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Utility of Screening-Bead Assay in Testing for Formation of Donor-Specific Anti-HLA Antibodies and Antibody-Mediated Rejection in Renal Allografts Post-Transplant.

  • Author / Creator
    Agrawal, Amogh
  • Background: Present-day immunosuppressive therapy in renal allograft recipients targets cell-mediated immunity and has significantly improved outcomes over the years. However, allograft failure rates still approach 50% towards 10 years post-transplantation. Antibody-mediated rejection (ABMR) is being increasingly recognized as a major cause of poor long-term graft survival. Though it can aid in risk stratification and optimizing immune-suppression, post-transplant monitoring of anti-HLA donor specific-antibodies (DSAs) is controversial as it is costly and there is little data that early detection impacts outcomes. Moreover, the best way to test for DSAs is not well-established. Some centres use an initial screening-bead assay, claiming it is cost-effective. Others forego the screening-bead assay, as they believe it is not sensitive enough to warrant its use. This study aims to establish the screening bead assay’s utility by measuring its sensitivity, specificity, and negative and positive predictive values and likelihood ratios.

    Methods: The screening-bead assay’s clinical utility was retrospectively determined by comparing it to single-antigen bead assays as a surrogate for detecting anti-HLA-antibodies and renal biopsies as a surrogate for detecting antibody-mediated rejection. Further, screening-bead assays were correlated to changes in serum creatinine and eGFR over time. These data had been collected from renal allograft recipients at the University of Alberta Hospital between 2013-2017.

    Results: Overall, positive results had less clinical utility than did negative results. Sensitivity for anti-HLA antibodies was 90.6%, 95% CI [87.5%, 93.8%], negative predictive value was 87.1% when re-calculated for literature-reported prevalence of anti-HLA antibodies and 94.2% to 96.3% when re-calculated for literature-reported prevalence of de novo donor-specific anti-HLA antibodies. Negative likelihood ratio for anti-HLA antibodies was 0.345. Sensitivity for antibody-mediated rejection was 91.3%, 95% CI [79.8%, 100%], negative predictive value was 89.1% to 92.8% when re-calculated for literature-reported prevalence of antibody-mediated rejection and negative likelihood ratio was 0.70. When recalculated for de novo donor-specific anti-HLA antibodies that were identified by screens and single-antigen bead assays, these values improved to 94.7%, 95% CI [84.7%, 100%], 97.4% to 98.3% and 0.15 respectively. Further, positive screens correlated with a more aggressive decline in renal function, though degree of positivity of the screen was not prognostic.

    Conclusions: The screening-bead assay’s negative predictive value and sensitivity were high enough to warrant its use as a screening measure for formation of de novo anti-HLA donor-specific antibodies in previously unsensitized renal transplant recipients and those with low clinical suspicion of antibody-mediated rejection. Its use is less compulsory in those who are already sensitized and those who have high pre-clinical suspicion of antibody-mediated rejection.

  • Subjects / Keywords
  • Graduation date
    Fall 2020
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/r3-n4g9-tp03
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.