title: Banff study of pathologic changes in lung allograft biopsy specimens with donor-specific antibodies.
abstract: BACKGROUND
  The diagnosis of antibody-mediated rejection (AMR) in the lung transplant is still an area under investigation. We performed a blinded multicenter study to determine if any statistically significant histologic findings in transbronchial biopsy specimens from lung transplant patients correlate with the presence of donor-specific antibodies (DSAs).
  
  
  METHODS
  We asked 9 pathologists with experience in lung transplantation to evaluate 161 lung transplant biopsy specimens for various histologic parameters. The findings were correlated with antibody status positive for DSAs, positive for non-DSAs, and no antibodies (NABs) present. The significance of each histologic variable was reviewed.
  
  
  RESULTS
  We found no statistically significant association with acute cellular rejection, airway inflammation, or bronchiolitis obliterans and the presence or absence of antibodies. However, biopsy specimens with DSAs had a statistically significant difference vs NABs in the setting of acute lung injury, with or without diffuse alveolar damage (p = 0.0008), in the presence of capillary neutrophilic inflammation (p = 0.0014), and in samples with endotheliitis (p = 0.0155). In samples with complement 4d staining, there was a trend but no statistically significant difference between specimens associated with DSAs and specimens with NABs.
  
  
  CONCLUSIONS
  Capillary inflammation, acute lung injury, and endotheliitis significantly correlated with DSAs. The infrequently observed diffuse staining for complement 4d limits the usefulness of this stain.
authors.affiliation: Department of Pathology, University of California, Los Angeles Medical Center, Los Angeles California. Electronic address: wwallace@mednet.ucla.edu.
authors.forename: William Dean
authors.initials: WD
authors.lastname: Wallace
authors.affiliation: Department of Biomathematics, University of California, Los Angeles Medical Center, Los Angeles California.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Pathology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Claus B
authors.initials: CB
authors.lastname: Andersen
authors.affiliation: Department of Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: A Valeria
authors.initials: AV
authors.lastname: Arrossi
authors.affiliation: Department of Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Medhat
authors.initials: M
authors.lastname: Askar
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, California.
authors.forename: Gerry J
authors.initials: GJ
authors.lastname: Berry
authors.affiliation: Department of Pathology, University of California, Los Angeles Medical Center, Los Angeles California.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: DeNicola
authors.affiliation: Department of Histopathology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.
authors.forename: Desley A
authors.initials: DA
authors.lastname: Neil
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Pavlisko
authors.affiliation: Department of Pathology, University of California, Los Angeles Medical Center, Los Angeles California.
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
authors.affiliation: Department of Pathology, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Remmelink
authors.affiliation: Division of Pulmonology, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
authors.forename: S Sam
authors.initials: SS
authors.lastname: Weigt
authors.affiliation: Department of Pathology, Catholic University of Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Birgit
authors.initials: B
authors.lastname: Weynand
authors.affiliation: Department of Pathology, University of California, Los Angeles Medical Center, Los Angeles California.
authors.forename: Jennifer Q
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: Pulmonary Medicine, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Marie M
authors.initials: MM
authors.lastname: Budev
authors.affiliation: Department of Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Carol F
authors.initials: CF
authors.lastname: Farver
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D001706:Biopsy; D001989:Bronchiolitis Obliterans / Q000601:surgery*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D007518:Isoantibodies
keywords: acute lung injury; antibody-mediated rejection; biopsy specimen; capillary inflammation; donor-specific antibodies; endotheliitis; lung transplant