TY - JOUR
T1 - Donor-specific HLA antibody-mediated complement activation is a significant indicator of antibody-mediated rejection and poor long-term graft outcome during lung transplantation
T2 - a single center cohort study
AU - Roux, Antoine
AU - Thomas, Kimberly A.
AU - Sage, Edouard
AU - Suberbielle-Boissel, Caroline
AU - Beaumont-Azuar, Laurence
AU - Parquin, Francois
AU - Le Guen, Morgan
AU - Harre, Nicholas
AU - Hamid, Abdul Monem
AU - Reed, Elaine F.
N1 - Funding Information:
This work was financially supported by both contributions from the “Association Gregory Lemarchal”, the “Fondation du souffle” and “Fondation Foch,” and funding from the NIH (R01 AI081249 and U01 AI124319 to EFR).
Funding Information:
The authors would like to thank the following members of the UCLA Immunogenetics Center: George Banzuela, Gertrudes Aguas, Gemalene Sunga, and Fadi Kandarian. In addition, this work was financially supported by both contributions from the “Association Gregory Lemar-chal”, the “Fondation du souffle” and “Fondation Foch,” and funding from the NIH (R01 AI081249 and U01 AI124319 to EFR).
Funding Information:
This work was financially supported by both contributions from the ?Association Gregory Lemarchal?, the ?Fondation du souffle? and ?Fondation Foch,? and funding from the NIH (R01 AI081249 and U01 AI124319 to EFR). The authors would like to thank the following members of the UCLA Immunogenetics Center: George Banzuela, Gertrudes Aguas, Gemalene Sunga, and Fadi Kandarian. In addition, this work was financially supported by both contributions from the ?Association Gregory Lemarchal?, the ?Fondation du souffle? and ?Fondation Foch,? and funding from the NIH (R01 AI081249 and U01 AI124319 to EFR).
Publisher Copyright:
© 2018 Steunstichting ESOT
PY - 2018/7
Y1 - 2018/7
N2 - 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.
AB - 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.
KW - antibody-mediated rejection
KW - complement
KW - donor-specific HLA antibodies
KW - lung transplant
UR - http://www.scopus.com/inward/record.url?scp=85045847857&partnerID=8YFLogxK
U2 - 10.1111/tri.13149
DO - 10.1111/tri.13149
M3 - Article
C2 - 29537702
AN - SCOPUS:85045847857
VL - 31
SP - 761
EP - 772
JO - Transplant International
JF - Transplant International
SN - 0934-0874
IS - 7
ER -