title: Developments in the definition and clinical impact of human neutrophil antigens.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Muschter
authors.forename: Tom
authors.initials: T
authors.lastname: Berthold
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007519:Isoantigens / Q000235:genetics / Q000276:immunology*; D009503:Neutropenia / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D065227:Transfusion Reaction
chemical_list: D007519:Isoantigens