Association of early life anti-pathogen immune responses with infant food sensitisation and allergy: An elastic-net stability-selection approach.
4 affiliations
- 1Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
- 2Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
- 3Immunology, Vaccinology, Rheumatology and Infectious Diseases Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
- 4Department of Infectious Diseases, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
Abstract
Background
The development of food sensitisation (FS) and food allergy (FA) reflects complex interactions between genetic, environmental and immunological factors, which conventional univariate approaches may fail to capture. This exploratory study applied penalised regression to determine whether early-life immune responses to common pathogens are associated with infant FS and FA.Methods
At 1 year of age, FS was determined by skin prick test and FA by allergy/tolerance history and oral food challenge. Elastic net regression (ENR) was applied to cytokine response data (13 cytokines) from whole blood stimulation (11 microbial stimuli) collected at 6 months of age (n = 147), together with longitudinal clinical data from MIS BAIR trial infants. Stably selected variables (0.75) were analysed by multivariable logistic regression to explore the direction of association of the stably selected variables.Results
For FS, 13 cytokine-stimulant pairs were stably selected in cytokine-only ENR models. After including early-life clinical factors, four pairs were retained. Two were inversely associated with FS (Haemophilus influenzae IL-1Ra and Pam3CSK4 MIP-1α). Two were positively associated (Streptococcus pyogenes IL-1Ra and peptidoglycan IFN-γ). For FA, four cytokine-stimulant pairs were selected in cytokine-only ENR models. Two were positively associated with FA (Escherichia coli-stimulated MCP-1 and S. pyogenes IP-10), and two inversely associated (Pam3CSK4 IL-1Ra and H. influenzae IL-1Ra). No cytokine responses were selected after inclusion of clinical factors in the FA model. The most consistently selected clinical factors were infant eczema for FS and topical corticosteroid treatment by 6 months for FA likely due to disease severity.Conclusion
Early-life cytokine responses to pathogens associated with FS and FA at 1 year were identified through stability selection. While hypothesis-generating, findings were consistent with a role for early immune perturbation in the development of food sensitisation.
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BibTeX
@article{mcdonald2026association,
title = {{Association of early life anti-pathogen immune responses with infant food sensitisation and allergy: An elastic-net stability-selection approach.}},
author = {Ellie McDonald and Sofie Biering-Sørensen and Laure F Pittet and Nigel Curtis and Nicole L Messina},
journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology},
year = {2026},
month = oct,
doi = {10.1111/pai.70513},
url = {https://europepmc.org/article/MED/42910596},
note = {CC BY},
}
RIS
TY - JOUR
TI - Association of early life anti-pathogen immune responses with infant food sensitisation and allergy: An elastic-net stability-selection approach.
AU - Ellie McDonald
AU - Sofie Biering-Sørensen
AU - Laure F Pittet
AU - Nigel Curtis
AU - Nicole L Messina
PY - 2026
DA - 2026/10/01
JO - Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
DO - 10.1111/pai.70513
UR - https://europepmc.org/article/MED/42910596
AB - Background The development of food sensitisation (FS) and food allergy (FA) reflects complex interactions between genetic, environmental and immunological factors, which conventional univariate approaches may fail to capture. This exploratory study applied penalised regression to determine whether early-life immune responses to common pathogens are associated with infant FS and FA.Methods At 1 year of age, FS was determined by skin prick test and FA by allergy/tolerance history and oral food challenge. Elastic net regression (ENR) was applied to cytokine response data (13 cytokines) from whole blood stimulation (11 microbial stimuli) collected at 6 months of age (n = 147), together with longitudinal clinical data from MIS BAIR trial infants. Stably selected variables (0.75) were analysed by multivariable logistic regression to explore the direction of association of the stably selected variables.Results For FS, 13 cytokine-stimulant pairs were stably selected in cytokine-only ENR models. After including early-life clinical factors, four pairs were retained. Two were inversely associated with FS (Haemophilus influenzae IL-1Ra and Pam3CSK4 MIP-1α). Two were positively associated (Streptococcus pyogenes IL-1Ra and peptidoglycan IFN-γ). For FA, four cytokine-stimulant pairs were selected in cytokine-only ENR models. Two were positively associated with FA (Escherichia coli-stimulated MCP-1 and S. pyogenes IP-10), and two inversely associated (Pam3CSK4 IL-1Ra and H. influenzae IL-1Ra). No cytokine responses were selected after inclusion of clinical factors in the FA model. The most consistently selected clinical factors were infant eczema for FS and topical corticosteroid treatment by 6 months for FA likely due to disease severity.Conclusion Early-life cytokine responses to pathogens associated with FS and FA at 1 year were identified through stability selection. While hypothesis-generating, findings were consistent with a role for early immune perturbation in the development of food sensitisation.
SN - 0905-6157
SN - 1399-3038
ER -