title: Evolving experience of treating antibody-mediated rejection following lung transplantation.
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.
  
  
  CONCLUSIONS
  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.affiliation: Lung Transplant Service, Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Australia.
authors.forename: Shinji
authors.initials: S
authors.lastname: Otani
authors.affiliation: Department of Hematology, The Alfred Hospital, Melbourne, Australia.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Davis
authors.affiliation: National Transplant Services, Australian Red Cross Blood Services, Melbourne, Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Cantwell
authors.affiliation: Pharmacy Department, The Alfred Hospital, Melbourne, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Ivulich
authors.affiliation: Department of Anatomical Pathology, The Alfred Hospital, Melbourne, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Pham
authors.affiliation: Lung Transplant Service, Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Australia.
authors.forename: Miranda A
authors.initials: MA
authors.lastname: Paraskeva
authors.affiliation: Lung Transplant Service, Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Australia.
authors.forename: Greg I
authors.initials: GI
authors.lastname: Snell
authors.affiliation: Lung Transplant Service, Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Australia. Electronic address: G.Westall@alfred.org.au.
authors.forename: Glen P
authors.initials: GP
authors.lastname: Westall
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D064591:Allografts / Q000276:immunology*; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D007165:Immunosuppression Therapy; D008168:Lung / Q000276:immunology / Q000601:surgery; D016040:Lung Transplantation; D008297:Male; D010956:Plasmapheresis; D012189:Retrospective Studies; D000069283:Rituximab; D014019:Tissue Donors
chemical_list: D000305:Adrenal Cortex Hormones; D000906:Antibodies; D058846:Antibodies, Monoclonal, Murine-Derived; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000069283:Rituximab
keywords: Antibody-mediated rejection; Bronchiolitis obliterans syndrome; Chronic lung allograft syndrome; Lung transplantation; Plasmapheresis; Rituximab