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

Chisato Shimizu, Jihoon Kim, Hariklia Eleftherohorinou, Victoria J. Wright, Long T. Hoang, Adriana H. Tremoulet, Alessandra Franco, Martin L. Hibberd, Atsushi Takahashi, Michiaki Kubo, Kaoru Ito, Toshihiro Tanaka, Yoshihiro Onouchi, Lachlan J.M. Coin, Michael Levin, Jane C. Burns, Hiroko Shike

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalHuman Immunology
DOIs
Publication statusPublished - 01-01-2019

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HLA-C Antigens
Mucocutaneous Lymph Node Syndrome
Amino Acid Substitution
Peptides
Alleles
Vasculitis
Nucleotides
HLA-B Antigens
C-Peptide
Disease Susceptibility
Cohort Studies
Pediatrics
T-Lymphocytes
Amino Acids
Incidence
Population
Genes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Shimizu, Chisato ; Kim, Jihoon ; Eleftherohorinou, Hariklia ; Wright, Victoria J. ; Hoang, Long T. ; Tremoulet, Adriana H. ; Franco, Alessandra ; Hibberd, Martin L. ; Takahashi, Atsushi ; Kubo, Michiaki ; Ito, Kaoru ; Tanaka, Toshihiro ; Onouchi, Yoshihiro ; Coin, Lachlan J.M. ; Levin, Michael ; Burns, Jane C. ; Shike, Hiroko. / HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease. In: Human Immunology. 2019.
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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.",
author = "Chisato Shimizu and Jihoon Kim and Hariklia Eleftherohorinou and Wright, {Victoria J.} and Hoang, {Long T.} and Tremoulet, {Adriana H.} and Alessandra Franco and Hibberd, {Martin L.} and Atsushi Takahashi and Michiaki Kubo and Kaoru Ito and Toshihiro Tanaka and Yoshihiro Onouchi and Coin, {Lachlan J.M.} and Michael Levin and Burns, {Jane C.} and Hiroko Shike",
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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 2019, 'HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease', Human Immunology. https://doi.org/10.1016/j.humimm.2019.04.020

HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease. / Shimizu, Chisato; Kim, Jihoon; Eleftherohorinou, Hariklia; Wright, Victoria J.; Hoang, Long T.; Tremoulet, Adriana H.; Franco, Alessandra; Hibberd, Martin L.; Takahashi, Atsushi; Kubo, Michiaki; Ito, Kaoru; Tanaka, Toshihiro; Onouchi, Yoshihiro; Coin, Lachlan J.M.; Levin, Michael; Burns, Jane C.; Shike, Hiroko.

In: Human Immunology, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease

AU - Shimizu, Chisato

AU - Kim, Jihoon

AU - Eleftherohorinou, Hariklia

AU - Wright, Victoria J.

AU - Hoang, Long T.

AU - Tremoulet, Adriana H.

AU - Franco, Alessandra

AU - Hibberd, Martin L.

AU - Takahashi, Atsushi

AU - Kubo, Michiaki

AU - Ito, Kaoru

AU - Tanaka, Toshihiro

AU - Onouchi, Yoshihiro

AU - Coin, Lachlan J.M.

AU - Levin, Michael

AU - Burns, Jane C.

AU - Shike, Hiroko

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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