Human Neutrophil Antigens

Human Neutrophil Antigens (HNAs) are expressed on five different glycoproteins (GP) on neutrophils. The HNA system comprises five antigen systems HNA-1 to HNA-5. HNA-1 is expressed on GP FcγRIIIb (CD16b) and comprises HNA-1a, -1b, -1c and -1d. HNA-2 is an iso-antigen on CD177, i.e. patients either express it or all null. HNA-3 is expressed on the choline-transporter-like protein 2 (CTL2) and is the only HNA antigen expressed on tissue other than neutrophils, including on kidney endothelium. HNA-3 comprises HNA-3a and -3b. HNA-4 is expressed on CD11b and comprises HNA-4a and -4b. HNA-5 is expressed on CD11a and comprises HNA-5a and -5b.

HNA to GP Mapping:

Antigen Glycoprotein
HNA-1 -1a, -1b, -1c, -1d FcγRIIIb aka CD16b
HNA-2 CD177
HNA-3 -3a, -3b CTL2
HNA-4 -4a, -4b CD11b
HNA-5 -5a, -5b CD11a

Antibodies directed against these antigens are implicated in a number of conditions, including:

  • Transfusion-related acute lung injury (TRALI)
  • Neonatal alloimmune neutropenia (NAIT)
  • Febrile non-haemolytic transfusion reactions (FNHTR)
  • Autoimmune neutropenia
  • Immune neutropenia after bone marrow transplant

H&I laboratory tests used for the detection of HNA antibodies include the granulocyte agglutination test (GAT), the granulocyte immunofluorescence test (GIFT), Monoclonal antibody immobilisation of granulocyte antigens (MAIGA) and HNA typing.