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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Clinical features and allograft failure rates of pulmonary antibody-mediated rejection categories

Published:September 19, 2022DOI:https://doi.org/10.1016/j.healun.2022.09.012

      Background

      Pulmonary antibody-mediated rejection (AMR) consensus criteria categorize AMR by diagnostic certainty. This study aims to define the clinical features and associated outcomes of these recently defined AMR categories.

      Methods

      Adjudication committees reviewed clinical data of 335 lung transplant recipients to define clinical or subclinical AMR based on the presence of allograft dysfunction, and the primary endpoints, time from transplant to allograft failure, a composite endpoint of chronic lung allograft dysfunction and/or death. Clinical AMR was subcategorized based on diagnostic certainty as definite, probable or possible AMR if 4, 3, or 2 characteristic features were present, respectively. Allograft injury was assessed via plasma donor-derived cell-free DNA (ddcfDNA). Risk of allograft failure and allograft injury was compared for AMR categories using regression models.

      Results

      Over the 38.5 months follow-up, 28.7% of subjects developed clinical AMR (n = 96), 18.5% developed subclinical AMR (n = 62) or 58.3% were no AMR (n = 177). Clinical AMR showed higher risk of allograft failure and ddcfDNA levels compared to subclinical or no AMR. Clinical AMR included definite/probable (n = 21) or possible AMR (n = 75). These subcategories showed similar clinical characteristics, ddcfDNA levels, and risk of allograft failure. However, definite/probable AMR showed greater measures of AMR severity, including degree of allograft dysfunction and risk of death compared to possible AMR.

      Conclusions

      Clinical AMR showed greater risk of allograft failure than subclinical AMR or no AMR. Subcategorization of clinical AMR based on diagnostic certainty correlated with AMR severity and risk of death, but not with the risk of allograft failure.

      Keywords

      Abbreviations:

      AMR (Antibody-Mediated Rejection), CLAD (Chronic lung allograft dysfunction), DSA (donor-specific antibodies), ddcfDNA (donor-derived cell-free DNA), FEV1 (forced expiratory volume in one second), FVC (forced vital capacity), HLA (human leukocyte antigen), MFI (mean fluorescent intensity)
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