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

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.