title: HLA-DQ barrier: effects on cPRA calculations.
abstract: BACKGROUND
  Panel-reactive antibody (PRA) testing provides assessment of the breadth of sensitization a patient might have against human leukocyte antigen (HLA) antigens. The evolution of calculated PRA (cPRA) reflects the commitment of the transplant community to increase accessibility and promote equity to all patients awaiting kidney transplantation. Recent data from our center and others, however, suggested that a significant diversity of HLA-DQ antigens is not captured, which may lead to inequity in allocating cPRA points.
  
  
  METHODS
  HLA-DRB1-DQA1-DQB1 typing of 2182 individuals was evaluated for this study using Luminex-based sequence-specific oligonucleotide typing. A total of 3182 haplotypes were confirmed to have the level of resolution required for this study.
  
  
  RESULTS
  The diversity of HLA-DQαβ alleles is greater than what is apparent using the serologic equivalents. The distribution of these alleles within a serologic group varies, with some alleles being more frequent than others; therefore, their representation within the current cPRA system is inaccurate. Three informative examples are given. Haplotypes of DR antigens with DQαβ alleles did not always follow the common published linkage disequilibrium, especially in populations where there is greater genetic diversity.
  
  
  CONCLUSIONS
  The current cPRA system does not take into account the distribution of molecular equivalents within DQ serologic specificities. This can result is inequitable allocation of sensitization points and disadvantaging the more sensitized patients. To ameliorate this situation, the United Network for Organ Sharing system should allow inputting HLA-DQαβ alleles both for donor typing and as antibody specificities, which will lead to better representation of unacceptable DQ alleles and improve organ allocation equity.
authors.affiliation: 1 Transplant Immunology Laboratory, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL. 2 Department of Surgery, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL. 3 Department of Internal Medicine, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL. 4 Address correspondence to: Anat R. Tambur, D.M.D., Ph.D., D[ABHI], Transplant Immunology Laboratory, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: Anat R
authors.initials: AR
authors.lastname: Tambur
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Leventhal
authors.forename: R Carlin
authors.initials: RC
authors.lastname: Walsh
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Zitzner
authors.forename: John J
authors.initials: JJ
authors.lastname: Friedewald
mesh_terms: D000465:Algorithms; D000483:Alleles; D000906:Antibodies / Q000276:immunology*; D014644:Genetic Variation; D006683:HLA-DQ Antigens / Q000235:genetics*; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D016130:Immunophenotyping; D015810:Linkage Disequilibrium; D009841:Oligonucleotides; D016377:Organ Transplantation; D009927:Tissue and Organ Procurement / Q000592:standards
chemical_list: D000906:Antibodies; D006683:HLA-DQ Antigens; D009841:Oligonucleotides