki disease. Since the interaction of S100A12 with multiligand receptors plays a key role in inflammatory responses, this protein may serve as novel target for future therapeutic interventions.