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Title: Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G
Authors: Ogata S.
Shimizu C.
Franco A.
Touma R.
Kanegaye J.T.
Choudhury B.P.
Naidu N.N.
Kanda Y.
Hoang L.T.
Hibberd M.L. 
Tremoulet A.H.
Varki A.
Burns J.C.
Keywords: acetylsalicylic acid
beta galactoside a2 6 sialyltransferase I
immunoglobulin G
unclassified drug
cell lysate
controlled study
disease association
enzyme blood level
enzyme linked immunosorbent assay
gene expression
human cell
major clinical study
mucocutaneous lymph node syndrome
protein blood level
quantitative analysis
reverse transcription polymerase chain reaction
treatment failure
treatment response
Case-Control Studies
Cell Line
Child, Preschool
Enzyme-Linked Immunosorbent Assay
Immunoglobulins, Intravenous
Mucocutaneous Lymph Node Syndrome
N-Acetylneuraminic Acid
Oligonucleotide Array Sequence Analysis
RNA, Messenger
Treatment Outcome
Issue Date: 2013
Citation: Ogata S., Shimizu C., Franco A., Touma R., Kanegaye J.T., Choudhury B.P., Naidu N.N., Kanda Y., Hoang L.T., Hibberd M.L., Tremoulet A.H., Varki A., Burns J.C. (2013). Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G. PLoS ONE 8 (12) : e81448. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
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 ⍺2-6-linked sialic acid (?2-6Sia) content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of ⍺-galactoside:⍺2-6 sialyltransferase-I (ST6Gal-I), the enzyme that catalyzes addition of ⍺2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of ⍺2-6Sia on infused IVIG or on the patient's own endogenous IgG. Methods: We quantified levels of ⍺2-6Sia 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, ⍺2-6Sia 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 <0.001, respectively). Conclusions: Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals. Copyright: © 2013 Ogata et al.
Source Title: PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0081448
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications

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