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Evolutionary divergence and expression of differential HLA alleles between donor and recipient influence acute GVHD onset after allogenetic HSCT

Chen, Y.; Zhan, W.; Zhang, Y.; Gao, H.; Han, Y.; Qiao, J.; Li, Z.; Liu, Y.; Li, Y.; Yang, S.; Guo, Y.; Wang, X.; Li, F.; Wang, X.; He, P.; Gao, P.

2025-12-12 hematology
10.64898/2025.12.10.25342012 medRxiv
Show abstract

Acute graft-versus-host disease (aGVHD) remains a major complication after hematopoietic stem cell transplantation (HSCT), especially given haploidentical HSCT is now Chinas primary method, yet this context lacks reliable predictors. aGVHD initiation, involving donor T cell activation by recipient conventional dendritic cells (cDCs), depends on donor-recipient HLA disparity and its expression. We therefore developed the donor and recipient-specific HLA evolutionary divergence (DRs_HED) algorithm to quantify relevant HLA differences, then integrated HLA expression in cDC to evaluate the combined predictive value. While DRs_HED correlated with aGVHD occurrence, links to organ severity varied: consistent for skin but not gastrointestinal aGVHD. Only cDCs expression of HLA-DRB1 correlated with presentation of associated minor histocompatibility antigens (miHAs). Integrating expression with DRs_HED improved prediction, raising the models AUC by about [~]10% to 0.607 {+/-} 0.012 versus DRs_HED alone. Our findings show precise quantification of HLA disparity and expression improves aGVHD risk prediction, aiding future multi-factorial models.

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