Original article

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Neonatal alloimmune neutropenia: diagnosis and management of 31 Italian patients

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Key words: neutropenia, newborns, human neutrophil alloantibodies
Publication Date: 2022-08-05

Abstract

Background - In neonates, antibody-mediated destruction of neutrophils may occur as a consequence of auto- or isoimmune disorders. There are few studies on this topic, and particularly on neonatal alloimmune neutropenia (NAN).
Materials and methods - We retrospectively evaluated the clinical and molecular/serological findings of 83 neutropenic infants referred to our Reference Laboratory for diagnostic evaluation of NAN, from 2008 to 2021. We also genotyped 260 Italian healthy subjects for the four principal human neutrophil antigens (HNA).
Results - The diagnosis of NAN was confirmed in 31 cases. The other 52 cases were autoimmune neutropenia (n=21), neutropenia caused by maternal neutrophil autoantibodies (n=8), neutropenia of non-immune origin (n=17), and cases in which a diagnosis could not be reached (n=6). The median age at neutropenia onset and absolute neutrophil count (ANC) were significantly lower in NAN than in non-NAN cases (1 vs 30 days, p<0.005; 330 vs 580/μL, p=0.003, respectively). About 74% of NAN cases developed neutropenia within the first week of life and laboratory investigations were required within 2 weeks. In five patients the neutropenia was discovered at the end of the first month of life and they were referred to our laboratory 1-2 months later when neutropenia had already resolved. Infections were seen in 19% of NAN cases. The median time to resolution of NAN was 31 days. About 50% of NAN cases were due to alloantibodies against HNA-1b, the most frequent allele of HNA-1 in the Italian population (allele frequency 0.63). In five cases of NAN the mothers had an HNA-1 null phenotype, a frequency higher than that observed in our Italian cohort.
Discussion - NAN should be considered by clinicians in infants with neutropenia onset within 5-7 days of life, even though there can be other reasons for a low ANC. If neutropenia is detected later, benign neutropenia seems more likely, although persistence of maternal alloantibodies cannot be ruled out.

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Authors

Alessandra Cattaneo - Flow Cytometry Service, Clinical Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

Manuela Liguori - Flow Cytometry Service, Clinical Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

Elena Trombetta - Flow Cytometry Service, Clinical Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

Ferruccio Ceriotti - Flow Cytometry Service, Clinical Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

Lorenza Pugni - Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

Andrea Ronchi - Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

Giulia Carracchia - Pediatric Oncohematology and Bone Marrow Transplant Unit, Children's Hospital, ASST Spedali Civili of Brescia, Brescia, Italy

Lucia D. Notarangelo - Medical Direction, Children's Hospital, ASST Spedali Civili of Brescia, Brescia, Italy

Francesca Ferrua - Pediatric Immunohematology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

Federica Barzaghi - Pediatric Immunohematology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

Chiara Giovanettoni - Neonatal Intensive Care Unit, ASST Rhodense- Presidio di Rho, Milan, Italy

Gianvincenzo Zuccotti - Department of Biomedical and Clinical Science "L. Sacco" Ospedale dei Bambini, University of Milan, Italy

Emilia Cirillo - Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Naples, Italy

Claudio Pignata - Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Naples, Italy

Federica Meroni - Neonatal Intensive Care Unit, Hospital A. Manzoni, Lecco, Italy

Anna Maietta - Neonatal Intensive Care Unit, University Hospital “Luigi Vanvitelli”, Naples, Italy

Piero Farruggia - Pediatric Hematology and Oncology Unit, Oncology Department, A.R.N.A.S. Ospedale Civico Di Cristina e Benfratelli, Palermo, Italy

Laura Porretti - Flow Cytometry Service, Clinical Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy;

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