Kidney transplantation is the treatment of choice for end-stage kidney disease, yet alloimmune responses remain the leading cause of graft dysfunction and loss. Despite advances in immunosuppression, both acute and chronic forms of rejection continue to limit long-term outcomes.

This Research Topic seeks to assemble mechanistic, translational, and clinical studies that elucidate how alloantibodies arise, how they injure the allograft, and how these insights can be leveraged into precise diagnostics and targeted therapies.

We particularly welcome submissions focusing on, but not limited to:

• Deep mechanistic view of antibody-mediated rejection (AMR) across its continuum (pre-sensitization, desensitization, de novo sensitization, chronic active AMR). Areas of emphasis include: the generation and maintenance of B-cell and long-lived plasma cell responses; control of humoral immunity; molecular rules of epitope/eplet mismatch and their relationship to donor-specific antibody (DSA) breadth, affinity, and maturation; non-HLA antibodies and their functional impact; and IgG Fc biology, including FcγR engagement, complement activation, and Fc glycosylation as a modulator of pathogenic effector functions.

• Translational insights into monitoring, predicting, and managing alloimmune responses: development and validation of biomarkers (donor-derived cfDNA, endothelial injury and complement signatures, urinary chemokines, molecular microscope profiles), multiplex tissue phenotyping, and integrative risk models that predict AMR occurrence, trajectory, and treatment response. We welcome studies on monitoring minimal residual alloimmunity, kinetics of DSA clearance, and surrogate endpoints suitable for early-phase trials.

• Novel immunomodulatory approaches, including biologics, small molecules, and cellular therapies. Therapeutic topics of interest include biologics and small molecules targeting B-cells/plasma cells, cytokine and costimulation pathways, complement inhibitors, cellular therapies, and desensitization strategies linked to mechanistic biomarkers.

• Rigorous evaluations of protocol standardization, optimization of therapeutic drug monitoring, and adaptive trial designs that couple mechanistic readouts to clinical endpoints.

• Clinical perspectives spanning disease recurrence in the allograft, pediatric transplantation, health-disparity and ethical considerations in access to desensitization/AMR therapies, and long-term graft survival.

By anchoring fundamental immunobiology to actionable diagnostics and interventions this collection aims to catalyze precision, mechanism-informed strategies that improve durable graft survival and patient outcomes.

Are you interested in contributing a manuscript to this Research Topic?

Alloimmunity in Kidney Transplantation: From Mechanisms to Clinical Translation