Molecular nature of granulocyte antigens

Granulocyte (neutrophil) antibodies can cause febrile and pulmonary (TRALI) transfusion reactions as well as immune neutropenias. In the last decade enormous efforts have been made to characterize the implicated alloantigens. The NA1, NA2, and SH antigens could be identified as polymorphic forms of the neutrophil Fc gammaReceptor IIIb encoded by three alleles. The antigens MART and OND have been located on the leucocyte adhesion molecules (beta2 integrins) and found to be caused by single nucleotide mutations in the alphaM (CD11b) and alphaL (CD11a) subunits. We have succeeded in throwing light on the primary structure of the NB1 antigen, which has recently been clustered as CD177. Based on these findings, the Granulocyte Antigen Working Party of the ISBT introduced in 1998 a new nomenclature for human neutrophil alloantigens (HNA nomenclature) based on the antigen's glycoprotein location. Elucidation of the molecular nature of granulocyte antigens now allows antigen identification by glycoprotein-specific immunoassays and genotyping by DNA techniques. Thus, considerable progress has been made in the characterization of granulocyte antigens. Further studies will improve our diagnostic tools and facilitate the prevention and management of transfusion reactions and immune neutropenias.