Monitoring of the serum proteome in Kawasaki disease patients before and after immunoglobulin therapy

Kawasaki disease (KD) is a systemic vasculitis that mainly affects children younger than 5 years. The causal pathogen is unknown, therefore specific diagnostic biomarkers and therapy are unavailable. High-dose intravenous immunoglobulin (IVIG) is considered as the most effective therapy to reduce the prevalence of coronary artery lesion (CAL) in KD; however, it has side effects. This study aimed to (1) determine whether IVIG therapy is effective at the molecular level; (2) provide the first serum proteomic profile of KD under IVIG therapy; and (3) screen for monitoring biomarker candidates. We extracted serum proteins from samples of healthy individuals and from KD patients before and after IVIG therapy, and employed two-dimensional electrophoresis and MALDI-TOF/TOF mass spectrometry to identify differentially expressed proteins. The identifications were validated by Western blotting. We identified 29 differentially expressed proteins in KD patients and found that IVIG therapy restored most of these proteins to near-normal levels. Tracing the protein levels of single patients before and after IVIG therapy showed that the proteins, especially Transthyretin (TTR), are potential markers for therapeutic monitoring. Functional analyses of these proteins by PANTHER and String suggested that the key influence of KD lay in the immune system, which was targeted by IVIG.