Distinct Levels of Human Anti-HLA Antibodies Induce Different Biological Effects in vitro on Human Umbilical Vein Endothelial Cells

Abstract

Objectives: Antibody-mediated rejection due to anti-donor HLA antibodies is a cause of chronic rejection and poor graft survival. The pathogenic role of these antibodies has been explained by their different effects on endothelial cells. Our objective was to study whether the levels of anti-HLA antibodies (measured by Luminex Single Antigen) in sera from alloimmunized patients correlate with the in vitro effects these antibodies induce on human umbilical vein endothelial cells. Material and methods:We explored the role of anti-HLA antibodies present in human serum on the proliferative potential of human umbilical vein endothelial cells (n = 17) and studied the expression of adhesion molecules (P-selectin) in these cells (n = 13). Results were correlated with the HLA antibody levels measured by Luminex. Results:The sera from alloimmunized patients inhibited endothelial cells proliferation and increased P-selectin expression compared to control sera (p < 0.0001 and p < 0.001, respectively). A relatively high level of anti-HLA antibodies was necessary to mediate the biological effects, with higher levels needed to affect proliferation (mean fluorescence intensity = 23,219) than to induce changes in P-selectin expression (mean fluorescence intensity = 13,170).Conclusions: These data add information on the value of the detection of anti-HLA antibodies by Luminex and could contribute to clarifying some aspects of the pathogenic mechanisms of antibody-mediated rejection.