2025-06-10 京都大学
<関連情報>
- https://www.kyoto-u.ac.jp/ja/research-news/2025-06-10-2
- https://www.kyoto-u.ac.jp/sites/default/files/2025-06/web_2506_Ito-408393ee8d6633fa4f9fcace9cebdd93.pdf
- https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00226-5
固形臓器移植におけるドナー特異的抗体開発におけるHLA分子ミスマッチの臓器横断的階層性 Cross-organ hierarchy of HLA molecular mismatches in donor-specific antibody development in solid organ transplantations
Masaaki Hirata ∙ Kazuto Tsukita ∙ Takero Shindo ∙ … ∙ Takashi Kobayashi ∙ Hiroshi Date ∙ Etsuro Hatano
Cell Reports Medicine Published:May 30, 2025
DOI:https://doi.org/10.1016/j.xcrm.2025.102153
Highlights
•Eplet-wide analyses reveal a hierarchy among HLA eplet mismatches driving DSA risk
•This hierarchy is conserved across various solid organ transplantations
•Eplet risk score (ERS) captures this hierarchy, accurately predicting DSA development
•ERS correlates with CD4+ T cell proliferation in mixed lymphocyte reaction
Summary
Donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) play a crucial role in antibody-mediated rejection, a major barrier to successful organ transplantation. Donor-recipient HLA molecular incompatibility critically influences DSA susceptibility, commonly assessed by analyzing mismatches in the HLA eplet repertoire. This study, including six distinct liver, lung, and kidney transplant cohorts from two centers (978 donor-recipient pairs), explores associations between individual eplet mismatches and DSA development. Certain mismatched eplets are strongly linked to DSA development, while others show weaker associations, a trend consistent across different organ types. Machine learning leverages these hierarchical associations to develop an eplet risk score (ERS), outperforming traditional eplet mismatch assessments. Furthermore, T cell proliferation in mixed lymphocyte reaction in vitro correlates with the ERS, attenuated by antibody-mediated inhibition of a mismatched DSA-associated eplet. These results establish the differential immunological impacts of mismatched HLA eplets as integral in clinical practice and therapeutic innovation.
