Lung intragraft donor-specific antibodies as a risk factor for graft loss

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:35

Article

Visentin, Jonathan^1,2  Chattier, Albane³  Massara, Layal²  Linares, Gabriel¹  Guidicelli, Gwendaline¹  Blanchard, Elodie³  Parrens, Marie^4,5  Begueret, Hugues⁴  Dromer, Claire³  Taupin, Jean-Luc^1,2 

[1] Ctr Hosp Univ Bordeaux, Lab Immunol & Immunogenet, Hop Pellegrin, Bordeaux, France

[2] Univ Bordeaux, CNRS, Unite Mixte Rech 5164, Talence, France

[3] Ctr Hosp Univ Bordeaux, Serv Malad Resp, Hop Haut Leveque, Pessac, France

[4] Ctr Hosp Univ Bordeaux, Lab Biol & Pathol Tumeurs, Hop Haut Leveque, Pessac, France

[5] Univ Bordeaux, Dept Pathol, A2406, Bordeaux, France

关键词: HLA antibodies;    lung transplant;    single-antigen flow beads;    biopsy;    antibody-mediated rejection;   

DOI  :  10.1016/j.healun.2016.06.010

来源: Elsevier

【 摘 要 】

BACKGROUND: The effect of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) on graft survival is recognized in lung transplantation, but not all serum DSAs appear to be harmful. We wondered whether in situ DSA detection from graft biopsy specimens could help in identifying lung transplant recipients (LTRs) at higher risk for graft loss. METHODS: Class I and II HLA antibody single-antigen flow bead assays were performed in 53 LTRs to identify immunoglobulin G DSA in biopsy specimen eluates and in sera and to evaluate Clq binding ability of DSA in sera. Intragraft DSAs (gDSAs) were correlated with serum DSAs (sDSAs), clinical and histologic data, and graft survival. RESULTS: Twenty-eight (52.8%) LTRs had sDSAs, 12 (22.6%) had Clq-positive sDSAs, and 11 (20.8%) had gDSAs. Fifty sDSAs were found, among which 15 (30%) were Clq-positive and 14 (28%) were found in biopsy specimen eluates. One DSA was detected in the biopsy specimen only. Serum mean fluorescence intensity and biopsy fragment size were higher for sDSAs detected in biopsy specimens (p = 0.003 and p = 0.02, respectively). One-year post-biopsy graft survival was lower for LTRs with gDSAs (p = 0.008 by log-rank test). Presence of gDSA at the time of biopsy constituted a risk factor for graft loss in univariate (odds ratio, 6.67; 95% confidence interval [CI] 1.51-29.47; p = 0.008; hazard risk, 3.44; 95% CI, 1.47-8.01, p = 0.005) and multivariate (odds ratio, 5.85; 95% CI, 1.23-27.68; p = 0.03; hazard risk, 4.51; 95% CI, 1.83-11.13; p = 0001) analyses using logistic regression and a Cox proportional hazard model, respectively. CONCLUSIONS: In lung transplantation, gDSA appears to be a valuable biomarker to identify pathogenic DSA and LTRs with a higher risk for graft loss. (C) 2016 International Society for Heart and Lung Transplantation. All rights reserved.

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