Molecular genetics of granulocyte polymorphisms

Abstract

Background and objectives: Granulocyte (neutrophil) antibodies have been implicated in transfusion-related acute lung injury (TRALI) and immune neutropenias. In the last decade enormous efforts have been made to characterize the involved alloantigens.

Materials and methods: Review of the literature.

Results: The NA1, NA2, and SH antigens have been identified as polymorphic forms of the neutrophil Fc gamma receptor IIIb encoded by three alleles. The antigens MART and OND have been located on leucocyte adhesion molecules (beta 2 integrins) and were found to be due to single nucleotide mutations in the alpha M (CD11b) and alpha L (CD11a) subunits. Recently, we succeeded in throwing light on the primary structure of the NB1 antigen. On the basis of these findings a new nomenclature has been introduced for human neutrophil alloantigens (HNA nomenclature). Glycoprotein location has made the development of antigen-specific immunoassays possible and antigen characterization on the molecular level now allows genotyping by DNA techniques.

Conclusion: Considerable progress has been made in the characterization of granulocyte antigens. Further studies will improve our diagnostic tools and will facilitate the prevention and management of transfusion reactions and immune neutropenias.