Intragraft donor-specific antibodies reflect histologic heterogeneity in kidney allografts with concurrent serum DSA

Circulating donor-specific antibodies (sDSA) are clinically important markers of alloimmune risk, but their presence or strength does not always correspond to concurrent antibody-mediated rejection (ABMR) in kidney transplantation. We investigated whether intragraft donor-specific antibodies (gDSA) detected in kidney biopsy eluates are associated with histologic findings in recipients with concurrent sDSA positivity.

All available frozen kidney biopsies in recipients with concurrent weak to moderate sDSA at Seoul National University Hospital between January 2020 and June 2024 were included. Sixty biopsy eluates from 60 patients were tested using a Luminex single antigen bead assay and analyzed according to biopsy findings.

The prevalence of gDSA differed significantly across histologic diagnoses (overall P = 3.3 × 10^-4), with higher positivity in C4d-only lesions (100.0%), aABMR (90.9%) and aABMR+TCMR (83.3%), whereas lower frequencies were observed in caABMR (44.4%), no rejection (22.7%), and aTCMR (14.3%). The gDSA positive rate in aABMR was significantly higher than that in the no-rejection group (corrected P = 0.003; OR 34, 95% CI 3.5-334). The MFI sum of gDSA was significantly higher in aABMR, aABMR+TCMR, and C4d-only lesions (corrected P = 0.009, 0.035, and 0.007, respectively). In contrast, the sum of sDSA MFI did not differ significantly across the histologic groups.

In kidney transplant recipients with concurrent sDSA, the presence and intensity of gDSA varied according to biopsy-proven histologic findings, most prominently in aABMR and related lesions. These findings suggest that gDSA may provide additional tissue-level immunologic context for understanding histologic heterogeneity among kidney transplant recipients with circulating sDSA.