Alloimmune neonatal neutropenia linked to anti‐HNA‐4a

Fung, Yoke Lin; Pitcher, L.; Willett, J E; Reed, Christopher; Mison, L; Bux, J.; Eiber, Gail; Minchinton, R. M.

doi:10.1046/j.1365-3148.2003.00413.x

Cited by 41 publications

(47 citation statements)

References 20 publications

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“…It is not known whether the function of the CD11b/CD18 complex is influenced by the polymorphism [3]. HNA-4a alloantibodies that interfere with CD11b/Mac-1-dependent neutrophil adhesion can induce NIN [96]. Interestingly, antibodies of the same specificity that do not exhibit this functional characteristic were not able to induce NIN [92].…”

Section: Hna-4mentioning

confidence: 99%

Molecular Genetics of the Human Neutrophil Antigens

Flesch

Reil²

2018

Transfus Med Hemother

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Background and Objective: Antibodies to human neutrophil antigens (HNAs) have been implicated in transfusion-related acute lung injury and allo- and autoimmune neutropenia. To date, five HNA systems are assigned, and during the last decades enormous efforts have been undertaken to identify the underlying genes and to characterize the antigens. This review of the literature will provide the current genetic, molecular and functional information on HNAs. Recent Findings: New information on alleles and antigens has been added to nearly each of the five HNA systems. HNA-1d has been added as the antithetical epitope to HNA-1c that is located on the glycoprotein encoded by FCGR3B*02 but not by FCGR3B. FCGR3B*04 and *05 now are included as new alleles. A CD177*787A>T substitution was demonstrated as the main reason for the HNA-2-negative phenotype on neutrophils. The target glycoprotein of HNA-3 antibodies could be identified as choline transporter-like protein 2 (CTL2) encoded by SLC44A2. The conformation sensitive epitope discriminates between arginine and glutamine at position 152 resulting in HNA-3a and HNA-3b. An additional Leu151Phe substitution can impair HNA-3a antibody binding. Recently an alloantibody against HNA-4b which discriminates from HNA-4a by an Arg61His exchange of the glycoprotein encoded by the ITGAM gene was reported in neonatal alloimmune neutropenia. An update of the current HNA nomenclature based on the new findings was provided in 2016 by the ISBT Granulocyte Immunobiology Working Party nomenclature subcommittee. Conclusions: The molecular basis of each of the five HNA antigen systems has been decoded during the past decades. This enables reliable molecular typing strategies, antibody detection and specification as well as development of new assays based on recombinant antigens. However, research on HNA alleles, antigens, and antibodies is not finally terminated and also in the future will add new findings.

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Section: Hna-4mentioning

confidence: 99%

Molecular Genetics of the Human Neutrophil Antigens

Flesch

Reil²

2018

Transfus Med Hemother

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“…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.…”

Section: Pathologymentioning

confidence: 99%

Neonatal Alloimmune Neutropenia

Porcelijn

Haas

2018

Transfus Med Hemother

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Neonatal alloimmune neutropenia (NAIN, NAIN or NIN) is a neutrophil blood group antagonism, analogous to hemolytic disease of the fetus and newborn (HDFN) and fetal/neonatal alloimmune thrombocytopenia (FNAIT). A limited number of prospective screening studies showed that granulocyte-specific antibodies were detectable in 0.35-1.1% of random postnatal maternal samples and that the incidence of NAIN was below 0.1%. Symptoms vary from none to mild skin infections, omphalitis or more severe infections like pneumonia, sepsis, and meningitis. Treatment of neonatal infection with antibiotics and granulocyte-colony stimulating factor is advised.

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“…The GIFT and GAT were performed as previously described (Fung et al, 2003). In the GIFT, cultured cells were fixed with 1% paraformaldehyde, washed, and incubated with a positive serum pool.…”

Section: Granulocyte Immunofluorescence Test (Gift) and Granulocyte Amentioning

confidence: 99%

Clinical scale ex vivo manufacture of neutrophils from hematopoietic progenitor cells

Timmins

Palfreyman

Marturana

et al. 2009

Biotech & Bioengineering

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Dose-intensive chemotherapy results in an obligatory period of severe neutropenia during which patients are at high risk of infection. While patient support with donor neutrophils is possible, this option is restricted due to donor availability and logistic complications. To overcome these problems, we explored the possibility of large scale ex vivo manufacture of neutrophils from hematopoietic progenitor cells (HPC). CD34+ HPC isolated from umbilical cord blood (UCB) and mobilized peripheral blood (mPB) were expanded in serum-free medium supplemented with stem cell factor, granulocyte colony stimulating factor, and a thrombopoietin peptide mimetic. After 15 days of cultivation a 5,800-fold expansion in cell number was achieved for UCB, and up to 4,000-fold for mPB, comprising 40% and 60% mature neutrophils respectively. Ex vivo expanded neutrophils exhibited respiratory burst activity similar to that for donor neutrophils, and were capable of killing Candida albicans in vitro. These yields correspond to a more than 10-fold improvement over current methods, and are sufficient for the production of multiple neutrophil transfusion doses per HPC donation. To enable clinical scale manufacture, we adapted our protocol for use in a wave-type bioreactor at a volume of 10 L. This is the first demonstration of a large scale bioprocess suitable for routine manufacture of a mature blood cell product from HPC, and could enable prophylactic neutrophil support for chemotherapy patients.

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Alloimmune neonatal neutropenia linked to anti‐HNA‐4a

Cited by 41 publications

References 20 publications

Molecular Genetics of the Human Neutrophil Antigens

Molecular Genetics of the Human Neutrophil Antigens

Neonatal Alloimmune Neutropenia

Clinical scale ex vivo manufacture of neutrophils from hematopoietic progenitor cells

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