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Discovery of non-HLA antibodies associated with cardiac allograft rejection and development and validation of a non-HLA antigen multiplex panel: From bench to bedside.
Butler, Carrie L; Hickey, Michelle J; Jiang, Ning; Zheng, Ying; Gjertson, David; Zhang, Qiuheng; Rao, Ping; Fishbein, Gregory A; Cadeiras, Martin; Deng, Mario C; Banchs, Hector L; Torre, Guillermo; DeNofrio, David; Eisen, Howard J; Kobashigawa, Jon; Starling, Randall C; Kfoury, Abdallah; Van Bakel, Adrian; Ewald, Gregory; Balazs, Ivan; Baas, Arnold S; Cruz, Daniel; Ardehali, Reza; Biniwale, Reshma; Kwon, Murray; Ardehali, Abbas; Nsair, Ali; Ray, Bryan; Reed, Elaine F.
Affiliation
  • Butler CL; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
  • Hickey MJ; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
  • Jiang N; Immucor, Inc., Norcross, Georgia, USA.
  • Zheng Y; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
  • Gjertson D; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
  • Zhang Q; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
  • Rao P; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
  • Fishbein GA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
  • Cadeiras M; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  • Deng MC; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  • Banchs HL; Cardiovascular Center of Puerto Rico and the Caribbean Transplant Program, Carolina, Puerto Rico, USA.
  • Torre G; Houston Methodist Hospital Research Institution, Houston, Texas, USA.
  • DeNofrio D; Tufts Medical Center, Boston, Massachusetts, USA.
  • Eisen HJ; Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
  • Kobashigawa J; Cedars-Sinai Heart Institute, Los Angeles, California, USA.
  • Starling RC; Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA.
  • Kfoury A; Intermountain Medical Center, Salt Lake City, Utah, USA.
  • Van Bakel A; Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
  • Ewald G; Department of Medicine, Washington University, St. Louis, Missouri, USA.
  • Balazs I; Immucor, Inc., Norcross, Georgia, USA.
  • Baas AS; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  • Cruz D; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  • Ardehali R; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  • Biniwale R; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  • Kwon M; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  • Ardehali A; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  • Nsair A; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  • Ray B; Immucor, Inc., Norcross, Georgia, USA.
  • Reed EF; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Am J Transplant ; 20(10): 2768-2780, 2020 10.
Article in En | MEDLINE | ID: mdl-32185871
We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P < .5) from a discovery cohort of HLA antibody-negative, endothelial cell crossmatch-positive sera obtained from 12 cardiac allograft recipients at the time of biopsy-proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non-HLA antibodies associated with rejection (P < .1) including 4 newly identified non-HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non-HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non-HLA antigens synergize with HLA donor-specific antibodies and significantly increase the odds of rejection (P < .1). The non-HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, >1R) with an area under the curve of 0.87 (P < .05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non-HLA antibodies identifies cardiac transplant recipients at risk of rejection.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Heart Transplantation / Graft Rejection Type of study: Clinical_trials / Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Language: En Journal: Am J Transplant Journal subject: TRANSPLANTE Year: 2020 Type: Article Affiliation country: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Heart Transplantation / Graft Rejection Type of study: Clinical_trials / Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Language: En Journal: Am J Transplant Journal subject: TRANSPLANTE Year: 2020 Type: Article Affiliation country: United States