Developments in the definition and clinical impact of human neutrophil antigens

This review summarizes the current genetic, molecular and functional information on human neutrophil alloantigens (HNAs), which are implicated in autoimmune and alloimmune neutropenia and in transfusion-related acute lung injury. Identification and functional characterization of these antigens improve the understanding of HNA-antibody-induced diseases and may lead to the development of antibody detection assays and new therapeutic concepts.

HNA-3 is localized on choline transporter-like protein 2 (CTL2) and originates from an Arg154Gln amino acid (aa) substitution. The HNA-3a epitope is conformation sensitive. The additional single-nucleotide polymorphism (SNP) at aa 153 impairs genotyping and lowers the reactivity with some HNA-3a-antibodies. CD177 (HNA-2) interacts with PECAM-1, mediating neutrophil evasion. The percentage of the CD177-positive neutrophil subpopulation and the occurrence of two neutrophil subsets, differing in their CD177 expression, are associated with five SNPs. Glycosylphosphatidylinositol-linked CD177 anchors proteinase 3 on the cell membrane forming a potential signaling complex together with CD11b/CD18 (HNA-4a) in lipid rafts.

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).