Concurrent neonatal alloimmune neutropenia and thrombocytopenia: Prevalence and antibody specificity and intensity in a large Brazilian cohort.

Abstract

Background: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) and neonatal alloimmune neutropenia (NAIN) result from maternal alloantibodies targeting fetal human platelet antigen (HPA) and human neutrophil antigen (HNA) antigens, respectively. However, increasing evidence supports the pathogenic role of HLA class I alloantibodies in these conditions. Since the simultaneous occurrence of FNAIT and NAIN has not been systematically investigated, this study aimed to determine its prevalence, characterize the specificity and strength of associated alloantibodies, and correlate findings with neonatal cell counts.

Study design and methods: In this cross-sectional study, 10,000 umbilical cord blood samples were analyzed for platelet and neutrophil counts. Neonates with thrombocytopenia and neutropenia were selected. Genotyping for HPA, HNA, and HLA class I was performed in mother-infant pairs to assess incompatibilities. Maternal sera were tested for anti-HPA, anti-HNA, and anti-HLA antibodies.

Results: Ten cases (0.1%) of concurrent cytopenias were identified. Alloantibodies were detected in four cases: one with combined anti-HPA-5b, HNA-2, and HLA-A2 antibodies; and three with isolated high-mean fluorescence intensity (MFI) HLA antibodies (anti-HLA-A2, HLA-A3, HLA-B7). Anti-HLA-A2 was linked to the lowest neutrophil counts, and anti-HLA-B7 to severe thrombocytopenia. The estimated prevalence of simultaneous FNAIT and NAIN was 0.04% (1 in 2500 neonates).

Discussion: This is the first large-scale study to document the co-occurrence of FNAIT and NAIN. Our findings explore the serological and molecular features of these immune syndromes and underscore the potential pathogenic role of maternal anti-HLA class I antibodies, even in the absence of detectable anti-HPA or anti-HNA, and support including HLA testing in the diagnostic workup of neonatal cytopenias.