Characterizing pre-transplant and post-transplant kidney rejection risk by B cell immune repertoire sequencing

Studying immune repertoire in the context of organ transplant provides important information on how adaptive immunity may contribute and modulate graft rejection. Here we characterize the peripheral blood immune repertoire of individuals before and after kidney transplant using B cell receptor sequencing in a longitudinal clinical study. Individuals who develop rejection after transplantation have a more diverse immune repertoire before transplant, suggesting a predisposition for post-transplant rejection risk. Additionally, over 2 years of follow-up, patients who develop rejection demonstrate a specific set of expanded clones that persist after the rejection. While there is an overall reduction of peripheral B cell diversity, likely due to increased general immunosuppression exposure in this cohort, the detection of specific IGHV gene usage across all rejecting patients supports that a common pool of immunogenic antigens may drive post-transplant rejection. Our findings may have clinical implications for the prediction and clinical management of kidney transplant rejection.