Shinji Otani1, Amanda K Davis2, Linda Cantwell3, Steven Ivulich4, Alan Pham5, Miranda A Paraskeva1, Greg I Snell1, Glen P Westall6. 1. Lung Transplant Service, Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Australia. 2. Department of Hematology, The Alfred Hospital, Melbourne, Australia. 3. National Transplant Services, Australian Red Cross Blood Services, Melbourne, Australia. 4. Pharmacy Department, The Alfred Hospital, Melbourne, Australia. 5. Department of Anatomical Pathology, The Alfred Hospital, Melbourne, Australia. 6. Lung Transplant Service, Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Australia. Electronic address: G.Westall@alfred.org.au.
Abstract
BACKGROUND: The importance of antibody-mediated rejection (AMR) following lung transplantation remains contentious. In particular, the diagnostic criteria suggested to define AMR, namely the presence of donor-specific antibodies (DSA), C4d immunoreactivity, histological features and allograft dysfunction are not always readily applicable or confirmatory in lung transplantation. METHODS: In a retrospective single-center study of 255 lung transplant recipients (LTR), we identified 9 patients in whom a clinical diagnosis of AMR was made within 12months of transplant, and define the immunological, histological, clinical features, as well as the therapeutic response of this cohort. RESULTS: Nine LTR with AMR underwent combination therapy with high-dose intravenous corticosteroid, intravenous immunoglobulin, plasmapheresis and rituximab. Following therapy, while the total number of the original DSA dropped by 17%, and the median value of the mean fluorescence intensity (mfi) of the originally observed DSA decreased from 5292 (IQR 1319-12,754) to 2409 (IQR 920-6825) (p<0.001), clinical outcomes were variable with a number of patients progressing to either chronic lung allograft dysfunction or death within 12month. CONCLUSION: AMR in lung transplantation remains both a diagnostic and therapeutic challenge, but when clinically suspected is associated with a variable response to therapy and poor long-term outcomes.
BACKGROUND: The importance of antibody-mediated rejection (AMR) following lung transplantation remains contentious. In particular, the diagnostic criteria suggested to define AMR, namely the presence of donor-specific antibodies (DSA), C4d immunoreactivity, histological features and allograft dysfunction are not always readily applicable or confirmatory in lung transplantation. METHODS: In a retrospective single-center study of 255 lung transplant recipients (LTR), we identified 9 patients in whom a clinical diagnosis of AMR was made within 12months of transplant, and define the immunological, histological, clinical features, as well as the therapeutic response of this cohort. RESULTS: Nine LTR with AMR underwent combination therapy with high-dose intravenous corticosteroid, intravenous immunoglobulin, plasmapheresis and rituximab. Following therapy, while the total number of the original DSA dropped by 17%, and the median value of the mean fluorescence intensity (mfi) of the originally observed DSA decreased from 5292 (IQR 1319-12,754) to 2409 (IQR 920-6825) (p<0.001), clinical outcomes were variable with a number of patients progressing to either chronic lung allograft dysfunction or death within 12month. CONCLUSION: AMR in lung transplantation remains both a diagnostic and therapeutic challenge, but when clinically suspected is associated with a variable response to therapy and poor long-term outcomes.
Authors: Ramsey R Hachem; Malek Kamoun; Marie M Budev; Medhat Askar; Vivek N Ahya; James C Lee; Deborah J Levine; Marilyn S Pollack; Gundeep S Dhillon; David Weill; Kenneth B Schechtman; Lorriana E Leard; Jeffrey A Golden; LeeAnn Baxter-Lowe; Thalachallour Mohanakumar; Dolly B Tyan; Roger D Yusen Journal: Am J Transplant Date: 2018-05-15 Impact factor: 8.086
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