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Multicenter Study on Differential Human Neutrophil Antigen 2 Expression and Underlying Molecular Mechanisms.

ABSTRACT: 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-2_null 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 CD177^pos. and a CD177^neg. 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-2_null 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% CD177^pos. neutrophils carried the *787A wild-type allele, whereas a lower rate of CD177^pos. 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 CD177^pos. and CD177^neg. 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.

SUBMITTER: Flesch BK

PROVIDER: S-EPMC7590758 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Multicenter Study on Differential Human Neutrophil Antigen 2 Expression and Underlying Molecular Mechanisms.

Flesch Brigitte K BK Reil Angelika A Nogués Núria N Canals Carme C Bugert Peter P Schulze Torsten J TJ Huiskes Elly E Porcelijn Leendert L Höglund Petter P Ratcliffe Paul P Schönbacher Marlies M Kerchrom Hans H Kellershohn Josina J Bayat Behnaz B

Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie 20200122 5

<h4>Background</h4>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-2<sub>null</sub> 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 CD177<sup>pos.</sup> and a CD177<sup>neg.</sup> subpopulation. The molecular backgroun ...[more]

PMID: 33173457

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Project description:Fever implies a significant increase in corporal temperature that aids toward the resolution of infective processes such as viral disease. The majority of vertebrate species are not homeothermic therefore must rely upon the environment for temperature regulation. Here we show that in the zebrafish an artificial viral infection, induced by poly (I:C), induces a fever response regulated by the behavioral choice of temperature. We recorded 12 h of the diurnal cycle in zebrafish previously treated (first 12 hours dark cycle) with the pyrogen, poly (I:C) [10 μg⋅kg-1]. Fish, n=10, were held in a thermal gradient (36-180C) separated into 7 interconnected chambers. Presence or absence of individuals in each chamber was recorded each 15 minutes throughout the 12 hour period. After the experimental period we dissected whole brains for microarray analysis. In monitored zebrafish intraperitoneal treatment with poly (I:C) induced a febrile behaviour with significantly elevated temperature preference (T of about 32ºC) in stark contrast with the observed frequency for saline-injected fish (28ºC). Microarray analyses uncovered significant shifts in transcriptional activity that were highly directed in the poly (I:C)-treated fish housed in the thermal gradient. When compared to gene expression profiles from poly (I:C)-treated fish deprived of a thermal gradient we observed a less intense specific to the poly (I:C) challenge and interestingly observed a scattered generalised stress response. Our results highlight the influence of temperature preference in the development of the immune response in zebrafish. Fever induced gene expression in zebrafish brain was measured at 24 after intra peritoneal injection with 1mg*Kg-1 of Poly (I:C) in zebrafish. Four independent experiments were performed to explore the transcriptomic profile induced by animals injected by Poly (I:C) with/whithout thermal gradient, saline solution (PBS), or control using different animals for each experiment.

Dataset Information

Multicenter Study on Differential Human Neutrophil Antigen 2 Expression and Underlying Molecular Mechanisms.

Publications

Multicenter Study on Differential Human Neutrophil Antigen 2 Expression and Underlying Molecular Mechanisms.

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