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Identification of candidate diagnostic serum biomarkers for Kawasaki disease using proteomic analysis
Yayoi Kimura1, Masakatsu Yanagimachi2,3, Yoko Ino1
1Advanced Medical Research Center, Yokohama City University, Yokohama, Japan.
Insights
Researchers identified key serum proteins, including leucine-rich alpha-2-glycoprotein (LRG1), that change during acute Kawasaki disease (KD). These findings may help diagnose KD more effectively, aiding early cardiovascular complication management.
Area of Science:
- Biochemistry
- Immunology
- Pediatrics
Background:
- Kawasaki disease (KD) is a childhood febrile illness causing systemic vasculitis and potential cardiovascular complications.
- Diagnosing KD relies on clinical symptoms, often leading to diagnostic challenges.
- Identifying reliable biomarkers is crucial for early and accurate KD diagnosis.
Purpose of the Study:
- To identify novel serum protein biomarkers for Kawasaki disease (KD).
- To differentiate protein expression profiles between acute and recovery phases of KD.
- To validate potential biomarkers for clinical diagnostic utility.
Main Methods:
- Proteomic analysis using mass spectrometry (MS) on serum samples from two KD patients.
- Quantification of 1,879 identified proteins.
- Validation of differential protein expression using western blot and microarray enzyme-linked immunosorbent assays (ELISAs) on 270 samples.
Main Results:
- Three proteins—lipopolysaccharide-binding protein (LBP), leucine-rich alpha-2-glycoprotein (LRG1), and angiotensinogen (AGT)—showed elevated levels in the acute phase of KD.
- Retinol-binding protein 4 (RBP4) levels were decreased during the acute phase.
- LRG1 expression was specifically altered in the acute phase of KD, distinguishing it from recovery phase and other febrile illnesses.
Conclusions:
- Leucine-rich alpha-2-glycoprotein (LRG1) demonstrates potential as a diagnostic biomarker for Kawasaki disease (KD).
- These identified proteins may aid in the definitive diagnosis of KD, complementing clinical assessments.
- Further validation could lead to improved diagnostic strategies for KD and prevention of cardiac sequelae.
Abstract:
Kawasaki disease (KD) is a systemic vasculitis and childhood febrile disease that can lead to cardiovascular complications. The diagnosis of KD depends on its clinical features, and thus it is sometimes difficult to make a definitive diagnosis. In order to identify diagnostic serum biomarkers for KD, we explored serum KD-related proteins, which differentially expressed during the acute and recovery phases of two patients by mass spectrometry (MS). We identified a total of 1,879 proteins by MS-based proteomic analysis. The levels of three of these proteins, namely lipopolysaccharide-binding protein (LBP), leucine-rich alpha-2-glycoprotein (LRG1), and angiotensinogen (AGT), were higher in acute phase patients. In contrast, the level of retinol-binding protein 4 (RBP4) was decreased. To confirm the usefulness of these proteins as biomarkers, we analyzed a total of 270 samples, including those collected from 55 patients with acute phase KD, by using western blot analysis and microarray enzyme-linked immunosorbent assays (ELISAs). Over the course of this experiment, we determined that the expression level of these proteins changes specifically in the acute phase of KD, rather than the recovery phase of KD or other febrile illness. Thus, LRG1 could be used as biomarkers to facilitate KD diagnosis based on clinical features.
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