Serologic and molecular studies to identify neonatal alloimmune neutropenia in a cohort of 10, 000 neonates. (2nd February 2021)

• Record Type: Journal Article
• Authors: Abbas, Samira A.; Lopes, Larissa B.; Moritz, Elyse; Martins, Juliana O.; Chiba, Akemi K; Kunioshi, Alessandra M.; Barbosa, Elisama S.; Langhi Junior, Dante M.; dos Santos, Amélia M. N.; Godinho, Cárlei H.; Bordin, José O.
• Is Part Of: British journal of haematology. Volume 192:Number 4(2021)
• Page Start: 778
• Page End: 784
• Publication Date: 2021-02-02
• Subjects: Anti‐HNA‐1d -- Anti‐HNA‐3b -- maternal‐fetal HNA incompatibility -- neonatal alloimmune neutropenia -- neutrophil alloimmunisation; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.17295
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: Neonatal alloimmune neutropenia (NAIN) is caused by maternal alloimmunisation to fetal human neutrophil antigens (HNAs). This study investigated maternal HNA/HLA alloantibodies involved with NAIN and identified the frequency of NAIN in Brazilian neonates. Neonatal neutropenia (neutrophil count < 1.5 × 10 9 /L) was investigated in samples from 10, 000 unselected neonates, resulting in 88 neutropenic newborns (NBs) and their 83 mothers. Genotyping was performed by PCR‐SSP (HNA‐1/‐4) and PCR‐RFLP (HNA‐3/‐5). Serologic studies were performed by GAT (granulocyte agglutination test), Flow‐WIFT (white blood cells immunofluorescence test) and LABScreen‐Multi‐HNA‐Kit (OneLambda®) (LSM). Neonatal neutropenia was identified in 88/10, 000 (0·9%) NBs. Genotyping revealed 60·2% maternal‐fetal HNA incompatibilities (31·8% for HNA‐1; 14·8% for HNA‐3; 15·9% for HNA‐4; 21·6% for HNA‐5). Serologic studies revealed 37·3% of mothers with positive results with at least one technique. The detected anti‐HNA specificities were confirmed in eight positive cases related to HNA‐1/‐3 systems. In cases with maternal‐fetal HNA‐4/‐5 incompatibility, no specific neutrophil alloantibodies were found but anti‐HLA I/II were present. Anti‐HNA‐2 was not identified. This is a large Brazilian study which involved the investigation of antibodies against all five HNA systems in neutropenia cases and showed a frequency of NAIN in 8/10, 000 neonates. Among the HNA antibodies identified, we highlight the anti‐HNA‐1d and anti‐HNA‐3b, antibodies unusual in alloimmunised women, and rarely related to NAIN cases.