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

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.

Glycoprotein A as a biomarker of pulmonary infection and inflammation in children with cystic fibrosis

“…GlycA levels detected in each child from our CF population were at least double that reported in healthy children of a similar age and were quite similar to those seen in acute Kawasaki disease. 9 This may support the hypothesis that GlycA elevation in our cohort is a result of the inflammatory state associated with CF. As our subjects were young, extrapulmonary manifestations of CF such as diabetes and arthropathy that might themselves drive inflammation were not present.…”

“…GlycA is a novel blood biomarker that has been shown to be elevated in various inflammatory conditions in both adults and children. [7][8][9] In our study cohort of participants with CF, we demonstrated that GlycA levels were associated with the presence of proinflammatory organisms and/or detectable free NE in BAL fluid, as well as with BWT on CT imaging.…”

“…Glycoprotein A (GlycA) levels reflect the abundance of mobile N‐acetyl sugar groups found on glycoproteins in circulating blood which are involved in the human acute phase response . In a variety of inflammatory disease states ranging from diabetes, cancer, and atherosclerosis in adults to acute Kawasaki disease in children, GlycA levels are elevated. Furthermore, in preschool children GlycA is associated with white cell count elevation and granulocyte proportion more closely than high sensitivity C‐reactive protein is, suggesting that GlycA may be a superior marker of chronic cumulative inflammation in early life .…”

Title: Human Serum/Plasma Glycoprotein Analysis by 1H-NMR, an Emerging Method of Inflammatory Assessment

“…Takayasu arteritis N-Acetyl glycoproteins are significantly up-regulated in TA patients [129,130] Kawasaki disease High levels of GlycA were confirmed in paediatric population with acute KD disease [110]…”

“…In a pediatric population with acute KD disease, high levels of GlycA were confirmed. It was also found that GlycA and lipoproteins, both measured with 1 H-NMR, may be useful for distinguishing acute KD from bacterial or viral illnesses [110] but further research is needed.…”