Inter-individual differences in HLA expression can impact the CDC crossmatch

Research output: Contribution to journalArticlepeer-review

Authors

  • G Hoenger
  • N Kraehenbhuel
  • M Stern
  • S Schaub
  • Christoph Hess

Colleges, School and Institutes

Abstract

How human leucocyte antigen (HLA) expression levels on human lymphocytes relate to clinically relevant in vitro cytotoxicity testing has not been defined. Here, cross-sectional (n = 14) and longitudinal (n = 6) semi-quantitative assessment of HLA expression on lymphocytes was performed. Complement-dependent cytotoxicity (CDC) and cellular allo-reactivity were assessed vis-à-vis target cells with defined levels of HLA expression. On CD4(+) and CD8(+) T-cells, and on B-cells, intra-individual HLA levels varied ≤1.5-fold, whereas inter-individual HLA expression varied 2.34-fold and 2.07-fold on CD4(+) and CD8(+) T-cells, respectively, and 2.90-fold on B-cells. Importantly, CDC crossmatch reactions induced by anti-HLA-A2 monoclonal antibody as well as patient sera solely containing HLA-A2 antibodies were significantly impacted by HLA-A2 expression levels on donor cells. Likewise, cytotoxicity of HLA-A2 reactive effector cells was induced proportionate to availability of HLA-A2. These data demonstrate that human HLA expression on lymphocytes from healthy blood donors is fairly stable intra-individually, yet varies significantly from person to person. Variability in HLA expression levels can impact functional cytotoxic reactions in vitro, including the widely used CDC crossmatch assay. Prospective studies are required to test the clinical relevance of this finding.

Details

Original languageEnglish
Pages (from-to)260-266
Number of pages7
JournalTissue Antigens
Volume85
Issue number4
Early online date19 Mar 2015
Publication statusPublished - Apr 2015

Keywords

  • allo-reactivity, crossmatching, donor-specific human leucocyte antigen antibodies, human leucocyte antigen

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