Abstract 98: Tenascin-C as a Novel Biomarker for Predicting Therapeutic Effect in Kawasaki Disease

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Abstract

Background: In acute stage of Kawasaki disease (KD), patients who are unresponsive to initial therapy are immediately administered additional therapy to prevent the development of coronary artery abnormalities (CAAs). Although failure to respond is defined as persistent or recrudescent fever after treatment, it is difficult to recognize the presence of fever because steroids are administered with intravenous immunoglobulin (IVIG) in severe KD patients in Japan. In addition, inflammatory markers such as CRP usually decrease after initial therapy in patients who are unresponsive to initial therapy and there is no biomarker for monitoring treatment effect. Tenascin-C (TN-C) is an extracellular matrix protein specifically upregulated in response to tissue injury and inflammation.

Methods: We recruited 174 patients (male 102, female 72) from August 2011 to April 2014, from fourteen institutions in Japan. Serum levels of TN-C (sTN-C) were examined using ELISA before and after initial treatment. The initial treatments consisted of: 30 aspirin only, 111 IVIG + aspirin, and 33 IVIG + aspirin + prednisolone. We compared patients who responded to initial therapy (R group; n = 134) with those who did not respond (NR group; n = 40) regarding patient profile and laboratory data.

Results: Patients in NR group had higher % neutrophil (p = 0.004), CRP (p = 0.012) and sTN-C (p = 0.049) than in R group before treatment. After initial therapy, WBC, % neutrophil and CRP significantly decreased in both groups (p < 0.001), but sTN-C did not significantly decrease in NR group (p = 0.485). When sTN-C after initial therapy was used to predict unresponsiveness of initial therapy, sensitivity, specificity and AUC were 85%, 55%, and 0.745 respectively. Especially in patients who were administered steroids with IVIG as initial therapy, the accuracy of predictive model using sTN-C after initial therapy was high (AUC 0.812, sensitivity 71%, specificity 81%). The incidence of CAAs tends to be higher in NR group than in R group (12.5 vs. 3.7 %, p = 0.051).

Conclusions: TN-C is a potential biomarker in predicting the need for additional therapy. Especially in KD patients who are treated by steroids with IVIG, TN-C may be useful.

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