title: Optimizing transplantation of sensitized heart candidates using 4 antibody detection assays to prioritize the assignment of unacceptable antigens.
abstract: BACKGROUND
  The virtual crossmatch relies on the assignment of unacceptable antigens (UAs) to identify compatible donors. The purpose of our study was to identify an algorithm for assignment of UAs such that a negative complement-dependent cytotoxicity (CDC) crossmatch and concomitant negative or weakly positive flow cytometric crossmatch (FXM) are obtained.
  
  
  METHODS
  We used 4 antibody methods: (1) Luminex single antigen (LSA), (2) LSA with a 1:8 serum dilution, (3) C1q LSA, and (4) CDC panel. The UAs were prioritized in the following order: (1) all C1q+/CDC+, (2) LSA 1:8 >7,500 median fluorescence intensity, and (3) LSA >10,000 median fluorescence intensity.
  
  
  RESULTS
  Of 295 heart transplants that were performed at our center, 69 (23%) recipients had detectable human leukocyte antigen specific antibody at the time of transplant. All donor specific antibodies (DSAs) were avoided for 44 of 69 (64%) (DSA-). There were 25 recipients who had DSA at the time of transplant: 12 (48%) had negative FXM (DSA+/FXM-), and 13 (52%) had positive T-cell and/or B-cell FXM (DSA+/FXM+). Lower freedom from antibody-mediated rejection was observed for the DSA+/FXM+ group compared with the DSA- group (p < 0.0001). DSA remained detectable after transplant in the sera of 14 recipients, and de novo DSA was detected in 32 recipients. Freedom from antibody-mediated rejection was comparable for both groups (p = 0.53) but was lower than the DSA- group (p < 0.0001). Survival was comparable for all groups at 1,200 days post-transplant.
  
  
  CONCLUSIONS
  Strategic prioritization of UA assignment has allowed transplantation of highly sensitized patients across the DSA barrier with survival rates comparable to DSA- heart transplant recipients.
authors.affiliation: HLA and Immunogenetics Laboratory. Electronic address: reinsmoenn@cshs.org.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Reinsmoen
authors.affiliation: Cedars-Sinai Heart Institute.
authors.forename: Jignesh
authors.initials: J
authors.lastname: Patel
authors.affiliation: Biostatistics Core, Research Institute, Clinical and Translational Science Institute, Clinical and Translational Research Center, Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: James
authors.initials: J
authors.lastname: Mirocha
authors.affiliation: HLA and Immunogenetics Laboratory.
authors.forename: Chih-hung
authors.initials: CH
authors.lastname: Lai
authors.affiliation: HLA and Immunogenetics Laboratory.
authors.forename: Mehrnoush
authors.initials: M
authors.lastname: Naim
authors.affiliation: HLA and Immunogenetics Laboratory.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Ong
authors.affiliation: HLA and Immunogenetics Laboratory.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: HLA and Immunogenetics Laboratory.
authors.forename: Xiaohai
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Cedars-Sinai Heart Institute.
authors.forename: Frank
authors.initials: F
authors.lastname: Liou
authors.affiliation: Cedars-Sinai Heart Institute.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Cedars-Sinai Heart Institute.
authors.forename: Jon
authors.initials: J
authors.lastname: Kobashigawa
mesh_terms: D000465:Algorithms; D003888:Desensitization, Immunologic; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000032:analysis*; D016027:Heart Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy; D007518:Isoantibodies / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology*; D011182:Postoperative Care; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: C1q; CDC; CPRA; heart transplant; solid phase antibody testing; unacceptable antigen