In this study, by a parallel analysis on sera and graft biopsies we have analyzed, in a pediatric cohort of unsensitized recipients of a first kidney graft, the role played by graft homing and complement binding capabilities of de novo donor specific HLA antibodies (dnDSA) on graft damage and outcome. Sixty-five graft biopsies and parallel sera obtained from 48 recipients were analyzed. EDTA treated serum samples were tested for the presence of DSA with flow bead technology. In addition, DSA positive sera were tested for complement binding.

Remnant fragments of frozen graft biopsies were processed for antibody acid elution. Serum dn DSA (sdnDSA) were found in 27 patients of this cohort. A total number of 31 graft DSA (gdnDSA) were identified in 25 biopsies. 81 sDSA were detected in 39 parallel positive sera (Class I:38; Class II:43), with a higher median mean fluorescence intensity of sdnDSA Class II (12700) compared to Class I (4400) (p<0.005). gdnDSA were never detected in the absence of sdnDSA, whereas in the presence of sdnDSA, gdnDSA were demonstrated in 64 % of biopsies. A significant higher homing capability was expressed by Class II sdnDSA as compared to Class I DSA ( p<0.005). Graft homing was associated with higher sdnDSA MFI values, both for Class I (p=0.053) and class II DSA (p<0.005). Both C1q and C3d fixing properties resulted strongly correlated with homing capability (p<0.005; p<0.001, respectively). In 4/11 patients exhibiting sequential biopsies, it was possible to detect gdnDSA in the absence of antibody mediated graft insults and subsequently demonstrate a progression to antibody mediated rejection (AMR). Only C3d binding capability of homed sdnDSA was found to correlate with a significant lower graft survival (p<0.05). In conclusion, gdnDSAcan be found also in early phases of antibody mediated graft damage, and, accordingly, the homing process could be seen as the preliminary step of graft tissue insult.

CITATION INFORMATION: Nocera A, Cioni M, Tagliamacco A, Innocente A, Fontana I, Magnasco A, Nocco A, Sementa A, Garibotto G, Ghiggeri G, Cardillo M, Comoli P, Ginevri F. Kidney Graft Homing of De Novo Donor Specific HLA Antibodies Is an Early Step within the Antibody-Mediated Graft Damage Process. Am J Transplant. 2016;16 (suppl 3).

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