Multicenter study on differential human neutrophil antigen 2 expression and underlying molecular mechanisms
Background: The human neutrophil antigen 2 (HNA-2), which is expressed on CD177, is undetectable in 3-5% of the normal population. Exposure of these HNA-2null individuals to HNA-2-positive cells can cause immunization and pro-duction of HNA-2 antibodies, which can induce immune neutropenia and trans...
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| Hauptverfasser: | , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
October 2020
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| In: |
Transfusion medicine and hemotherapy
Year: 2020, Jahrgang: 47, Heft: 5, Pages: 385-395 |
| ISSN: | 1660-3818 |
| DOI: | 10.1159/000505523 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1159/000505523 Verlag, lizenzpflichtig, Volltext: https://karger.com/tmh/article/47/5/385/301659/Multicenter-Study-on-Differential-Human-Neutrophil 
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| Verfasserangaben: | Brigitte K. Flesch, Angelika Reil, Núria Nogués, Carme Canals, Peter Bugert, Torsten J. Schulze, Elly Huiskes, Leendert Porcelijn, Petter Höglund, Paul Ratcliffe, Marlies Schönbacher, Hans Kerchrom, Josina Kellershohn, Behnaz Bayat |
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| 245 | 1 | 0 | |a Multicenter study on differential human neutrophil antigen 2 expression and underlying molecular mechanisms |c Brigitte K. Flesch, Angelika Reil, Núria Nogués, Carme Canals, Peter Bugert, Torsten J. Schulze, Elly Huiskes, Leendert Porcelijn, Petter Höglund, Paul Ratcliffe, Marlies Schönbacher, Hans Kerchrom, Josina Kellershohn, Behnaz Bayat |
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| 520 | |a Background: The human neutrophil antigen 2 (HNA-2), which is expressed on CD177, is undetectable in 3-5% of the normal population. Exposure of these HNA-2null individuals to HNA-2-positive cells can cause immunization and pro-duction of HNA-2 antibodies, which can induce immune neutropenia and transfusion-related acute lung injury. In HNA-2-positive individuals, neutrophils are divided into a CD177pos. and a CD177neg. subpopulation. The molecular background of HNA-2 deficiency and the bimodal expression pattern, however, are not completely decoded. Study Design: An international collaboration was conducted on the genetic analysis of HNA-2-phenotyped blood samples, including HNA-2-deficient individuals, mothers, and the respective children with neonatal immune neutropenia and regular blood donors. Results: From a total of 54 HNA-2null individuals, 43 were homozygous for the CD177*787A>T substitution. Six carried the CD177*c.1291G>A single nucleotide polymorphism. All HNA-2-positive samples with >40% CD177pos. neutrophils carried the *787A wild-type allele, whereas a lower rate of CD177pos. neutrophils was preferentially associated with *c.787AT heterozygosity. Interestingly, only the *c.787A allele sequence was detected in complementary DNA (cDNA) sequence analysis carried out on all *c.787AT heterozygous individuals. However, cDNA analysis after sorting of CD177pos. and CD177neg. neutrophil subsets from HNA-2-positive individuals showed identical sequences, which makes regulatory elements within the promoter unlikely to affect CD177 gene transcription in different CD177 neutrophil subsets. Conclusion: This comprehensive study clearly demonstrates the impact of single nucleotide polymorphisms on the expression of HNA-2 on the neutrophil surface but challenges the hypothesis of regulatory epigenetic effects being implicated in the bimodal CD177 expression pattern. | ||
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