Table 3.

Proteomic biomarkers of Kawasaki disease.

Protein	Biological function	Caveats	Limitations	References
NT-pro BNP	Marker of myocardial damage; increased in response to cardiac dilatation and neuro-humoral factors	Higher values in CAAs and can predict IVIG resistance	Non-specific test • Can be elevated in other causes of diastolic dysfunction • Serum values vary with age	(38–44)
Suppression of tumorigenicity 2(sST2)	Member of the IL 1 receptor family and reflect cardiovascular stress and fibrosis	Elevated in acute stages of KD Correlate with impaired myocardial relaxation	Prognostic significance of sST2 levels in acute KD is unknown	(45)
Cardiac troponin I (cTnI)r	Marker of myocardial damage	Elevated in acute stages	Non-specific marker	(46, 47)
Periostin	Matricellular protein that plays a role in vascular and cardiac responses to injury	Upregulated 11-fold in acute and chronic KD coronary arteries	Non-specific	(48)
Gamma-glutamyl transferase(GGT) and Alanine transferase (ALT)	Biomarkers of cardiocyte inflammation	Increased in acute stages of KD	Non-specific	(45)
Clusterin	Component of high density lipoproteins; role in maintaining integrity of coronary endothelium	Values <12 mg/L associated with CAAs occurrence in KD patients	Need validation via larger studies	(49)
Thrombospondin (TSP-1 and TSP-2)	Involved in cardiovascular inflammation and maintaining the integrity and function of cardiac structures	• Elevated in acute KD • Associated with high risk of IVIg resistance	Need larger studies for validation	(50)
Fibrinogen beta and gamma chains	Cleavage products of fibrinogen and fibrin regulate systemic inflammation	Elevated in acute KD	Non-specific markers of inflammation	(49)
CD5 antigen-like precursor (CD5L)	Marker of acute inflammation	Increased in acute KD	Non-specific markers of inflammation	(49)
Nitric oxide synthases (iNOS)	NO has an important role in maintaining vascular tone and integrity of vessels	Correlate with the severity and progression of CAA	Non-specific marker of inflammation	(51)
Periostin	Matricellular protein of coronary endothelium	KD patients have significantly elevated serum values compared with febrile controls	Tissue based tests are difficult in clinical settings	(44)
Lipopolysaccharide-binding protein (LBP)	Markers of inflammation	Higher in acute KD	Need validation in larger studies	(52)
Leucine-rich alpha-2-glycoprotein (LRG1)	Markers of inflammation	Higher in acute KD	Need validation in larger studies	(52)
Angiotensinogen (AGT)	Markers of inflammation	Higher in acute KD	Need validation in larger studies	(52)
Tenacin- C	Extracellular matrix glycoprotein that is upregulated at sites of tissue injury and inflammation	Useful biomarker to predict the risk of developing CAAs and IVIg resistance	Need validation in larger studies	(53)
Urine protein markers: • Filamin • Talin • Complement regulator CSMD3 • Immune pattern recognition receptor muclin • Immune cytokine protease meprin A	Markers of inflammation	• Higher in acute KD • Non-invasive biomarkers of KD	Need validations via larger studies	(54)