Developments in the definition and clinical impact of human neutrophil antigens

Muschter, Stefan; Berthold, T.; Greinacher, Andreas

doi:10.1097/moh.0b013e32834babdd

Cited by 38 publications

(42 citation statements)

References 69 publications

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“…CTL2 is a 68-72 kDa transmembrane protein characterized by ten hydrophobic membrane-spanning domains, five extracellular loops, and six intracellular regions with one predicted and two confirmed N-linked glycosylation sites and potential disulfide bonds (fig. 5) [19,75]. This special conformation aggravates the development of assays for the detection of HNA-3 antibodies based on recombinant CTL2 protein because the posttranslational modifications of the protein and the correct conformation within the neutrophil membrane are required for antibody binding [77,78,79,80].…”

Section: Hna-3mentioning

confidence: 99%

“…The HNA-4a allele frequencies in most populations have been determined with about 0.9-1.0 [84,90,92]. Only Taiwanese and Brazilians have lower frequencies with 0.65-0.92 [19,95]. It is not known whether the function of the CD11b/CD18 complex is influenced by the polymorphism [3].…”

Section: Hna-4mentioning

confidence: 99%

“…However, the high degree of homology between FCGR3B and FCGR3A complicates the development of genotyping assays. With about 1-2 × 10 5 copies per cell the low-affinity IgG1/IgG3 FcγRIIIb mediates clearance of immune complexes and phagocytosis of opsonized microorganisms [17,18,19]. The membrane proximal domain is critical for IgG Fc binding, whereas the function of the HNA-1 epitope carrying distal domain remains unclear [3].…”

Section: Hna-1mentioning

confidence: 99%

“…Upon leukocyte activation the β 2 integrin also is rapidly activated and enables adhesion of the cell to its counter receptors, transmigration, phagocytosis, and oxidative burst [91]. The CD11b/α M subunit is a transmembrane protein with 19 potential and three confirmed N-linked glycosylation sites [19]. It is encoded by the ITGAM gene on chromosome 16p11.2 and codes for a 1,153 amino acid glycoprotein including a 16 amino acid signal peptide which is cleaved in the mature protein (NM_001145808.1, transcript variant 1) [93,94].…”

Section: Hna-4mentioning

confidence: 99%

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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-3mentioning

confidence: 99%

Section: Hna-4mentioning

confidence: 99%

Section: Hna-1mentioning

confidence: 99%

Section: Hna-4mentioning

confidence: 99%

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Molecular Genetics of the Human Neutrophil Antigens

Flesch

Reil²

2018

Transfus Med Hemother

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“…В настоящее время рекомбинантный человеческий Г-КСФ широко используется для стимуляции продук-ции нейтрофилов. Рандомизированное контролируе-мое многоцентровое исследование в рамках Междуна-родного регистра пациентов с тяжелой хронической нейтропенией показало, что введение Г-КСФ для под-держания числа гранулоцитов ≥ 1,0 × 10 9 /л достаточно для обеспечения противоинфекционной защиты для многих пациентов [22]. Режим введения Г-КСФ может быть различным (ежедневно, через день или 3 раза в не-делю).…”

Section: клинические проявленияunclassified