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
- 6Citations
- 6Captures
- 1Mentions
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Metrics Details
- Citations6
- Citation Indexes6
- Captures6
- Readers6
- Mentions1
- News Mentions1
- 1
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
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85153509517&origin=inward; http://dx.doi.org/10.3389/fimmu.2023.1165004; http://www.ncbi.nlm.nih.gov/pubmed/37114039; https://www.frontiersin.org/articles/10.3389/fimmu.2023.1165004/full; https://dx.doi.org/10.3389/fimmu.2023.1165004; https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1165004/full
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