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Published on: July 10, 2012
Clinical features and allograft failure rates of pulmonary antibody-mediated rejection categories
Ananth V Charya1, Ileana L Ponor2, Adam Cochrane3
1Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Division of Pulmonary and Critical Care, University of Maryland Medical Center, Baltimore, Maryland; Laboratory of Applied Precision Omics, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, Maryland.
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.
Insights
Clinical antibody-mediated rejection (AMR) in lung transplants increases allograft failure risk. Subcategories of clinical AMR correlate with severity and death risk, but not failure risk.
Area of Science:
- Transplantation immunology
- Pulmonary medicine
- Graft rejection research
Background:
- Pulmonary antibody-mediated rejection (AMR) is categorized by diagnostic certainty.
- Recent consensus criteria define AMR categories, necessitating clinical feature and outcome analysis.
Purpose of the Study:
- To define clinical features and outcomes of recently defined pulmonary antibody-mediated rejection (AMR) categories.
- To assess the association between AMR diagnostic certainty and allograft outcomes.
Main Methods:
- Reviewed clinical data of 335 lung transplant recipients.
- Defined clinical/subclinical AMR based on allograft dysfunction and donor-derived cell-free DNA (ddcfDNA).
- Subcategorized clinical AMR as definite, probable, or possible based on characteristic features.
Main Results:
- Clinical AMR occurred in 28.7% of subjects, subclinical AMR in 18.5%.
- Clinical AMR demonstrated higher allograft failure risk and ddcfDNA levels than subclinical or no AMR.
- Definite/probable AMR showed greater severity and death risk than possible AMR, but similar failure risk.
Conclusions:
- Clinical AMR significantly increases allograft failure risk compared to subclinical or no AMR.
- AMR subcategorization by certainty correlates with severity and mortality, but not allograft failure risk.
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