Neutrophil Antigen Genetics and Transfusion Immunology

Human neutrophil antigens (HNAs) are a set of genetically defined polymorphic proteins expressed on the surface of neutrophils. These antigens are encoded by distinct gene families, including FCGR3B (HNA-1), CD177 (HNA-2), SLC44A2 (HNA-3) and the integrin subunits ITGAM (HNA-4) and ITGAL (HNA-5). Allelic variation at these loci gives rise to antigenic diversity that can provoke alloimmune responses when incompatible blood components are transfused or during pregnancy. Alloantibody formation against HNAs may lead to transfusion-related acute lung injury (TRALI), neonatal alloimmune neutropenia (NAIN) or refractoriness to granulocyte transfusions. Advances in molecular genotyping—ranging from sequence-specific primer PCR to high-throughput single nucleotide polymorphism (SNP) arrays and droplet digital PCR—have improved the resolution of antigen typing, enabling risk stratification in donors and recipients. Population studies reveal marked differences in HNA allele frequencies across ethnic groups, informing selection of compatible donors and guiding preventive strategies. Concurrent investigation of HNA genetics and human leukocyte antigen (HLA) associations has shed light on susceptibility to autoimmune neutropenias. Together, these developments underpin tailored transfusion protocols, enhanced diagnostics for antibody identification and improved management of alloimmune complications in both adult and neonatal settings.

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Neutrophil Antigen Genetics and Transfusion Immunology publication trend

The graph below shows the total number of articles in neutrophil antigen genetics and transfusion immunology across all publications each year (not limited to Nature Index journals).

Technical terms

Neutrophil alloantigen: A polymorphic surface protein on neutrophils that can elicit an immune response when mismatched in transfusion or pregnancy.

HNA system: Classification of human neutrophil antigens into serological groups (HNA-1 to HNA-5) defined by underlying genetic polymorphisms.

Transfusion-related acute lung injury (TRALI): A serious pulmonary complication following transfusion, mediated by donor antibodies against recipient neutrophil antigens.

Neonatal alloimmune neutropenia (NAIN): A condition in which maternal antibodies target fetal neutrophil antigens, causing neutrophil destruction in the neonate.

Single nucleotide polymorphism (SNP): A single-base variation in the genome that can alter antigenic epitopes and drive HNA diversity.

TaqMan real-time PCR: A probe-based assay enabling real-time detection and quantification of specific DNA sequences, used for allele discrimination.

Droplet digital PCR (ddPCR): A highly sensitive method partitioning PCR reactions into microdroplets to quantify DNA variants with precise allele frequency measurements.

References

1. Human neutrophil alloantigens systems. Anais da Academia Brasileira de Ciências (2009).
2. Human Neutrophil Antigen Genotype and Allele Frequencies in Iranian Blood Donors. Journal of Immunology Research (2022).
3. SLC44A2 Frequency, a New TaqMan Real-Time Polymerase Chain Reaction Method for HNA-3A/3B Genotyping, and a New Application of Droplet Digital PCR. Frontiers in Genetics (2022).
4. HNA specificity and association to HLA-DRB1 and -DQB1 in patients with autoimmune neutropenia of early childhood. Clinical Immunology Communications (2023).