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 |
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| Authors: | 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 |
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| Affiliation: | 1. Pneumology, Adult CF Center and Lung Transplantation Department, Foch Hospital, Suresnes, France;2. Université Versailles Saint‐Quentin‐en‐Yvelines, Montigny le Bretonneux, France;3. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA;4. Thoracic Surgery Department, Foch Hospital, Suresnes, France;5. Laboratoire Régional d'Histocompatibilité, Saint‐Louis Hospital, Assistance Publique‐H?pitaux de Paris, Paris, France;6. Thoracic Intensive Care Unit, Foch Hospital, Suresnes, France;7. Anesthesiology Department, Foch Hospital, Suresnes, France |
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| 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 (DSAP osAMRP 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 ratioSUM ). DSAP osAMRP os patients had higher C3d ratioSUM 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 DSAP osAMRN eg patients. Specificity and calculated positive predictive value of the immunodominant C3d ratio and BCM sum 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 ratioSUM ≥10 or BCM sum >7000, suggesting that the antibody composition and/or strength are the principal determinants of an HLA DSA 's capacity to activate complement. |
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| Keywords: | antibody‐mediated rejection complement donor‐specific HLA antibodies lung transplant |
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