Acute antibody-mediated rejection after lung transplantation

J Heart Lung Transplant. 2013 Oct;32(10):1034-40. doi: 10.1016/j.healun.2013.07.004. Epub 2013 Aug 13.


Background: Antibody-mediated rejection (AMR) after lung transplantation remains enigmatic, and there is no consensus on the characteristic clinical, immunologic and histologic features.

Methods: We performed a retrospective, single-center cohort study and identified cases of acute AMR based on the presence of circulating donor-specific human leukocyte antigen (HLA) antibodies (DSA), histologic evidence of acute lung injury, C4d deposition and clinical allograft dysfunction.

Results: We identified 21 recipients with acute AMR based on the aforementioned criteria. AMR occurred a median 258 days after transplantation; 7 recipients developed AMR within 45 days of transplantation. All patients had clinical allograft dysfunction, DSA, histology of acute lung injury and capillary endothelial C4d deposition. Fifteen recipients improved clinically and survived to hospital discharge, but 6 died of refractory AMR. One survivor had bronchiolitis obliterans syndrome at the time of AMR diagnosis; 13 of the 14 remaining survivors developed chronic lung allograft dysfunction (CLAD) during follow-up. Overall, 15 recipients died during the study period, and the median survival after the diagnosis of AMR was 593 days.

Conclusions: Acute AMR can be a fulminant form of lung rejection, and survivors are at increased risk of developing CLAD. The constellation of acute lung injury, DSA and capillary endothelial C4d deposition is compelling for acute AMR in recipients with allograft dysfunction. This clinicopathologic definition requires validation in a multicenter cohort, but may serve as a foundation for future studies to further characterize AMR.

Keywords: C4d deposition; acute antibody-mediated rejection; chronic lung allograft dysfunction; donor specific antibodies; human leukocyte antigen antibodies; lung transplantation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antibodies / immunology*
  • Antibodies / physiology*
  • Cohort Studies
  • Complement C4b / metabolism
  • Female
  • Graft Rejection / epidemiology*
  • Graft Rejection / immunology*
  • Graft Rejection / physiopathology
  • HLA Antigens / immunology
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Peptide Fragments / metabolism
  • Pulmonary Disease, Chronic Obstructive / surgery
  • Pulmonary Fibrosis / surgery
  • Retrospective Studies
  • Risk Factors


  • Antibodies
  • HLA Antigens
  • Peptide Fragments
  • Complement C4b
  • complement C4d