Carrie A. Schinstock, Howard Gebel, Idoia Gimferrer, Marlena Habal, Sebastiaan Heidt, Michelle J. Hickey, Annette. Jackson, Vasilis Kosmoliaptsis, Roslyn B. Mannon, Maria Meneghini, M. Mengel, Anna Morris, Maarten Naesens, Elaine Reed, Aleksandar Senev, O. Thaunat, Nicole M. Valenzuela, Chris Wiebe, Anat R. Tambur
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.