Clinical Outcomes of Lung Transplantation in the Presence of Donor-Specific Antibodies

Ann Am Thorac Soc. 2019 Sep;16(9):1131-1137. doi: 10.1513/AnnalsATS.201812-869OC.

Abstract

Rationale: There is significant variation in approach to pre-lung transplant donor-specific antibodies (DSA), with some centers declining to cross any DSA. We implemented a protocol for transplantation for candidates with pretransplant DSA so long as a prospective complement-dependent cytotoxicity crossmatch was negative, regardless of number, specificity, class, or mean fluorescence intensity.Objectives: To compare post-transplant outcomes including overall survival, chronic lung allograft dysfunction-free survival, antibody-mediated rejection, and acute cellular rejection in lung transplant recipients where pretransplant DSA was and was not present.Methods: This was a single-center retrospective cohort study. For recipients with pretransplant DSA, if the prospective complement-dependent cytotoxicity crossmatch was negative, the donor offer was accepted and plasmapheresis was performed within 24 hours of transplantation and continued until retrospective crossmatch results returned. Immunosuppression and post-transplant management were not otherwise modified.Results: Of the 203 included recipients, 18 (8.9%) had pretransplant DSA. The median DSA mean fluorescence intensity was 4,000 (interquartile range, 2,975-5,625; total range, 2,100-17,000). The median number of DSA present per patient was one (interquartile range, 1-2). The presence of pretransplant DSA was not associated with increased mortality (hazard ratio, 1.2; 95% confidence interval [CI], 0.4-3.4) or decreased chronic lung allograft dysfunction-free survival (hazard ratio, 1.1; 95% CI, 0.6-2.1). Recipients with pretransplant DSA were more likely to require prolonged mechanical ventilation (adjusted odds ratio, 7.0; 95% CI, 2.3-21.6) and to have antibody-mediated rejection requiring treatment (adjusted odds ratio, 7.5; 95% CI, 1.0-55.8).Conclusions: A protocol of accepting donor offers for lung transplant candidates with preformed, complement-dependent cytotoxicity crossmatch-negative DSA is associated with increased need for prolonged mechanical ventilation and antibody-mediated rejection without affecting short-term overall or chronic lung allograft dysfunction-free survival.

Keywords: antibody-mediated rejection; chronic lung allograft dysfunction; donor-specific antibodies; lung transplantation.

MeSH terms

  • Aged
  • Boston
  • Female
  • Graft Rejection / epidemiology
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Survival
  • HLA Antigens / immunology*
  • Histocompatibility Testing
  • Humans
  • Isoantibodies / immunology*
  • Lung Transplantation / adverse effects*
  • Lung Transplantation / mortality
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • Tissue Donors*
  • Treatment Outcome

Substances

  • HLA Antigens
  • Isoantibodies