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Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus induced by immune-checkpoint inhibitors

Frontiers in Immunology, ISSN: 1664-3224, Vol: 14, Page: 1165004
2023
  • 6
    Citations
  • 0
    Usage
  • 6
    Captures
  • 1
    Mentions
  • 6
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    6
  • Captures
    6
  • Mentions
    1
    • News Mentions
      1
      • 1
  • Social Media
    6
    • Shares, Likes & Comments
      6
      • Facebook
        6

Most Recent News

Data on Type 1 Diabetes Discussed by Researchers at Japanese Red Cross Wakayama Medical Center (Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus ...)

2023 APR 24 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Daily -- Research findings on type 1 diabetes are discussed

Article Description

Introduction: Immune-checkpoint inhibitors are effective in various advanced cancers. Type 1 diabetes mellitus induced by them (ICI-T1DM) is a serious complication requiring prompt insulin treatment, but the immunological mechanism behind it is unclear. Methods: We examined amino acid polymorphisms in human histocompatibility leukocyte antigen (HLA) molecules and investigated proinsulin epitope binding affinities to HLA molecules. Results and Discussion: Twelve patients with ICI-T1DM and 35 patients in a control group without ICI-T1DM were enrolled in the study. Allele and haplotype frequencies of HLA-DRB1*04:05, DQB1*04:01, and most importantly DPB1*05:01 were significantly increased in patients with ICI-T1DM. In addition, novel amino acid polymorphisms in HLA-DR (4 polymorphisms), in DQ (12 polymorphisms), and in DP molecules (9 polymorphisms) were identified. These amino acid polymorphisms might be associated with the development of ICI-T1DM. Moreover, novel human proinsulin epitope clusters in insulin A and B chains were discovered in silico and in vitro peptide binding assays to HLA-DP5. In conclusion, significant amino acid polymorphisms in HLA-class II molecules, and conformational alterations in the peptide-binding groove of the HLA-DP molecules were considered likely to influence the immunogenicity of proinsulin epitopes in ICI-T1DM. These amino acid polymorphisms and HLA-DP5 may be predictive genetic factors for ICI-T1DM.

Bibliographic Details

Inaba, Hidefumi; Morita, Shuhei; Kosugi, Daisuke; Asai, Yuki; Kaido, Yosuke; Ito, Saya; Hirobata, Tomonao; Inoue, Gen; Yamamoto, Yuki; Jinnin, Masatoshi; Kimura, Hiroaki; Ota, Masao; Okudaira, Yuko; Nakatani, Hiroyasu; Kobayashi, Tomoko; Iwama, Shintaro; Arima, Hiroshi; Matsuoka, Takaaki

Frontiers Media SA

Medicine; Immunology and Microbiology

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