Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss

Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsies and parallel sera from 48 non-sensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsies were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% biopsies. A significantly higher homing capability was expressed by class II sDSAs endowed with high MFI and C3d and/or C1q fixing properties. In patients with available sequential biopsies, we detected gDSAs before the appearance of antibody mediated rejection. In sDSA+ patients, gDSA positivity did not allow to stratify for antibody-mediated graft lesions and graft loss. However, a consistent detection of skewed unique DSA specificities was observed over time within the graft, likely responsible for the damage. Our results indicate that gDSAs could represent an instrumental tool to identify, among sDSAs, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management. This article is protected by copyright. All rights reserved.