Human Neutrophil Antigen Genotype and Allele Frequencies in Iranian Blood Donors

Objective Human neutrophil antigens (HNAs) can be targeted by HNA-allo antibodies and cause a variety of clinical conditions such as transfusion-related acute lung injury (TRALI) and neonatal alloimmune neutropenia (NAIN). The current study is aimed at identifying the genotype and allele frequencies of HNAs in Iranian blood donors. Methods A total of 150 blood samples were obtained from healthy blood donors. HNA-1, HNA-3, HNA-4, and HNA-5 were genotyped, using the polymerase chain reaction sequence-specific primer (PCR-SSP) technique. The expression of the HNA-2 antigen on the neutrophil surface was evaluated by flow cytometry. Results The allele frequencies of FCGR3B∗1 (encoding HNA-1a), FCGR3B∗2 (encoding HNA-1b), and FCGR3B∗3 (encoding HNA-1c) were 0.34, 0.63, and 0.03, respectively. For HNA-3, the allele frequencies for SLC44A2∗1 (encoding HNA-3a) and SLC44A2∗2 (encoding HNA-3b) were 0.63 and 0.37, respectively. The frequencies of ITGAM∗1 (encoding HNA-4a) and ITGAM∗2 (encoding HNA-4b) alleles were 0.85 and 0.15, respectively. Furthermore, the frequencies of ITGAL∗1 (encoding HNA-5a) and ITGAL∗2 (encoding HNA-5b) alleles were 0.72 and 0.28, respectively. In the studied population, HNA-2 antigen was present on the neutrophil surface in 97.3% of the individuals, while no detectable HNA-2 expression was observed in 2.7% of the individuals. However, no significant difference in HNA-2 expression between different age groups was found. Conclusion The present study provides the first report of the HNA allele and genotype frequencies among the Iranian population. All HNAs (HNA-1 to HNA-5) were typed using the PCR-SSP and flow cytometer. In the current cohort study, the determined HNA allele frequencies were similar to the previous reports from British, German, and Danish populations. Considering the presence of different Iranian ethnic groups, further studies with a larger sample size are needed to draw a total picture for HNA allele frequencies.

[1]  R. Dearman,et al.  Human neutrophil antigens: Nature, clinical significance and detection , 2020, International journal of immunogenetics.

[2]  G. Chambers,et al.  Human neutrophil antigen frequency data for Malays, Chinese and Indians. , 2020, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[3]  B. Flesch Work‐up in the case of granulocyte antibodies , 2020, ISBT Science Series.

[4]  B. Bayat Molecular basis of human neutrophil antigen 2 (HNA‐2) expression , 2020, ISBT Science Series.

[5]  H. Kroll,et al.  Genotyping of human neutrophil antigens 1, 3, 4 and 5 using a novel multiplex polymerase chain reaction , 2019, Transfusion medicine.

[6]  J. Kwok,et al.  A study of human neutrophil antigen genotype frequencies in Hong Kong , 2018, Transfusion medicine.

[7]  O. Nathalang,et al.  Flow-Cytometric Analysis of HNA-2 Expression and Phenotypes Among Thai Blood Donors , 2018, Annals of laboratory medicine.

[8]  P. Lalezari Neutrophil‐specific antigens, immunobiology, and implications in transfusion medicine and blood disorders , 2017, Transfusion.

[9]  M. Shaiegan,et al.  The allele frequencies of human Neutrophil Antigens 5 (HNA-5) in Tabriz city , 2017 .

[10]  F. Nadali,et al.  Molecular evaluation of Human Neutrophil Antigen (HNA-3) in some blood donors , 2016 .

[11]  G. Bein,et al.  A sequence‐specific polymerase chain reaction method for HNA‐2 genotyping: homozygous c.843A>T mutation predicts the absence of CD177 , 2016, Transfusion.

[12]  B. Curtis,et al.  Update on the nomenclature of human neutrophil antigens and alleles , 2016, Transfusion.

[13]  M. Majbouri,et al.  Iran’s Multi-ethnic Mosaic: A 23-Year Perspective , 2016 .

[14]  Yunfang Li,et al.  Genetic Mechanism of Human Neutrophil Antigen 2 Deficiency and Expression Variations , 2015, PLoS genetics.

[15]  B. Flesch Human neutrophil antigens: a nomenclature update based on new alleles and new antigens , 2015 .

[16]  O. Nathalang,et al.  Human neutrophil alloantigen genotype frequencies in Thai blood donors. , 2014, Blood transfusion = Trasfusione del sangue.

[17]  C. Navarrete,et al.  Determination of human neutrophil antigen‐1, ‐3, ‐4 and ‐5 allele frequencies in English Caucasoid blood donors using a multiplex fluorescent DNA‐based assay , 2013, Vox sanguinis.

[18]  N. Tsuno,et al.  The frequencies of human neutrophil alloantigens among the Japanese population. , 2012, Tissue antigens.

[19]  R. Steffensen,et al.  Frequencies of HNA-1, HNA-3, HNA-4, and HNA-5 in the Danish and Zambian populations determined using a novel TaqMan real time polymerase chain reaction method. , 2012, Tissue antigens.

[20]  D. Stroncek,et al.  Frequencies of SLC44A2 alleles encoding human neutrophil antigen‐3 variants in the African American population , 2012, Transfusion.

[21]  T. Dengler,et al.  Human neutrophil alloantigen genotype frequencies among blood donors with Turkish and German descent. , 2011, Tissue antigens.

[22]  Yongshui Fu,et al.  The frequencies of human neutrophil alloantigens in the Chinese Han population of Guangzhou , 2011, Transfusion.

[23]  F. Costa,et al.  Molecular studies reveal that A134T, G156A and G1333A SNPs in the CD177 gene are associated with atypical expression of human neutrophil antigen‐2 , 2010, Vox sanguinis.

[24]  J. Bordin,et al.  Human neutrophil alloantigen-1a, -1b, -2, -3a and -4a frequencies in Brazilians. , 2009, Tissue antigens.

[25]  E. Muñiz‐Díaz,et al.  HNA-1a, HNA-1b and HNA-1c gene frequencies in Argentineans. , 2008, Tissue antigens.

[26]  D. Stroncek,et al.  Expression of human neutrophil antigen‐2a (NB1) is increased in pregnancy , 2003, Transfusion.

[27]  K. Kissel,et al.  Molecular basis of NB1 (HNA-2a, CD177) deficiency. , 2002, Blood.

[28]  Masao Kobayashi,et al.  Human neutrophil antigen‐2a expression on neutrophils from healthy adults in western Japan , 2002, Transfusion.

[29]  R. Siebert,et al.  FCGR3 variants and expression of human neutrophil antigen‐1a, ‐1b, and ‐1c in the populations of northern Germany and Uganda , 2002, Transfusion.

[30]  K. Kissel,et al.  HNA-1a, HNA-1b, and HNA-1c (NA1, NA2, SH) frequencies in African and American Blacks and in Chinese. , 2000, Tissue antigens.

[31]  D. Stroncek,et al.  Variations in the expression of granulocyte antigen NB1 , 2000, Transfusion.

[32]  H. Wulf,et al.  Transfusion-related lung injury with leukopenic reaction caused by fresh frozen plasma containing anti-NB1. , 1999, Anesthesiology.

[33]  T. Um,et al.  Frequency of neutrophil-specific antigens among Koreans using the granulocyte indirect immunofluorescence test (GIFT) , 1997, Immunohematology.

[34]  D. Stroncek,et al.  Prolonged neutropenia resulting from antibodies to neutrophil‐specific antigen NB1 following marrow transplantation , 1993, Transfusion.

[35]  P. Lalezari,et al.  Autoimmune neutropenia of infancy. , 1986, The Journal of pediatrics.

[36]  P. Lalezari,et al.  NB1, a new neutrophil-specific antigen involved in the pathogenesis of neonatal neutropenia. , 1971, The Journal of clinical investigation.