Impact of SIRPα genotype combinations in recipients and donors on alloimmune response in liver transplantation

The signal regulatory protein alpha (SIRPα)-CD47 axis regulates self-tolerance by delivering inhibitory signals to phagocytic cells and influencing immune responses in transplantation. This study examined the impact of SIRPα polymorphisms on CD47 binding capacity and T cell activation and analyzed the role of SIRPα genotypes in acute rejection following allogeneic liver transplantation. Peripheral blood mononuclear cells from healthy volunteers and data from liver transplant recipients were analyzed. Results showed that V2 SIRPα exhibited significantly higher CD47 binding capacity and enhanced costimulatory activity on CD4⁺ T cell proliferation compared V1 under both CD28^- and CD28⁺ conditions, with further augmentation in the CD28⁺ setting. In the liver transplant cohort, SIRPα V2 was associated with higher acute rejection incidences than V1. These findings suggest that SIRPα polymorphisms, particularly V2, enhance T cell activation and modulate alloimmune responses through both innate and adaptive immunity, with potential implications for transplant outcomes. SIRPα genotyping may serve as one component within broader, multiparameter risk models for acute rejection and help inform optimization of immunosuppressive strategies.