Genomic Responses during Acute Human Anaphylaxis Are Characterized by Upregulation of Innate Inflammatory Gene Networks

Stone, Shelley F.; Bosco, Anthony; Jones, Anya C.; Cotterell, Claire L.; Eeden, Pauline E. van; Arendts, Glenn; Fatovich, Daniel M; Brown, Simon G A

doi:10.1371/journal.pone.0101409

Cited by 22 publications

(46 citation statements)

References 61 publications

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“…The cytokine results validate the microarray analysis and support previously reported findings in a different cohort of anaphylaxis patients [7, 19]. The increases observed in these cytokines during anaphylaxis highlight the involvement of innate immune cell activation.…”

Section: Discussionsupporting

confidence: 90%

“…As a validation of results of a previous microarray investigation by our group [7], this study provides evidence of association with anaphylaxis in nearly all of the selected mRNA and/or protein targets. Taken together, the results provide support for the hypothesis that innate immune pathways and myeloid cells such as neutrophils are activated during human anaphylaxis.…”

Section: Discussionsupporting

confidence: 80%

“…A previous microarray study performed in our laboratory aimed to investigate differential gene expression during the course of anaphylaxis [7]. This study investigated 6 patients with moderate anaphylaxis who were sampled over the first 3 hours after arrival at the emergency department.…”

Section: Introductionmentioning

confidence: 99%

“…An increasing number of genes were differentially expressed over this time, culminating in a storm of genetic activation. Several key pathways including inflammation, innate immunity, apoptosis, neutrophil activation, and chemotaxis were upregulated, suggesting these pathways play central roles in the anaphylactic response [7]. The present study aimed to investigate some of these processes more closely during anaphylaxis by analyzing the mRNA expression of some important genes in peripheral blood leucocytes and their corresponding protein levels in serum/plasma, where possible.…”

Section: Introductionmentioning

confidence: 99%

“…The selected targets were identified in our previous microarray study [7] as either “hub genes” or upstream regulators for the pathways of interest including: interleukin (IL)-6; IL-10; oncostatin M (OSM); S100 calcium-binding proteins A8 (S100A8) and A9 (S100A9); matrix metalloproteinase 9 (MMP9); Fas ligand (FasL); toll-like receptor 4 (TLR4); myeloid differentiation primary response 88 (MyD88); triggering receptor expressed on myeloid cells 1 (TREM1); and cluster of differentiation 64 (CD64). IL-6, IL-10, and OSM are cytokines that play important roles in innate immunity by performing either pro- or anti-inflammatory functions [8, 9].…”

Section: Introductionmentioning

confidence: 99%

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Markers Involved in Innate Immunity and Neutrophil Activation are Elevated during Acute Human Anaphylaxis: Validation of a Microarray Study

Francis¹,

Bosio²,

Stone³

et al. 2018

J Innate Immun

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Background: We have previously identified the upregulation of the innate immune response, neutrophil activation, and apoptosis during anaphylaxis using a microarray approach. This study aimed to validate the differential gene expression and investigate protein concentrations of “hub genes” and upstream regulators during anaphylaxis. Methods: Samples were collected from patients with anaphylaxis on their arrival at the emergency department, and after 1 and 3 h. mRNA levels of 11 genes (interleukin-6 [IL-6], IL-10, oncostatin M [OSM], S100A8, S100A9, matrix metalloproteinase 9 [MMP9], FASL, toll-like receptor 4 [TLR4], MYD88, triggering receptor expressed on myeloid cells 1 [TREM1], and cluster of differentiation 64 [CD64]) were measured in peripheral blood leucocytes using qPCR. Serum protein concentrations were measured by ELISA or cytometric bead array for 6 of these candidates. Results: Of 69 anaphylaxis patients enrolled, 36 (52%) had severe reactions, and 38 (55%) were female. Increases in both mRNA and protein of IL-10, S100A9, MMP9, and TREM1 were observed. OSM, S100A8, TLR4, and CD64 were upregulated and IL-6 protein concentrations were increased during anaphylaxis. Both FASL and soluble Fas ligand decreased during anaphylaxis. Conclusion: These results provide evidence for the involvement of innate immune pathways and myeloid cells during human anaphylaxis, validating previous microarray findings. Elevated S100A8, S100A9, TLR4, and TREM1 expression, and increased S100A9 and soluble TREM1 protein concentrations strongly suggest that neutrophils are activated during acute anaphylaxis.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Markers Involved in Innate Immunity and Neutrophil Activation are Elevated during Acute Human Anaphylaxis: Validation of a Microarray Study

Francis¹,

Bosio²,

Stone³

et al. 2018

J Innate Immun

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

et al. 2022

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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 (n = 12), moderate anaphylaxis (n = 6), sepsis (n = 20) and trauma (n = 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 limma, and pathway analysis applied. Differentially expressed genes were validated in an independent cohort of anaphylaxis patients (n = 31) and matched healthy controls (n = 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 (GATA1 (adjusted P-value = 5.57 9 10 À4 ), TLN1 (adjusted P-value = 9.40 9 10 À4 ), GP1BA (adjusted P-value = 2.15 9 10 À2 ), SELP (adjusted P-value = 2.29 9 10 À2 ), MPL (adjusted P-value = 1.20 9 10 À2 ), F13A1 (adjusted P-value = 1.39 9 10 À2 ) and SPARC (adjusted P-value = 4.06 9 10 À2 )) were significantly downregulated in severe anaphylaxis patients who did not receive adrenaline before ED arrival, compared with healthy controls. One gene (TLN1 (adjusted P-value = 1.29 9 10 À2 )) 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.

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COMMD8 changes expression during initial phase of wasp venom immunotherapy

Kempinski

Romantowski

Maciejewska

et al. 2020

The Journal of Gene Medicine

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Background: Hymenoptera venom allergy (HVA) is of great concern because of the possibility of anaphylaxis, which may be fatal. Venom immunotherapy (VIT) is the only disease-modifying treatment in HVA and, although efficient, its mechanism remains partially unknown. Gene expression analysis may be helpful for establishing a proper model of tolerance induction during the build-up phase of VIT. The present study aimed to analyze how the start of VIT changes the expression of 15 selected genes. Methods: Forty-five patients starting VIT with a wasp venom allergy were enrolled. The diagnosis was established based on anaphylaxis history (third or fourth grade on the Mueller scale) and positive soluble immunoglobulin E and/or skin tests. Two blood collections were performed in the patient group: before and after 3 months of VIT. One sample was taken in the control group. Gene expression analysis was performed using a reverse transcriptase-polymerase chain reaction with microfluidic cards and normalized to the 18S housekeeping gene. Results: Commd8 was the only gene that changed expression significantly after the start of VIT (p = 0.012). Its expression decreased towards the levels observed in the healthy controls. Twelve out of 15 genes (commd8, cldn1, cngb3, fads1, hes6, hla-drb5, htr3b, prlr, slc16a4, snx33, socs3 and twist2) revealed a significantly different expression compared to the healthy controls. Conclusions: The present study shows that commd8 changes significantly its expression during initial phase of VIT. This gene might be a candidate for VIT biomarker in future studies.

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Genomic Responses during Acute Human Anaphylaxis Are Characterized by Upregulation of Innate Inflammatory Gene Networks

Cited by 22 publications

References 61 publications

Markers Involved in Innate Immunity and Neutrophil Activation are Elevated during Acute Human Anaphylaxis: Validation of a Microarray Study

Markers Involved in Innate Immunity and Neutrophil Activation are Elevated during Acute Human Anaphylaxis: Validation of a Microarray Study

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

COMMD8 changes expression during initial phase of wasp venom immunotherapy

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