Abstract
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.
Highlights
Studying immune repertoire in the context of organ transplant provides important information on how adaptive immunity may contribute and modulate graft rejection
Three clinical phenotype groups, defined by blinded central pathology reads of serial allograft biopsies scored by Banff criteria[23,24] and the chronic allograft damage index (CADI) score were considered in this study: Nonprogressors (NP; n = 10) had low non-incremental CADI score without acute rejection, progressors with no rejection (PNR; n = 10) had incremental CADI score over 2 years without rejection, and progressors with rejection (PR; n = 7) had incremental high CADI scores over 2 years with rejection episodes
We found that NP and PR behaved differently across time after transplant showing an increase in diversity in NP and a decrease in diversity in PR, while for PNR the diversity remained invariable across time
Summary
Studying immune repertoire in the context of organ transplant provides important information on how adaptive immunity may contribute and modulate graft 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. The role of T cells in organ transplant rejection has been demonstrated[7], but there is increasing appreciation of the additional role of B cells and antibodies in triggering this process[8]. In this regard, B-cell receptor sequencing (BCRSeq) is a promising high-throughput technique[9] that allows the sequencing of millions of Immunoglobulin (Ig) regions in parallel to study the immune response. Antigen binding occurs in the variable domain, which is generated by recombination of a set of variable (V), diversity (D)
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