Differences in Pathologic Features and Graft Outcomes in Antibody-mediated Rejection of Renal Allografts Due to Persistent/recurrent Versus De Novo Donor-specific Antibodies

Antibody-mediated rejection (ABMR) of renal allografts occurs in two forms. Type 1 ABMR results from persistence and/or a rebound of preexisting donor-specific antibodies in sensitized patients and usually occurs early post-transplantation. Type 2 ABMR is associated with de novo donor-specific antibodies and usually occurs over one year post-transplantation. It is generally accepted that types 1 and 2 also differ with regard to certain pathologic features including the frequencies of C4d positivity and concurrent cell-mediated rejection. However, direct comparison of pathologic, serologic, and clinical features of types 1 and 2 ABMR is lacking. Here we compared these features in 80 cases of ABMR (37 type 1, 43 type 2) diagnosed at our center. Compared with type 1, type 2 ABMR occurred later post-transplantation, was more often associated with donor-specific antibodies against Class II HLA, and was associated with more interstitial fibrosis/tubular atrophy and more frequent cell-mediated rejection, although these did not differ with respect to C4d positivity. By univariate analysis, graft survival was lower with type 2 than type 1 ABMR with borderline significance. Still, among these 80 patients, all but one treated for ABMR following diagnosis, the only two independent predictors of graft failure were at least moderate interstitial fibrosis/tubular atrophy and failure of the donor-specific antibody relative intensity scale score, a measure of the combined strength of all donor-specific antibodies present, to decrease in response to therapy.