Donor-specific HLA antibody-mediated complement activation is a significant indicator of antibody-mediated rejection and poor long-term graft outcome during lung transplantation: a single center cohort study

Antoine Roux, Kimberly A. Thomas, Edouard Sage, Caroline Suberbielle-Boissel, Laurence Beaumont-Azuar, Francois Parquin, Morgan Le Guen, Nicholas Harre, Abdul Monem Hamid, Elaine F. Reed

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Complement-mediated allograft injury, elicited by donor-specific HLA antibodies (DSA), is a defining pathophysiological characteristic of allograft damage. We aimed to study DSA-induced complement activation as a diagnostic marker of antibody-mediated rejection (AMR) and a risk stratification tool for graft loss in the context of lung transplantation (LT). We identified 38 DSA-positive patients whose serum samples were submitted for C3d deposition testing via the C3d assay. Among these 38 patients, 15 had AMR (DSA P os AMR P os ). Results were reported for each patient as the C3d ratio for each DSA, the immunodominant DSA, and the C3d ratio for all DSA present in a sample (C3d ratio SUM ). DSA P os AMR P os patients had higher C3d ratio SUM values (58.66 (−1.32 to 118.6) vs. 1.52 (0.30 to 2.74), P = 0.0016) and increased immunodominant C3d ratios (41.87 (1.72 to 82.02) vs. 0.69 (0.21 to 1.19), P = 0.001) when compared with DSA P os AMR N eg patients. Specificity and calculated positive predictive value of the immunodominant C3d ratio and BCMsum tests for AMR diagnosis were both 100% (CI = 17.4–100) in this cohort. Worst graft survival was associated with both immunodominant C3d ratio ≥4 or C3d ratio SUM ≥10 or BCMsum >7000, suggesting that the antibody composition and/or strength are the principal determinants of an HLA DSA's capacity to activate complement.

Original languageEnglish
Pages (from-to)761-772
Number of pages12
JournalTransplant International
Volume31
Issue number7
DOIs
StatePublished - Jul 2018

Keywords

  • antibody-mediated rejection
  • complement
  • donor-specific HLA antibodies
  • lung transplant

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