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

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3 Citations (Scopus)

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
Pages (from-to)731-738
Number of pages8
JournalHuman Immunology
Volume80
Issue number9
DOIs
Publication statusPublished - 09-2019

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Shimizu, C., Kim, J., Eleftherohorinou, H., Wright, V. J., Hoang, L. T., Tremoulet, A. H., Franco, A., Hibberd, M. L., Takahashi, A., Kubo, M., Ito, K., Tanaka, T., Onouchi, Y., Coin, L. J. M., Levin, M., Burns, J. C., & Shike, H. (2019). HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease. Human Immunology, 80(9), 731-738. https://doi.org/10.1016/j.humimm.2019.04.020