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在人类急性过敏反应期间,参与血小板聚集和激活的基因表达下调。

Genes involved in platelet aggregation and activation are downregulated during acute anaphylaxis in humans.

作者信息

McGrath Francesca M, Francis Abbie, Fatovich Daniel M, Macdonald Stephen Pj, Arendts Glenn, Woo Andrew J, Bosio Erika

机构信息

Centre for Clinical Research in Emergency Medicine Harry Perkins Institute of Medical Research Perth WA Australia.

Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia Nedlands WA Australia.

出版信息

Clin Transl Immunology. 2022 Dec 26;11(12):e1435. doi: 10.1002/cti2.1435. eCollection 2022.

Abstract

OBJECTIVE

Mechanisms underlying the anaphylactic reaction in humans are not fully understood. Here, we aimed at improving our understanding of anaphylaxis by investigating gene expression changes.

METHODS

Microarray data set GSE69063 was analysed, describing emergency department (ED) patients with severe anaphylaxis ( = 12), moderate anaphylaxis ( = 6), sepsis ( = 20) and trauma ( = 11). Samples were taken at ED presentation (T0) and 1 h later (T1). Healthy controls were age and sex matched to ED patient groups. Gene expression changes were determined using , and pathway analysis applied. Differentially expressed genes were validated in an independent cohort of anaphylaxis patients ( = 31) and matched healthy controls ( = 10), using quantitative reverse transcription-polymerase chain reaction.

RESULTS

Platelet aggregation was dysregulated in severe anaphylaxis at T0, but not in moderate anaphylaxis, sepsis or trauma. Dysregulation was not observed in patients who received adrenaline before T0. Seven genes ( (adjusted value = 5.57 × 10), (adjusted value = 9.40 × 10), (adjusted -value = 2.15 × 10), (adjusted -value = 2.29 × 10), (adjusted -value = 1.20 × 10), (adjusted -value = 1.39 × 10) and (adjusted -value = 4.06 × 10)) were significantly downregulated in severe anaphylaxis patients who did not receive adrenaline before ED arrival, compared with healthy controls. One gene ( (adjusted -value = 1.29 × 10)) was significantly downregulated in moderate anaphylaxis patients who did not receive adrenaline before ED arrival, compared with healthy controls.

CONCLUSION

Downregulation of genes involved in platelet aggregation and activation is a unique feature of the early anaphylactic reaction not previously reported and may be associated with reaction severity.

摘要

目的

人类过敏反应的潜在机制尚未完全明确。在此,我们旨在通过研究基因表达变化来增进对过敏反应的理解。

方法

分析了基因芯片数据集GSE69063,该数据集描述了急诊科(ED)患有严重过敏反应(n = 12)、中度过敏反应(n = 6)、脓毒症(n = 20)和创伤(n = 11)的患者。在患者到达急诊科时(T0)和1小时后(T1)采集样本。健康对照在年龄和性别上与急诊科患者组相匹配。使用[具体方法未给出]确定基因表达变化,并进行通路分析。在一个独立的过敏反应患者队列(n = 31)和匹配的健康对照(n = 10)中,采用定量逆转录 - 聚合酶链反应对差异表达基因进行验证。

结果

在T0时,严重过敏反应患者的血小板聚集失调,但中度过敏反应、脓毒症或创伤患者未出现这种情况。在T0前接受肾上腺素治疗的患者中未观察到失调。与健康对照相比,7个基因([基因名称未给出,调整后p值 = 5.57×10][多个基因及对应调整后p值均未给出])在到达急诊科前未接受肾上腺素治疗的严重过敏反应患者中显著下调。与健康对照相比,1个基因([基因名称未给出,调整后p值 = 1.29×10])在到达急诊科前未接受肾上腺素治疗的中度过敏反应患者中显著下调。

结论

参与血小板聚集和激活的基因下调是早期过敏反应的一个独特特征,此前未见报道,且可能与反应严重程度相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d34d/9791329/76f0cdd6f85a/CTI2-11-e1435-g004.jpg

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