Association of early life anti-pathogen immune responses with infant food sensitisation and allergy: An elastic-net stability-selection approach.

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.