Antibodies to human neutrophil antigen HNA‐3b implicated in cases of neonatal alloimmune neutropenia

Abstract

BACKGROUND Neonatal alloimmune neutropenia results from maternal alloimmunization to human neutrophil antigens. The alloantibodies involved in neonatal alloimmune neutropenia are against human neutrophil antigens HNA‐1a, HNA‐1b, HNA‐1c, HNA‐1d, HNA‐2, HNA‐3a, HNA‐4a, HNA‐4b, and HNA‐5a; however, to date, antibodies specific to HNA‐3b have not been reported. STUDY DESIGN AND METHODS Blood samples from 10,000 unselected neonates were analyzed, resulting in the selection of 88 neutropenic newborns (neutrophil count <1.5 × 109/L) from 83 mothers (three pairs of twins and one triplet). HNA‐3 genotyping was performed by polymerase chain reaction‐restriction fragment length polymorphism to identify the cases of maternal‐fetal HNA‐3 incompatibility. Serologic studies for detecting maternal HNA‐3 alloantibodies were performed with the granulocyte agglutination test, the white blood cell immunofluorescence test, and a LABScreen Multi‐HNA Kit. RESULTS Genotyping studies identified 13 of 88 (14.8%) instances of maternal‐fetal HNA‐3 incompatibility, with all mothers typed as HNA‐3a/a and neonates typed as HNA‐3a/b. Serologic studies revealed that five of 13 (38.5%) mothers carried anti‐HNA‐3b plus human leukocyte antigen antibodies and that three of 13 (23.1%) mothers had anti‐HNA‐3b without human leukocyte antigen antibodies. CONCLUSION Here, we report the first three cases of neonatal alloimmune neutropenia associated with HNA‐3b antibodies resulting in a neonatal alloimmune neutropenia incidence of one in 3333 live births.

Neonatal Alloimmune Neutropenia

“…The other antibody specificities are only rarely detected. Cases of NAIN due to maternal anti-HNA-1c, anti-HNA-1d, anti-HNA-3a, anti-HNA-3b, anti-HNA-4b, and anti-HNA-5a antibodies have been described in rare case reports [16,24,25,42,43,44,45]. Antibodies against HNA-5b have never been detected.…”

Serologic and molecular studies to identify neonatal alloimmune neutropenia in a cohort of 10,000 neonates

“…Besides that, the presence of mutations in other regions of the CTL2 protein may alter the affinity of the antibody 20 . Therefore, considering the technical problems observed with the HNA‐3 system, GAT is still considered the gold‐standard test for anti‐HNA‐3 detection 12,19 …”

“…GAT 16 and Flow‐WIFT 17,18 assays were performed as previously described, with minor modifications, using a specific panel of three blood donors previously genotyped for HNA systems. Additionally, for positive anti‐HNA‐3b results, mothers’ sera were tested by GAT with another three different neutrophil subjects, genotyped homozygous for HNA‐3b/b 12 . The blood donors’ genotyping is described in Table I.…”

“…More rarely, antibodies are against HNA‐1c, HNA‐1d, HNA‐3a, HNA‐3b, HNA‐4a, HNA‐4b and HNA‐5a. No NAIN case has been associated with anti‐HNA‐5b 12,13 …”

Human neutrophil antigen allele frequencies and assessment of HNA alloimmunisation risk in donors and hematological patients

“…Несмотря на высокий расчетный риск аллоиммунизации к HNA-3b, описаны редкие случаи АНН, вызванной аллоантителами анти-HNA-3b, и в литературе не встречаются данные о случаях ОТОПЛ, вызванного такими антителами. Наиболее частой причиной развития АНН в популяции белых европейцев являются аллоантитела к HNA-1а, -1b, -1c и -2а [16], однако в литературе описаны случаи АНН, вызванной аллоантителами к HNA-1d, -3а, -3b, -4а, -4b, -5а [17,18]. В клинической практике трансфузии гранулоцитного концентрата осуществляют пациентам при значительном снижении абсолютного количества гранулоцитов в крови при наличии инфекции, неконтролируемой антибактериальной терапией, а также при сепсисе новорожденных.…”