Clinical Implications of Human Neutrophil Antigens

As neutrophils are central components of human immune system, they play significant clinical roles including fields of transfusion and transplantation. Antibodies (auto-, iso- and allo- antibodies) cognate to neutrophil antigens can cause a range of severe complications precisely including neutropenia, febrile nonhemolytic transfusion reaction (FNHTR), transfusion related alloimmune neutropenia (TRAIN), transfusion related acute lung injury (TRALI), post - transplant neutropenia and delayed engraftment

Alloimmune conditions

Here is a complete list of possible alloimmune clinical complications caused by antibodies against HNAs

  • Neonatal alloimmune neutropenia (NAN)

  • Transfusion-related acute lung injury (TRALI)

  • Alloimmune neutropenia after bone marrow transplantation

  • Transfusion-related alloimmune neutropenia (TRAIN)

  • Refractoriness to granulocyte transfusion

  • Febrile transfusion reactions

Neonatal alloimmune neutropenia is one of the potentially fatal alloimmune conditions where there arises an incompatibility between maternal and fetal neutrophil antigens. This condition is caused when maternal antibodies cognate to paternal antigens in fetus leading to profound absence of neutrophils thereby imparing the innate immunity of the newborn making them highly susceptible to infections and sepsis.

TRALI, one of the leading causes of transfusion-associated deaths is clinically often characterized by sudden onset of dypsnea either during the course of transfusion or within 6 hours post transfusion. Reports states that this condition is associated with considerable morbidity in about 6-10% of the cases. Interaction of antibodies in donor plasma against recipient WBC antigens is the major trigger, where in majority (89%) of cases antibodies are found agaianst HLA class I and granulocyte specific antigens. There exists handful of evidence describing fatal cases of TRALI due to transfusion of donor plasma containing antibodies against HNA-3a antigens.

Autoimmune conditions

Here is a complete list of possible autoimmune clinical complications caused by antibodies against HNAs

  • Autoimmune neutropenia of childhood

  • Drug-induced immune neutropenia

  • Autoimmune neutropenia after bone marrow transplantation

Autoimmune neutropenia (AIN) is a childhood condition where individual produces antibodies against membrane antigens on their own neutrophils. It is often a secondary condition that arises due to other factors including immunological, viral, bacterial and malignancy. Although primary AIN is extremely rare among adults, handful of case reports have been reported till date.

Details of the alloantibodies against various classes of human neutrophil antigens and their clinical implications are provided in the file in further sections.