The Impact of Preformed Donor-specific Antibodies in Living Donor Liver Transplantation According to Graft Volume

Overview

Journal Immun Inflamm Dis

Specialties Allergy & Immunology
Infectious Diseases

Date 2022 Jan 22

PMID 35064772

Authors

Ryoichi Goto

Makoto Ito

Norio Kawamura

Masaaki Watanabe

Yoshikazu Ganchiku

Toshiya Kamiyama

Tsuyoshi Shimamura

Akinobu Taketomi

Affiliations

Soon will be listed here.

Abstract

Introduction: The roles of preformed anti-HLA donor-specific antibodies (DSAs) in liver transplantation remain controversial. We evaluated the impact of preformed DSAs in living donor liver transplantation.

Methods: Adults who underwent living donor liver transplantation (n = 175) in our institute were included in this study. Lymphocyte cytotoxicity test (LCT), flow cytometric crossmatch (FCXM), and single-antigen bead assays were performed.

Results: Among adult living donor liver transplantation recipients, 27 (16.5%) and 14 (8.5%) had pretransplant FCXM-positive findings and LCT-positive findings, respectively. FCXM-positive patients displayed a significantly worse 5-year graft survival rate (77.3%; vs. DSA-negative, 91.6%). Six of 14 LCT-positive patients exhibited graft loss shortly after transplantation (5-year survival rate: 57.1%). All LCT-positive patients with graft loss underwent left lobe living donor liver transplantation. Significantly lower ratio of graft volume relative to standard liver volume (32.9 ± 5.7%) and smaller graft size (365.3 ± 57.9 g) were observed in patients with graft loss (p < .03, vs. surviving grafts). Significantly higher DSA-mean fluorescence intensity (MFI) values were present in patients with graft loss (p = .0012, vs. surviving grafts).

Conclusions: Patients with preformed DSAs exhibited worse graft outcomes in living donor liver transplantation. Higher DSA-MFI values and smaller graft size were associated with worse outcomes in LCT-positive patients. High-risk patients with preformed DSAs should be considered for appropriate graft selection and application of a desensitization protocol.

Citing Articles

The impact of donor-specific antibodies' presence on the outcome post-allogeneic hematopoietic stem cell transplantation: a survey from a single center.

Sica S, Metafuni E, Frioni F, Limongiello M, Galli E, Sora F Front Oncol. 2024; 14:1387181.

PMID: 39234400 PMC: 11371551. DOI: 10.3389/fonc.2024.1387181.

Post-transplant donor-specific anti-HLA antibodies with a higher mean fluorescence intensity are associated with graft fibrosis in pediatric living donor liver transplantation.

Goto R, Fukasaku Y, Ganchiku Y, Kawamura N, Watanabe M, Ota T Front Pediatr. 2023; 11:1172516.

PMID: 37181419 PMC: 10168538. DOI: 10.3389/fped.2023.1172516.

Importance of human leukocyte antigen antibodies and leukocyte antigen/killer-cell immunoglobulin-like receptor genes in liver transplantation.

Muro M, Legaz I World J Gastroenterol. 2023; 29(5):766-772.

PMID: 36816626 PMC: 9932425. DOI: 10.3748/wjg.v29.i5.766.

The impact of preformed donor-specific antibodies in living donor liver transplantation according to graft volume.

Goto R, Ito M, Kawamura N, Watanabe M, Ganchiku Y, Kamiyama T Immun Inflamm Dis. 2022; 10(3):e586.

PMID: 35064772 PMC: 8926496. DOI: 10.1002/iid3.586.

References

Scornik J, Soldevilla-Pico C, Van der Werf W, Hemming A, Reed A, Langham Jr M . Susceptibility of liver allografts to high or low concentrations of preformed antibodies as measured by flow cytometry. Am J Transplant. 2002; 1(2):152-6. DOI: 10.1034/j.1600-6143.2001.10209.x. View

OLeary J, Kaneku H, Jennings L, Banuelos N, Susskind B, Terasaki P . Preformed class II donor-specific antibodies are associated with an increased risk of early rejection after liver transplantation. Liver Transpl. 2013; 19(9):973-80. DOI: 10.1002/lt.23687. View

Del Bello A, Neau-Cransac M, Lavayssiere L, Dubois V, Congy-Jolivet N, Visentin J . Outcome of Liver Transplant Patients With Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibodies. Liver Transpl. 2019; 26(2):256-267. DOI: 10.1002/lt.25663. View

Ashihara E, Tsuji H, Sakashita H, Haga H, Yurugi K, Kimura S . Antidonor antibody in patients receiving ABO-identical and HLA-mismatched living donor liver transplants: effect on survival. Transplantation. 2007; 83(4):506-9. DOI: 10.1097/01.tp.0000251361.12249.a1. View

Nakamura K, Murase N, Becich M, Furuya T, Todo S, Fung J . Liver allograft rejection in sensitized recipients. Observations in a clinically relevant small animal model. Am J Pathol. 1993; 142(5):1383-91. PMC: 1886908. View

Reichman T, Katchman H, Tanaka T, Greig P, McGilvray I, Cattral M . Living donor versus deceased donor liver transplantation: a surgeon-matched comparison of recipient morbidity and outcomes. Transpl Int. 2013; 26(8):780-7. DOI: 10.1111/tri.12127. View

Koch M, Marget M, Sterneck M, Fischer L, Thude H, Nashan B . Limited impact of pre-existing donor specific HLA-antibodies (DSA) on long term allograft survival after first adult liver transplantation. Hum Immunol. 2018; 79(7):545-549. DOI: 10.1016/j.humimm.2018.04.009. View

Demetris A, Bellamy C, Gandhi C, Prost S, Nakanuma Y, Stolz D . Functional Immune Anatomy of the Liver-As an Allograft. Am J Transplant. 2016; 16(6):1653-80. DOI: 10.1111/ajt.13749. View

Tambur A, Wiebe C . HLA Diagnostics: Evaluating DSA Strength by Titration. Transplantation. 2017; 102(1S Suppl 1):S23-S30. DOI: 10.1097/TP.0000000000001817. View

10.

Sugawara Y, Tamura S, Kaneko J, Togashi J, Makuuchi M, Kokudo N . Positive lymphocytotoxic crossmatch does not adversely affect survival in living donor liver transplantation. Dig Surg. 2010; 26(6):482-6. DOI: 10.1159/000253873. View

11.

Gordon R, Fung J, Markus B, Fox I, Iwatsuki S, Esquivel C . The antibody crossmatch in liver transplantation. Surgery. 1986; 100(4):705-15. PMC: 3095820. View

12.

Levitsky J, Kaneku H, Jie C, Walsh R, Abecassis M, Tambur A . Donor-Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients. Am J Transplant. 2016; 16(8):2437-44. DOI: 10.1111/ajt.13757. View

13.

Jeannet M, Pinn V, FLAX M, Winn H, Russell P . Humoral antibodies in renal allotransplantation in man. N Engl J Med. 1970; 282(3):111-7. DOI: 10.1056/NEJM197001152820301. View

14.

Lunz J, Ruppert K, Cajaiba M, Isse K, Bentlejewski C, Minervini M . Re-examination of the lymphocytotoxic crossmatch in liver transplantation: can C4d stains help in monitoring?. Am J Transplant. 2011; 12(1):171-82. DOI: 10.1111/j.1600-6143.2011.03786.x. View

15.

Ide K, Tanaka Y, Sasaki Y, Tahara H, Ohira M, Ishiyama K . A Phased Desensitization Protocol With Rituximab and Bortezomib for Highly Sensitized Kidney Transplant Candidates. Transplant Direct. 2016; 1(5):e17. PMC: 4946466. DOI: 10.1097/TXD.0000000000000526. View

16.

Legaz I, Boix F, Lopez M, Alfaro R, Galian J, Llorente S . Influence of Preformed Antibodies in Liver Transplantation. J Clin Med. 2020; 9(3). PMC: 7141359. DOI: 10.3390/jcm9030708. View

17.

Tamura K, Tohyama T, Watanabe J, Nakamura T, Ueno Y, Inoue H . Preformed donor-specific antibodies are associated with 90-day mortality in living-donor liver transplantation. Hepatol Res. 2019; 49(8):929-941. DOI: 10.1111/hepr.13352. View

18.

McCaughan J, Robertson V, Falconer S, Cryer C, Turner D, Oniscu G . Preformed donor-specific HLA antibodies are associated with increased risk of early mortality after liver transplantation. Clin Transplant. 2016; 30(12):1538-1544. DOI: 10.1111/ctr.12851. View

19.

Suah A, Tran D, Khiew S, Andrade M, Pollard J, Jain D . Pregnancy-induced humoral sensitization overrides T cell tolerance to fetus-matched allografts in mice. J Clin Invest. 2021; 131(1). PMC: 7773355. DOI: 10.1172/JCI140715. View

20.

OLeary J, Demetris A, Friedman L, Gebel H, Halloran P, Kirk A . The role of donor-specific HLA alloantibodies in liver transplantation. Am J Transplant. 2014; 14(4):779-87. PMC: 4412601. DOI: 10.1111/ajt.12667. View