Chronic-active antibody-mediated rejection with or without donor-specific antibodies has similar histomorphology and clinical outcome - a retrospective study

Abstract

Chronic-active antibody-mediated rejection (c-aABMR) is defined as histological evidence of chronic endothelial injury (cg), also known as transplant glomerulopathy, and either microvascular inflammation (MVI) or positivity for C4d. Importantly, the presence of donor-specific antibodies (DSA) is currently still mandatory for the diagnosis of c-aABMR. This retrospective study of 41 c-aABMR patients investigates whether cases suspicious for c-aABMR (DSA negative, n = 24) differ from cases of c-aABMR (DSA positive, n = 17) with respect to renal histology, allograft function and long-term graft survival. All included patients had progressive loss of allograft function and were diagnosed by for cause biopsy and scored according to the Banff '15 criteria. In all DSApos cases, DSA were de novo and the majority was directed against HLA-II being mostly anti-HLA-DQ antibodies. There were no statistically significant differences in clinical characteristics, decline in allograft function and renal allograft survival in cases with or without DSAs. All cases showed chronic histomorphological damage and inflammation, irrespective of the presence of DSA. Renal histology and clinical outcome of patients suspicious for c-aABMR (DSAneg) do not significantly differ from patients with a diagnosis of c-aABMR (DSApos). We believe that our study adds to the ongoing debate regarding the need for DSAs to be present for the diagnosis of c-aABMR.

The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell– and antibody-mediated rejection

“…DSA+ patients were more frequently retransplant recipients and had C4d+ biopsies. By contrast, studies of patients biopsied much later with more severe MVI and frequent transplant glomerulopathy (TG) showed no difference in graft survival in the presence or absence of anti‐HLA DSAs, which in these studies were de novo DSAs 22,23 . Thus, at this point, we are unable to draw significant conclusions regarding the significance of biopsies showing (g + ptc >2) in the absence of anti‐HLA DSAs, other than to comment that the biological behavior of such changes may well differ depending on whether these are seen relatively early posttransplant at a time when many DSAs represent persistent or recurrent/memory DSAs vs those seen later when most DSAs detected are de novo DSAs.…”

Increased CD16 expression on NK cells is indicative of antibody-dependent cell-mediated cytotoxicity in chronic-active antibody-mediated rejection

“…Pre-transplant donor specific antibodies against HLA (DSA) and de novo DSA, which develop after transplantation, play an important role in the development of c-aABMR [8]. However, in a substantial number of cases DSA cannot be detected in the serum at time of diagnosis [9][10][11][12].…”

Banff lesions and renal allograft survival in chronic-active antibody mediated rejection

“…None of the Banff lesions related with the degree of proteinuria at time of biopsy. As has been previously published, no relation between the presence of DSA in the serum, Banff scores and graft survival could be found [19].…”