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

G Hönger1, N Krähenbühl, S Dimeloe

  • 1Immunobiology Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland; Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.

Tissue Antigens
|March 20, 2015
PubMed
Summary

Human leucocyte antigen (HLA) expression on lymphocytes is stable within individuals but varies significantly between people. This variability impacts in vitro cytotoxicity testing, including complement-dependent cytotoxicity (CDC) assays.

Keywords:
allo-reactivitycrossmatchingdonor-specific human leucocyte antigen antibodieshuman leucocyte antigen

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Area of Science:

  • Immunology
  • Transplantation Immunology

Background:

  • The relationship between human leucocyte antigen (HLA) expression on lymphocytes and in vitro cytotoxicity testing outcomes is not well-defined.
  • Understanding this relationship is crucial for interpreting the results of immunological assays used in clinical settings, such as transplantation.

Purpose of the Study:

  • To investigate how HLA expression levels on human lymphocytes correlate with clinically relevant in vitro cytotoxicity testing.
  • To assess the intra-individual and inter-individual variability of HLA expression on lymphocytes.

Main Methods:

  • Semi-quantitative assessment of HLA expression on lymphocytes (CD4+ T-cells, CD8+ T-cells, and B-cells) in cross-sectional (n=14) and longitudinal (n=6) studies.
  • Evaluation of complement-dependent cytotoxicity (CDC) and cellular allo-reactivity against target cells with defined HLA expression levels.

Main Results:

  • Intra-individual HLA levels showed limited variation (≤1.5-fold) on T-cells and B-cells.
  • Significant inter-individual variability in HLA expression was observed (2.07- to 2.90-fold).
  • HLA-A2 expression levels directly impacted CDC crossmatch reactions and cytotoxicity mediated by HLA-A2-reactive effector cells.

Conclusions:

  • Human HLA expression on lymphocytes is stable within individuals but shows substantial inter-individual variation.
  • Variability in HLA expression levels can significantly influence in vitro functional cytotoxic reactions, notably the CDC crossmatch assay.
  • Further prospective studies are needed to establish the clinical significance of these findings in transplantation and other immunological contexts.