Abstract
Severe transfusion-related acute lung injury (TRALI) is often due to antibodies in blood components directed against human neutrophil antigen (HNA)-3a. This study aimed to report the genotype frequencies of the HNA-3 system and to estimate the potential risk of HNA-3 incompatibility and alloimmunization in two Thai populations. Eight hundred DNA samples obtained from 500 unrelated healthy blood donors at the National Blood Centre, Thai Red Cross Society, Bangkok and 300 samples from the Blood Bank, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand were included. HNA-3 genotyping was performed using an in-house polymerase chain reaction with sequence-specific primer (PCR-SSP) technique. The observed frequencies of the HNA-3a/3a, HNA-3a/3b, and HNA-3b/3b genotypes were 0.528, 0.380, and 0.092 in central Thais and 0.600, 0.350, and 0.050 in northern Thais, respectively. The frequencies were used to estimate HNA-3 incompatibility and risk of HNA-3a alloimmunization. The HNA-3 incompatibility in central Thais (33.28%) was higher than northern Thais (28.75%), corresponding to a significantly higher probability of HNA-3a alloimmunization (P<0.05) similar to Japanese and Chinese populations. This study showed the high risk of HNA-3 incompatibility and alloimmunization, especially in central Thai blood donors. A molecular-based identification of the HNA-3 genotype of female donors is suggested to reduce the risk of TRALI following plasma and whole blood allogeneic transfusion.
Highlights
Alloantibodies against human neutrophil alloantigens (HNA) can be formed during pregnancy or transfusion of blood components and are associated with neonatal alloimmune neutropenia, febrile transfusion reactions and transfusion-related acute lung injury (TRALI) [1]
To validate the polymerase chain reaction with sequence-specific primer (PCR-SSP) technique, 19 samples were sequenced to SNPs c.461G>A and c.457C>T and the results showed c.461G in all HNA-3a individuals, c.461A in all HNA-3b individuals and c.461G/A in all HNA-3a/3b individuals, while none of the 19 samples carried SNP c.457T
HNA-3a alloantibodies found in donor plasma directed against recipient’s neutrophils can cause severe and fatal TRALI [2,3,4]
Summary
Alloantibodies against human neutrophil alloantigens (HNA) can be formed during pregnancy or transfusion of blood components and are associated with neonatal alloimmune neutropenia, febrile transfusion reactions and transfusion-related acute lung injury (TRALI) [1]. The HNA-3 antigens are associated with a biallelic polymorphism caused by a single nucleotide polymorphism, SNP (c.461G>A; p.Arg154Gln) in the choline transporter like protein-2 (CTL-2, Gene SLC44A2) [3,4]. This finding leads to DNA-based HNA-3 genotyping by polymerase chain reaction with sequence-specific primer (PCR-SSP), widely used to determine genotypes as HNA-3a/3a, HNA-3a/3b, and HNA-3b/3b, respectively [12]. A recent study in Thai blood donors reported that the gene frequencies of HNA-3a and HNA-3b were 0.490 and 0.510, respectively and HNA-3a/3b individuals were the most common; the SNP c.457C>T mutation was not determined [11]
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