Abstract

BackgroundGlycosylation 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.MethodsNuclear 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).ResultsGlycA 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.ConclusionsHigh 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12887-016-0688-5) contains supplementary material, which is available to authorized users.

Highlights

  • Glycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction

  • GlycA levels were similar between healthy controls and convalescent Kawasaki disease (KD) patients, levels were higher in children with acute febrile illness and subacute KD than in healthy controls (P

  • GlycA levels did not differ between acute KD patients who were resistant and those who responded to intravenous immunoglobulin (IVIG) treatment (Additional file 2: Figure S2) or between acute KD subjects with coronary artery aneurysms (CAA) or dilated coronary arteries and those with normal echocardiograms (Fig. 1 and Additional file 2: Figure S2)

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Summary

Introduction

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. 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. Glycosylation patterns of serum and cell surface proteins are critical determinants of the immune response [17, 18], and response of acute KD patients to IVIG treatment has been linked to sialic acid levels on native IgG [19]. We hypothesized that GlycA levels are elevated in pediatric subjects with acute KD and serve as an indicator of acute inflammation

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