Banff study of pathologic changes in lung allograft biopsy specimens with donor-specific antibodies

J Heart Lung Transplant. 2016 Jan;35(1):40-48. doi: 10.1016/j.healun.2015.08.021. Epub 2015 Sep 25.

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.

Keywords: acute lung injury; antibody-mediated rejection; biopsy specimen; capillary inflammation; donor-specific antibodies; endotheliitis; lung transplant.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allografts
  • Biopsy
  • Bronchiolitis Obliterans / surgery*
  • Female
  • Graft Rejection / immunology*
  • Graft Rejection / pathology
  • Humans
  • Isoantibodies / immunology*
  • Lung / immunology
  • Lung / pathology*
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Tissue Donors*
  • Young Adult

Substances

  • Isoantibodies