title: The DQ barrier: improving organ allocation equity using HLA-DQ information.
abstract: BACKGROUND
  The United Network for Organ Sharing algorithm for deceased-donor kidney allocation considers only the human leukocyte antigen (HLA)-A, HLA-B, and HLA-DR loci. Although HLA-DQ serologic specificities can be entered as unacceptable antigens, they are assigned only by the identity of the DQβ chain, disregarding the role of the similarly polymorphic α chain. DQα/β combinations result in unique antigenic epitopes, which serve as targets to different antibodies. Therefore, the presence of HLA antibodies to one DQα/β combination should not preclude negative crossmatch (XM) against another combination. In this retrospective analysis, patients were allowed XM against a particular donor if they had antibodies to some, but not all, DQα/β allele combinations with the donor serologic HLA-DQ antigens.
  
  
  METHODS
  HLA antibody signature was obtained using solid-phase Luminex-based antibody analysis. Results were captured at the high-resolution level (as provided by the positive beads). Potential donors were typed to include information on both HLA-DQA and HLA-DQB alleles.
  
  
  RESULTS
  Of the 1130 flow XM assays performed, 147 patients had antibodies to donor serologic HLA-DQ antigens. Thirty-five of those patients had antibodies to an allelic DQα/β combination within the donor serologic DQ specificity that were different from the donor's DQα/β, leading to negative flow XM results (24%). Virtual XM, accounting for donor DQα/β combinations, successfully predicts more than 98% of XM outcomes.
  
  
  CONCLUSIONS
  In patients with allelic DQα/β antibodies, denying the opportunity for XM based on serologically defined unacceptable antigens can disadvantage the patient. Larger cohort studies are required to substantiate our observation. Introducing DQα/β combination information may increase virtual XM accuracy and organ allocation equity.
authors.affiliation: Transplant Immunology Laboratory, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Tarry Building Suite 11-711, Chicago, IL 60611-3008, USA. a-tambur@northwestern.edu
authors.forename: Anat R
authors.initials: AR
authors.lastname: Tambur
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Leventhal
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Zitzner
authors.forename: R Carlin
authors.initials: RC
authors.lastname: Walsh
authors.forename: John J
authors.initials: JJ
authors.lastname: Friedewald
mesh_terms: D000368:Aged; D000465:Algorithms; D046148:Donor Selection; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006683:HLA-DQ Antigens / Q000276:immunology*; D059848:HLA-DQ alpha-Chains / Q000276:immunology; D059866:HLA-DQ beta-Chains / Q000276:immunology; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D016377:Organ Transplantation / Q000009:adverse effects*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013997:Time Factors; D023001:Transplantation Tolerance; D016896:Treatment Outcome
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D007518:Isoantibodies