Sensitization in organ transplantation: Assessment of Risk (STAR) 2025 meeting group report

The Sensitization in Transplantation: Assessment of Risk initiative aimed to translate human leukocyte antibody (HLA) laboratory data into clinical practice and identify key knowledge gaps to guide future research. The Sensitization in Transplantation: Assessment of Risk working group has held 3 consensus meetings and published reports that have influenced clinical care. In 2025, the group focused on 5 evolving areas: donor-derived cell-free DNA tests, innate immunity in allograft rejection, immunogenicity and antigenicity, HLA antibody quantification, and non-HLA antibodies. Three years of work culminated in 2 webinars and a February 2025 community meeting, which are summarized in this report. The group outlined considerations for integrating donor-derived cell-free DNA tests into practice, proposed a definition for genetic prediction of natural killer-cell missing self, and discussed monocyte activation via the Signal-regulatory protein alpha - cluster of differentiation 47 (SIRPα-CD47) pathway. They reviewed molecular mismatch approaches, limitations, and immune-recognition complexities. Finally, they provided updates on HLA antibody quantification, non-HLA antibodies, and ongoing studies addressing critical knowledge gaps.