Abbie Francis1,2, Erika Bosio3,4, Shelley F Stone3,4, Daniel M Fatovich3,4,5, Glenn Arendts3,4,5,6, Stephen P J MacDonald3,4,5,7, Sally Burrows8, Simon G A Brown3,4,5,9. 1. Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Washington, Australiaabbie.francis@uwa.edu.au. 2. Division of Emergency Medicine, Medical School, University of Western Australia, Perth, Washington, Australiaabbie.francis@uwa.edu.au. 3. Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Washington, Australia. 4. Division of Emergency Medicine, Medical School, University of Western Australia, Perth, Washington, Australia. 5. Emergency Department, Royal Perth Hospital, Perth, Washington, Australia. 6. Emergency Department, Fiona Stanley Hospital, Murdoch, Washington, Australia. 7. Emergency Department, Armadale-Kelmscott Memorial Hospital, Mount Nasura, Washington, Australia. 8. School of Medicine and Pharmacology, University of Western Australia, Perth, Washington, Australia. 9. Emergency Department, Royal Hobart Hospital, Hobart, Tasmania, Australia.
Abstract
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.
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.
Authors: Khui Hung Lee; Anthony Bosco; Michael O'Sullivan; Yong Song; Jessica Metcalfe; Kan Yu; Benjamin J Mullins; Richard Loh; Guicheng Zhang Journal: World Allergy Organ J Date: 2022-02-10 Impact factor: 4.084
Authors: Lauren M Buelow; Akihiko Hoji; Kiet Tat; Lindsay M Schroeder-Carter; Daniela J Carroll; Joan M Cook-Mills Journal: Front Allergy Date: 2021-09-06
Authors: Jan J M Cuppen; Cristian Gradinaru; Bregje E Raap-van Sleuwen; Anna C E de Wit; Ton A A J van der Vegt; Huub F J Savelkoul Journal: Bioelectromagnetics Date: 2022-04-28 Impact factor: 1.848