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HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease

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3rd Revised Figure for HLA paper Human Immunology final.pdfAccepted version349.9 kBAdobe PDFView/Open
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Title: HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease
Authors: Shimizu, C
Kim, J
Eleftherohorinou, H
Wright, VJ
Hoang, LT
Tremoulet, AH
Franco, A
Hibberd, ML
Takahashi, A
Kubo, M
Ito, K
Tanaka, T
Onouchi, Y
Coin, LJM
Levin, M
Burns, JC
Shike, H
International Kawasaki Disease Genetic Consortium
Item Type: Journal Article
Abstract: Kawasaki disease (KD) is a pediatric vasculitis caused by an unknown trigger in genetically susceptible children. The incidence varies widely across genetically diverse populations. Several associations with HLA Class I alleles have been reported in single cohort studies. Using a genetic approach, from the nine single nucleotide variants (SNVs) associated with KD susceptibility in children of European descent, we identified SNVs near the HLA-C (rs6906846) and HLA-B genes (rs2254556) whose association was replicated in a Japanese descent cohort (rs6906846 p = 0.01, rs2254556 p = 0.005). The risk allele (A at rs6906846) was also associated with HLA-C*07:02 and HLA-C*04:01 in both US multi-ethnic and Japanese cohorts and HLA-C*12:02 only in the Japanese cohort. The risk A-allele was associated with eight non-conservative amino acid substitutions (amino acid positions); Asp or Ser (9), Arg (14), Ala (49), Ala (73), Ala (90), Arg (97), Phe or Ser (99), and Phe or Ser (116) in the HLA-C peptide binding groove that binds peptides for presentation to cytotoxic T cells (CTL). This raises the possibility of increased affinity to a "KD peptide" that contributes to the vasculitis of KD in genetically susceptible children.
Issue Date: Sep-2019
Date of Acceptance: 27-Apr-2019
URI: http://hdl.handle.net/10044/1/70512
DOI: 10.1016/j.humimm.2019.04.020
ISSN: 0198-8859
Publisher: Elsevier
Start Page: 731
End Page: 738
Journal / Book Title: Human Immunology
Volume: 80
Issue: 9
Copyright Statement: © 2019 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Kawasaki disease
HLA-C
Antigen presentation
Amino acid substitution
Cytotoxic T cells
MHC CLASS-I
GENOME-WIDE ASSOCIATION
LOCI
ANTIGENS
MOLECULES
Amino acid substitution
Antigen presentation
Cytotoxic T cells
HLA-C
Kawasaki disease
International Kawasaki Disease Genetic Consortium
Amino acid substitution
Antigen presentation
Cytotoxic T cells
HLA-C
Kawasaki disease
1107 Immunology
Immunology
Publication Status: Published
Conference Place: United States
Online Publication Date: 2019-05-20
Appears in Collections:National Heart and Lung Institute