Nowadays, five antigen systems are defined on human granulocytes. They are named as "Human Neutrophil Antigens" or "HNA"-1 to -5. The first characterization of a neutrophil specific antigen was made by Lalezari in 1960, who described a case of Neonatal Immune Neutropenia (NIN) caused by "NA1" ("Neutrophil Antigen 1", today HNA-1a). This antigen is located on the clinically most important immunogenic glycoprotein of the neutrophil, Fc gamma receptor IIIb (CD16b). There are two further antigens located on this receptor, HNA-1b and HNA-1c. Neutrophil autoantibodies bind preferably to granulocytes expressing the HNA-1a antigen.
|antigen||old nomenclature||localisation||frequency %||comment|
|Fcγ Rezeptor IIIb = CD16b||58
|HNA-2a||NB1||NB1 GP = CD177||97||granulocyte-specific|
|HNA-3a||5b||GP 70-95||97||also expressed on lymphocytes|
|HNA-5a||Ond||CD11a||92||also expressed on lymphocytes|
HNA-2a, the former NB1, is also located on a granulocyte-specific glycoprotein, CD177. Its exact function is still unknown, but recent studies revealed that CD177 acts as a counterreceptor for endothelial PECAM-1 (CD31) and therefore might be involved in neutrophil transmigration (Sachs et al., J Biol Chem 2007;282:23603-23612). A special feature of this antigen is its heterogeneic expression, i.e. there are two subpopulations of granulocytes in one individual, HNA-2a-positive and HNA-2a-negative granulocytes, respectively.
Antibodies against HNA-3a, the former 5b, are often detected in cases of severe transfusion-associated acute lung injury (TRALI). The molecular basis of this antigen is still subject of research. HNA-4a and HNA-5a are high frequency antigens localized on integrins. They are results of single nucleotide polymorphisms. Antibodies directed against the proteins coded by the antithetic alleles were not described so far.