title: Inter-individual differences in HLA expression can impact the CDC crossmatch.
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.
authors: Immunobiology Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland; Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors: G
authors: G
authors: Hönger
authors: N
authors: N
authors: Krähenbühl
authors: S
authors: S
authors: Dimeloe
authors: M
authors: M
authors: Stern
authors: S
authors: S
authors: Schaub
authors: C
authors: C
authors: Hess
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged
chemical_list: D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007126:Immunoglobulin Allotypes; D003165:Complement System Proteins
keywords: allo-reactivity; crossmatching; donor-specific human leucocyte antigen antibodies; human leucocyte antigen