The complexity of human leukocyte antigen (HLA)-DQ antibodies and its effect on virtual crossmatching

Transplantation. 2010 Nov 27;90(10):1117-24. doi: 10.1097/TP.0b013e3181f89c6d.

Abstract

Background: We previously reported that in patients possessing human leukocyte antigen (HLA)-DQ-directed antibodies, the target molecule may include the patient's own DQβ chain if it is paired with non-self-DQα chain, thus forming a different DQ target. Herein, we sought to assess the breadth of this phenomenon.

Methods: Serum samples from 104 patients awaiting kidney transplantation, known to have DQ antibodies, were studied. Antibody identification was performed using luminex-based HLA class II single-antigen bead assays from two vendors; DQA1/DQB1 typing was performed using luminex polymerase chain reaction - sequence specific oligo prob hybridization (PCR-SSO) technology.

Results: A total of 71% of the 104 serum samples studied contained antibodies reactive against test beads coated with the patient's own DQα- or β-chain components. Of those, 35 patients (34%) exhibited antibodies to their own DQβ chain when in combination with non-self-DQα chains; and 64 patients (62%) had antibodies to their own DQα chain when in combination with non-self-DQβ chains. This is a striking observation.

Conclusions: To the best of our knowledge, this is the first systematic, high-resolution evaluation of DQ antibody repertoire. With the expansion of virtual crossmatching, particularly in the context of a national registry, the need for more detailed DQ antibody or antigen evaluation is critical to improve operational efficiency and patient outcomes.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Autoantibodies / immunology
  • Autoantigens / chemistry
  • Autoantigens / genetics
  • Autoantigens / immunology
  • Epitopes / chemistry
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • HLA-DQ Antigens / chemistry
  • HLA-DQ Antigens / genetics
  • HLA-DQ Antigens / immunology*
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • Histocompatibility Testing
  • Humans
  • Isoantibodies / immunology*
  • Kidney Transplantation / immunology
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Models, Molecular
  • User-Computer Interface
  • Young Adult

Substances

  • Autoantibodies
  • Autoantigens
  • Epitopes
  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQbeta antigen
  • Isoantibodies