The Human Neutrophil Antigen Resource - a comprehensive collection of information on human neutrophil antigens and their clinical applications

Mercy Rophina
02 May 2022

A dose of history

Human blood is a lifeline fluid which comprises four major components namely the red blood cells (erythrocytes), white blood cells (leukocytes), platelets and plasma. Significant research and insights are available on the erythrocyte antigens. Although not all, antigens of major blood groups like ABO and RH are very well aware owing to their severe clinical consequences. In the early years of the 20th century, the attention of the scientific community was directed towards leukocytes ever since agglutination of leukocytes in patient sera was observed. This gradually led to the discovery and exploration of the human leukocyte antigen (HLA) system. It was back in 1960, antigens specifically expressed on the surface of neutrophils were identified and the human neutrophil antigens (HNA) system was established in 1999.

Why are human neutrophil antigens important?

As neutrophils are central components of the human immune system, they play significant clinical roles in the field of transfusion and transplantation medicine. 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 (Chapman et al., 2009),(Mraz et al., 2016).

Exploration of the genetic underpinnings

There are officially five groups/systems, HNA-1 through to HNA-5, consisting of fourteen officially assigned alleles. The genes underlying their molecular mechanisms were identified as FCGR3B, CD177, SLC44A2, ITGAM and ITGAL, respectively. The current nomenclature of HNA - encoding alleles and antigens were recommended and published by the International Society of Blood Transfusion - Granulocyte Immunobiology Working Party (ISBT - GIWP). Nomenclature for the allele names comprises the official gene name followed by an asterisk and a two digit numeric specifying the allele number. For example, FCGR3B*01.

Genetic epidemiology - a key to awareness

Owing to their polymorphic nature, deeper understanding of ethnicity specific differences in HNA genotypes has become the need of the hour. Only a handful of studies have performed serology based estimation of HNA allele frequencies on a population scale (Esmaeili et al., 2022),(Nguyen et al., 2009). As population-scale genome programmes accelerate in pace across the world, a quick analysis using the 1000 Genomes Project and gnomAD data revealed that there exists significant variability in HNA variants among the global populations. One of the best examples which could be possibly stated is the ITGAL_16:30506720G>C variant of HNA class 5, whose frequency was 71.4% in South Asians, 13.4% in East Asians, 30.1% in Europeans, 42.1% in Africans and 18.9% in Americans. Analyzing genomic data of many other populations which were under-represented in major global sequencing projects, would help create a clearer picture of the inter-population differences.

What do we provide?

Efforts to estimate the prevalence of genetic variations underpinning the antigenic expression are emerging. However, there lacks a precise capture of the global frequency profiles. There lies immense potential utility of maintaining an organized online repository of evidence on neutrophil antigen associated genetic variants from published literature and reports. So, here we introduce The Human Neutrophil Antigen Resource - a comprehensive collection of information on human neutrophil antigens and their clinical applications. This resource elaborates the history, nomenclature system, classifications and potential clinical implications of HNAs. This collection has a total of 37 genomic variants encompassing the five major HNA classes and is available at https://hunar.genomes.in/. This in our opinion, is an emerging area and would significantly benefit from the awareness and understanding of population-level diversities.

Related Resources

The Human Neutrophil Antigen Resource - https://hunar.genomes.in/

Mercy Rophina, Vinod Scaria
Genetic epidemiology of human neutrophil antigen variants suggest significant global variability
bioRxiv 2022.04.28.489826; doi: https://doi.org/10.1101/2022.04.28.489826

References

Chapman, C. E., Stainsby, D., Jones, H., Love, E., Massey, E., Win, N., Navarrete, C., Lucas, G., Soni, N., Morgan, C., Choo, L., Cohen, H., Williamson, L. M., & Serious Hazards of Transfusion Steering Group. (2009). Ten years of hemovigilance reports of transfusion-related acute lung injury in the United Kingdom and the impact of preferential use of male donor plasma. Transfusion, 49(3), 440–452.

Esmaeili, B., Bayat, B., Alirezaee, A., Delkhah, M., Mehdizadeh, M. R., & Pourpak, Z. (2022). Human Neutrophil Antigen Genotype and Allele Frequencies in Iranian Blood Donors. Journal of Immunology Research, 2022, 4387555.

Mraz, G. A., Crighton, G. L., & Christie, D. J. (2016). Antibodies to human neutrophil antigen HNA-4b implicated in a case of neonatal alloimmune neutropenia. In Transfusion (Vol. 56, Issue 5, pp. 1161–1165). https://doi.org/10.1111/trf.13463

Nguyen, X. D., Flesch, B., Sachs, U. J., Kroll, H., Klüter, H., & Müller-Steinhardt, M. (2009). Rapid screening of granulocyte antibodies with a novel assay: flow cytometric granulocyte immunofluorescence test. Transfusion, 49(12), 2700–2708.