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. 2023 Nov;13(11):e12308.
doi: 10.1002/clt2.12308.

Inflammatory related plasma proteins involved in acute preschool wheeze

Idun Holmdahl  1   2 , Sandip Chakraborty  1   2 , Angela Hoyer  1   2 , Anastasia Filiou  1   2 , Anna Asarnoj  1   2 , Anders Sjölander  3 , Magnus P Borres  3   4 , Marianne van Hage  5 , Gunilla Hedlin  1 , Jon R Konradsen  1   2 , Cilla Söderhäll  1   2
Affiliations

Inflammatory related plasma proteins involved in acute preschool wheeze

Idun Holmdahl et al. Clin Transl Allergy. 2023 Nov.

Abstract

Background: Preschool wheeze is a risk factor for asthma development. However, the molecular mechanism behind a wheezing episode is not well understood.

Objective: Our aims were to assess the association of plasma proteins with acute preschool wheeze and to study the proteins with differential expression at the acute phase at revisit after 3 months. Additionally, to investigate the relationship between protein expression and clinical parameters.

Method: We measured 92 inflammatory proteins in plasma and clinical parameters from 145 children during an episode of preschool wheeze (PW) and at the revisit after 3 months (PW-R, n = 113/145) and 101 healthy controls (HC) aged 6-48 months in the GEWAC cohort using the antibody-mediated proximity extension-based assay (Olink Proteomics, Uppsala).

Results: Of the 74 analysed proteins, 52 were differentially expressed between PW and HC. The expression profiles of the top 10 proteins, Oncostatin M (OSM), IL-10, IL-6, Fibroblast growth factor 21 (FGF21), AXIN1, CXCL10, SIRT2, TNFSF11, Tumour necrosis factor β (TNF-β) and CASP8, could almost entirely separate PW from HC. Five out of 10 proteins were associated with intake of oral corticosteroids (OCS) 24 h preceding blood sampling (OSM, CASP8, IL-10, TNF-β and CXCL10). No differences in protein expression were seen between PWs with or without OCS in comparison to HC. At the revisit after 3 months, differential protein expressions were still seen between PW-R and HC for three (IL-10, SIRT2 and FGF21) of the 10 proteins.

Conclusion: Our results contribute to unravelling potential immunopathological pathways shared between preschool wheeze and asthma.

Keywords: asthma; inflammation; olink; plasma proteins; preschool wheeze.

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Conflict of interest statement

I.H., A.F., A.H., S.C. and G.H. have no conflict of interest to report. J.R.K. and C.S. have received non‐financial support from Thermo Fisher Scientific. A.A. has received lecture fees from Thermo Fisher Scientific, ALK, Mylan, Semper, Nestlé and Orion Pharma and advisory board fees from Sanofi, Novartis and Aimmune Therapeutics. A.S. and M.P.B. are employees at Thermo Fisher Scientific. M.v.H. reports lecture fees from Thermo Fisher Scientific outside the submitted work.

Figures

FIGURE 1
FIGURE 1
Flow‐chart of number of children with an acute episode of preschool wheeze (PW) and healthy controls (HC) that attended the different follow‐ups and sample collections at each visit. Age in months presented as medians with inter‐quartile ranges (IQR). Comparisons are made between PW at inclusion (during an acute wheezing episode) and HC at inclusion as well as between PW at revisit after 3 months (PW‐R) and HC at inclusion. *113 who left plasma at revisit. CBC, Complete blood count.
FIGURE 2
FIGURE 2
The top 10 most differentially expressed proteins between 145 children with an acute episode of preschool wheeze (PW) and 101 healthy controls (HC). (A) Heat map, plotted with unsupervised clustering, of the top 10 most differentially expressed proteins. (B) Box plot showing protein expression between PW and HC. (C) Fold change and false discovery rate (FDR) of the top 10 most differentially expressed proteins between PW and HC. AXIN 1, Axis inhibition protein 1; CASP8, Caspase 8; CXCL10, C‐X‐C motif chemokine ligand 10; FC, fold change; FDR, false discovery rate; FGF21, Fibroblast Growth Factor 21; HC, healthy controls; IL‐10, Interleukin 10; IL‐6, Interleukin 6; OCS, oral corticosteroids; OSM, Oncostatin M; PW, children with an acute episode of preschool wheeze; SIRT2, Sirtuin 2; TNFβ, Tumor necrosis factor β; TNFSF11, TNF superfamily 11.
FIGURE 3
FIGURE 3
The box plot showing protein expression between children with an acute episode of preschool wheeze (PW) at inclusion, with and without oral corticosteroids (OCS) and healthy controls (HC). Statistical significance between the two groups was calculated using the two‐tailed Mann‐Whitney U test. AXIN1, Axis inhibition protein 1; CASP8, Caspase 8; CXCL10, C‐X‐C motif chemokine ligand 10; FGF21, Fibroblast growth factor 21; IL‐10, Interleukin 10; IL‐6, Interleukin 6; OCS, oral corticosteroids; OSM, Oncostatin M; SIRT2, Sirtuin 2; TNFSF11, TNF superfamily 11; TNFβ, Tumor necrosis factor β.
FIGURE 4
FIGURE 4
(A) Box plot showing protein expression between children with preschool wheeze at revisit after 3 months (PW‐R) and healthy controls (HC) (B) Fold change and false discovery rate (FDR) of PW‐R in comparison to HC. AXIN1, Axis inhibition protein 1; CASP8, Caspase 8; CXCL10, C‐X‐C motif chemokine ligand 10; FC, fold change; FDR, false discovery rate; FGF21, Fibroblast growth factor 21; HC, healthy controls; IL‐10, Interleukin 10; IL‐6, Interleukin 6; OSM, Oncostatin M; PW‐R, children with preschool wheeze at revisit after 3 months; SIRT2, Sirtuin 2; TNFSF11, TNF superfamily 11; TNFβ, Tumor necrosis factor β.
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