Differences in GlycA and lipoprotein particle parameters may help distinguish acute kawasaki disease from other febrile illnesses in children

Abstract

Background: Glycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction. The response of acute Kawasaki disease (KD) patients to IVIG treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Additionally, the distribution and function of lipoprotein particles are altered during inflammation. Therefore, the aim of this study was to explore the potential for GlycA, a marker of protein glycosylation, and the lipoprotein particle profile to distinguish pediatric patients with acute KD from those with other febrile illnesses.

Methods: Nuclear magnetic resonance was used to quantify GlycA and lipoprotein particle classes and subclasses in pediatric subjects with acute KD (n = 75), post-treatment subacute (n = 36) and convalescent (n = 63) KD, as well as febrile controls (n = 48), and age-similar healthy controls (n = 48).

Results: GlycA was elevated in acute KD subjects compared to febrile controls with bacterial or viral infections, IVIG-treated subacute and convalescent KD subjects, and healthy children (P <0.0001). Acute KD subjects had increased total and small low density lipoprotein particle numbers (LDL-P) (P <0.0001) and decreased total high density lipoprotein particle number (HDL-P) (P <0.0001) compared to febrile controls. Consequently, the ratio of LDL-P to HDL-P was higher in acute KD subjects than all groups tested (P <0.0001). While GlycA, CRP, erythrocyte sedimentation rate, LDL-P and LDL-P/HDL-P ratio were able to distinguish patients with KD from those with other febrile illnesses (AUC = 0.789-0.884), the combinations of GlycA and LDL-P (AUC = 0.909) or GlycA and the LDL-P/HDL-P ratio (AUC = 0.910) were best at discerning KD in patients 6-10 days after illness onset.

Conclusions: High levels of GlycA confirm enhanced protein glycosylation as part of the acute phase response in KD patients. When combined with common laboratory tests and clinical characteristics, GlycA and NMR-measured lipoprotein particle parameters may be useful for distinguishing acute KD from bacterial or viral illnesses in pediatric patients.

Keywords: Biomarkers; GlycA; Kawasaki disease; Lipoprotein particle number.

Fig. 1

Plasma concentrations of GlycA (μmol/L) among patients with: acute, subacute, early and late convalescent KD patients, febrile controls of bacterial and viral origin, and healthy controls. KD subjects are identified by coronary artery status: normal acute echocardiogram (solid black symbol); CAA (open symbol); or dilated coronary artery (solid gray symbol). Horizontal bars represent median and interquartile range

Fig. 2

a) Total HDL-P, b) total LDL-P and c) the ratio of total LDL-P to total HDL-P among acute, subacute, early and late convalescent KD patients, febrile controls of bacterial and viral origin, and healthy controls. Horizontal bars represent median and interquartile range

Fig. 3

Time course of biomarkers (median) in KD subjects from acute phase to early convalescence: a) GlycA (left y-axis; black line and symbols) and CRP (right y-axis; dark gray line and symbols), b) LDL-P/HDL-P ratio (left y-axis; black line and symbols) and CRP (right y-axis; dark gray line and symbols), c), GlycA (left y-axis; black line and symbols) and ESR (right y-axis; dark gray line and symbols), d) LDL-P/HDL-P ratio (left y-axis; black line and symbols) and ESR (right y-axis; dark gray line and symbols) in KD patients plotted as a function of illness day (Illness day 1 = first day of fever). Illness day 1 = first day of fever. Pre-IVIG treatment = days 2–10 and post-IVIG treatment = days 13–24

Fig. 4

ROC curves for the discrimination of KD from febrile illnesses during illness days 6–10 by CRP, ESR, GlycA, LDL-P/HDL-P, GlycA and LDL-P/HDL-P and GlycA + LDL-P