Comparing Antibody-Mediated Rejection with or without Detectable DSA: Similar Pathology and Similar Poor Prognosis
1Dpt. of Nephrology, Hannover Medical School, Hannover, Germany, 2Dpt. of Laboratory Medicine and Pathology and Alberta Transplant Applied Genomics Centre, University of Alberta, Edmonton, AB, Canada, 3Dpt. of Nephrology and Alberta Transplant Applied Genomics Centre, University of Alberta, Edmonton, AB, Canada
Meeting: 2019 American Transplant Congress
Abstract number: 321
Keywords: Biopsy, Gene expression, HLA antibodies, Rejection
Session Information
Date: Monday, June 3, 2019
Session Name: Concurrent Session: Kidney Chronic Antibody Mediated Rejection
Session Time: 4:30pm-6:00pm
Presentation Time: 5:18pm-5:30pm
Location: Ballroom B
*Purpose: Banff guidelines require the detection of donor-specific antibodies (DSA) in addition to microvascular inflammation (MVI) for a diagnosis of antibody-mediated rejection (ABMR), but MVI is also common with no DSA and its significance is unknown.
*Methods: We assessed molecular, clinical, and histologic changes in histologically-defined ABMR in kidney transplant indication biopsies assessed by the Molecular Microscope system (MMDx) (n = 1208). We identified biopsies with MVI meeting Banff 2017 criteria for active ABMR (g > 0 and/or ptc > 0 when C4d>0; or g + ptc ≥ 2 when C4d = 0 or unknown) and compared the molecular ABMR features in biopsies with MVI and DSA to those with MVI but no detectable DSA. Biopsies with TCMR or borderline TCMR, incomplete Banff scoring or unknown HLA antibody status were excluded.
*Results: Of n = 180 biopsies with MVI criteria for ABMR, n = 56 (31%) had no DSA. Of these, n = 21 were PRA+, n = 22 were PRA- (n = 13 with unknown PRA status). The molecular changes of ABMR were highest in the DSA+ patients, lower in PRA+/DSA- and lowest in PRA- patients; markers of tissue injury were similarly abnormal in all groups (Fig1). 79% of DSA+ patients with histologic ABMR had no molecular ABMR (defined by archetype analysis). The rate of molecular ABMR was lower in DSA- patients with histologic ABMR (61%), and lowest in PRA- patients (36%). The frequency of early molecular ABMR was similar in DSA+ vs. DSA- patients with histologic ABMR-like MVI, but DSA- patients had less fully developed ABMR and more late ABMR than DSA+ patients. Graft survival at three years post biopsy was similar in DSA+ and DSA- patients. However, DSA+ patients have higher GFR at biopsy (50.9 ± 24.0) than DSA- patients (39.7 ± 18.8), suggesting that they progress more quickly than DSA- patients with histologic ABMR.
*Conclusions: Thus DSA+ and DSA- patients with ABMR-like MVI have similar histologic features and graft loss and share many molecular features, but have some molecular differences: DSA- patients have less molecular ABMR activity and more late ABMR features, suggesting that DSA loss is a stage in ABMR progression in some patients. However, the nature of the agents causing the ABMR-like changes and progression in DSA- patients needs to be defined.
To cite this abstract in AMA style:
Einecke G, Reeve J, Halloran PF. Comparing Antibody-Mediated Rejection with or without Detectable DSA: Similar Pathology and Similar Poor Prognosis [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/comparing-antibody-mediated-rejection-with-or-without-detectable-dsa-similar-pathology-and-similar-poor-prognosis/. Accessed February 26, 2021.« Back to 2019 American Transplant Congress