Jonathan Visentin1, Albane Chartier2, Layal Massara3, Gabriel Linares4, Gwendaline Guidicelli4, Elodie Blanchard2, Marie Parrens5, Hugues Begueret6, Claire Dromer2, Jean-Luc Taupin7. 1. Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; Unité Mixte de Recherche 5164, Centre National de la Recherche Scientifique, Université de Bordeaux, Talence, France. 2. Service des Maladies Respiratoires, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France. 3. Unité Mixte de Recherche 5164, Centre National de la Recherche Scientifique, Université de Bordeaux, Talence, France. 4. Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. 5. Laboratoire de Biologie et Pathologie des Tumeurs, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France; Département de Pathologie, A2406, Université de Bordeaux, Bordeaux, France. 6. Laboratoire de Biologie et Pathologie des Tumeurs, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France. 7. Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; Unité Mixte de Recherche 5164, Centre National de la Recherche Scientifique, Université de Bordeaux, Talence, France. Electronic address: jean-luc.taupin@aphp.fr.
Abstract
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 C1q 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 C1q-positive sDSAs, and 11 (20.8%) had gDSAs. Fifty sDSAs were found, among which 15 (30%) were C1q-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. Copyright Â
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 C1q 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 C1q-positive sDSAs, and 11 (20.8%) had gDSAs. Fifty sDSAs were found, among which 15 (30%) were C1q-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. Copyright Â
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