Donor-Directed MHC Class I Antibody Is Preferentially Cleared from Sensitized Recipients of Combined Liver/Kidney Transplants

Abstract

For patients with chronic renal and liver diseases, simultaneous liver and kidney transplantation (SLKT) is the best therapeutic option. The role of a pretransplant donor-specific antibody (DSA) in SLKT is unclear. We report the results of a retrospective review from 7/08 to 10/09 of SLKT at our institution. Monitoring of DSA was performed using single antigen bead assay. Between 7/08 and 10/09, there were six SLKT who had preformed DSA and positive XM (four class I and II DSA, one class I DSA only, one class II only). One-year patient and renal graft survival was 83%. Death-censored liver allograft survival was 100%. Acute humoral rejection (AHR) of the kidney occurred in 66% (three with both class I and II DSA and one with only class II DSA) of patients. In those with AHR, class I antibodies were rapidly cleared (p < 0.01) while class II antibodies persisted (p = 0.25). All patients who had humoral rejection of their kidney had preformed anticlass II antibodies. Liver allografts may not be fully protective of the renal allograft, especially with pre-existing MHC class II DSA. Long-term and careful follow-up will be critical to determine the impact of DSA on both allografts. Key words: Antibody-mediated rejection, kidney allograft, liver allograft Abbreviations: SLKT, simultaneous liver kidney transplantation; DSA, donor-specific antibody; AHR, acute humoral rejection; DTT, dithiothreitol; cMCF, delta mean channel fluorescence; MESF, molecules of equivalent soluble fluorescence; MFI, mean fluroescence intensity; AMR, antibody-mediated rejection; HLA, human leukocyte antigen; UNOS, United Network for Organ Sharing; MELD, modified end-stage liver disease; MHC, major histocompatibility complex; IVIG, intravenous immunoglobulin G.

Antibody-mediated rejection in liver transplantation: Current controversies and future directions

“…In our experience, the preexisting DSAs were cleared from the circulation within a week of the transplant in 90% of presensitized recipients. 24 This mopping effect of the liver appears to be more effective against class I HLA antibodies, 52 possibly because of the higher levels of class Why a minority of cross-match-positive patients do not clear preexisting circulating antibodies, whether this can be predicted at the time of transplantation, and whether these antibodies will lead to graft dysfunction in time remain unknown. In contrast, the development of de novo HLA antibodies after liver transplantation may be easier to predict.…”

Combined liver and kidney transplantation in children

“…Thus, the liver offers immunologic protection against AMR of the kidney graft. Recent studies, however, suggest that the liver may not be completely protective [14]. Preformed donor-specific antibodies have been reported to promote AMR, and in a large analysis of over 2,484 CLKT recipients, pre-sensitization had a negative impact on survival of both the patient and the kidney graft [12].…”

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

“…Mendes et al [174] reported on a single center experience of emergency ABO-I LT in 10 patients with severe hepatic failure, immediately leading to death without intervention. Plasmapheresis and IVIg were implemented for immune modulation before and after LT. At a mean follow-up of 19.6 mo post-LT, 5 of these [150] LT n = 1; post-LT, after detection of AMR Plasmapheresis, rituximab Intermittent decrease of Bili, liver enzymes and DSAs'; no survival Dar et al [151] SLKT n = 6; pre-and post-LT desensitization -Survival rate 83.3% Kozlowski et al [142] LT n = 3; post-LT, after detection of AMR Plasmapheresis, rituximab Transient decrease of Bili, yGT and DSAs' in 2 patients; survival rate 33.3% Koch et al [153] SLKT n = 1; post-LT, after liver function deterioration and detection of DSAs'…”

“…studies of desensitization or treatment, decreasing levels of cytotoxic antibodies and improved allograft function (Table 4) were reported [142,[149][150][151][152][153][154][155] . Well-designed studies on this subject are needed.…”