Characterization of the HNA-3 system allows identification of blood donors at risk to develop HNA-3-antibodies. FcγRIIIb (HNA-1) and CD177 (HNA-2) seem to be important in bacterial host defense. Activation of neutrophils by HNA-1 and HNA-2-antibodies potentially occurs via mPR3 and CD11b/CD18 (HNA-4a).
Binding of HNA-3a alloantibodies depends on the conformation of the intact CTL2 protein and their binding sites may differ substantially. Peptide-based assays for detection of HNA-3a antibodies bear the risk to be insensitive and require systematic validation with a large panel of antibodies.
This study provides experimental evidence supporting the "threshold model" of TRALI. Priming of neutrophils with fMLP or LPS increases their aggregation response to HNA-3a antibodies by lowering the required antibody amount.
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