@article{4d411644f84a4152875fcc360b39dc27,
title = "Prevalence and Impact of De Novo Donor-Specific Antibodies During a Multicenter Immunosuppression Withdrawal Trial in Adult Liver Transplant Recipients",
abstract = "The development of human leukocyte antigen (HLA) donor-specific antibody/antibodies (DSA) is not well described in liver transplant (LT) patients undergoing immunosuppression (IS) withdrawal protocols despite the allograft risk associated with de novo DSA (dnDSA). We analyzed the development of dnDSA in 69 LT patients who received calcineurin inhibitor monotherapy and were enrolled in the ITN030ST study. Of these 69 patients, 40 stable patients were randomized to IS maintenance (n = 9) or IS minimization (n = 31). Nine of the 31 IS minimization patients achieved complete withdrawal and were free of IS. Among patients who achieved stable IS monotherapy 1 year after transplantation, the prevalence of dnDSA was 18.8%. Acute rejections and the biopsy-proven findings disqualifying patients from IS withdrawal attempt were factors associated with dnDSA development (P = 0.011 and P = 0.041, respectively). Among randomized patients, dnDSA prevalence was 51.7% after IS minimization and 66.7% in IS-free patients. dnDSA prevalence in patients on IS maintenance was 44.4%. dnDSA development during IS minimization was a risk factor for acute rejection (P = 0.015). The majority of dnDSA were against HLA-DQ antigens (78.7%). Conclusion. During the first year following transplantation, acute rejections increase the risk of developing dnDSA, so dnDSA positivity should be considered for IS withdrawal eligibility; during IS minimization, dnDSA development was associated with acute rejection, which prevented further IS withdrawal attempts.",
author = "Vadim Jucaud and Abraham Shaked and Michele DesMarais and Peter Sayre and Sandy Feng and Josh Levitsky and Everly, {Matthew J.}",
note = "Funding Information: Received May 21, 2018; accepted September 9, 2018. Additional Supporting Information may be found at onlinelibrary.wiley.com/doi/10.1002/hep.30281/suppinfo. Supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (UM1AI109565). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All HLA antibody screenings were funded by the Terasaki Family Foundation. {\textcopyright} 2018 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.30281 Potential conflict of interest: Dr. Levitsky consults for and owns stock in Transplant Genomics. He is on the speakers{\textquoteright} bureau for and received grants from Novartis. He is on the speakers{\textquoteright} bureau for Gilead. Dr. Feng consults for Juno. She received grants from Novartis and Quark. She owns stock in Abbott, Amgen, Charles River Labs, Eli Lilly, Express Scripts, GlaxoSmithKline, Hospira, Johnson & Johnson, Medco, Merck, Pfizer, and Stryker. Funding Information: All sera samples were screened for anti-HLA antibodies using LABScreen single antigen beads (One Lambda, Canoga Park, CA). All sera were tested at a 1:3 dilution. The mean fluorescence intensity (MFI) cutoff for positivity was 1,000. HLA mismatches were defined based on the high-resolution molecular typing of both donor and recipient for HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ; the DSA were called positive if the exact mismatched HLA antigen (four-digit resolution) was detected. When the exact allele was not present in the single antigen bead panel, the serological specificity was considered as the DSA. The onset MFI was considered to be the MFI of a DSA when it was first detected, and the peak MFI was considered to be the highest DSA MFI over the course of the study. All DSA were confirmed using E3, which is an epitope analysis software developed by the Terasaki Research Institute (Los Angeles, CA). A DSA was considered de novo when that DSA was absent before transplantation. The patients comprising the study population in this analysis were enrolled in the prospective, multicenter, open-label, randomized ITN030ST trial. This trial enrolled adults who underwent a first LT due to liver failure caused by hepatitis C virus (HCV) or nonimmune nonviral causes. Publisher Copyright: {\textcopyright} 2018 by the American Association for the Study of Liver Diseases.",
year = "2019",
month = mar,
doi = "10.1002/hep.30281",
language = "English (US)",
volume = "69",
pages = "1273--1286",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "3",
}