Treatment Response in Kawasaki Disease Is Associated with Sialylation Levels of Endogenous but Not Therapeutic Intravenous Immunoglobulin G

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Treatment Response in Kawasaki Disease Is Associated with Sialylation Levels of Endogenous but Not Therapeutic Intravenous Immunoglobulin G
Title:
Treatment Response in Kawasaki Disease Is Associated with Sialylation Levels of Endogenous but Not Therapeutic Intravenous Immunoglobulin G
Journal Title:
PLoS ONE
Keywords:
Publication Date:
06 December 2013
Citation:
Ogata S, Shimizu C, Franco A, Touma R, Kanegaye JT, et al. (2013) Treatment Response in Kawasaki Disease Is Associated with Sialylation Levels of Endogenous but Not Therapeutic Intravenous Immunoglobulin G. PLoS ONE 8(12): e81448. doi:10.1371/journal.pone.0081448
Abstract:
Objectives: Although intravenous immunoglobulin (IVIG) is highly effective in Kawasaki disease (KD), mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia) content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I), the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient’s own endogenous IgG. Methods: We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (s)ST6Gal-I levels were measured by ELISA. Results: There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p
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ISSN:
1932-6203
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