Allergy · 2026
Distinct Immunometabolic Profiles in Finnish and Russian Karelian Adolescents With Contrasting Allergy Risk.
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Fyhrquist Nanna, Riskumäki Matilda, Karisola Piia, Nieminen Anni, Laatikainen Tiina, Sinkko Hanna, Paalanen Laura, Jousilahti Pekka, Vartiainen Erkki, Mäkelä Mika J, Haahtela Tari, Alenius Harri
Аннотация
INTRODUCTION: Population differences in allergy prevalence and other immune-mediated disease risk suggest underlying variation in immune and metabolic regulation. It remains poorly understood how these differences are reflected in proteomic profiles and linked to systemic metabolism.
METHODS: We examined Finnish (FIN) and Russian (RUS) adolescents aged 13-21 years from populations with contrasting allergy risk. Protein profiles were measured using the Olink proximity extension assay platform in serum (n = 110). We used unstimulated peripheral blood mononuclear cell (PBMC) supernatants (n = 81) as well as paired PBMC culture supernatants from medium-only control and Acinetobacter lwoffii-stimulated conditions (n = 80 donors). The data were integrated with serum metabolomics, matched PBMC transcriptomics, and allergen-specific IgE. Differential analyses employed age- and sex-adjusted linear models (limma), with false discovery rate control. For metabolite-protein associations, age- and sex-adjusted rank-based partial correlations were used.
RESULTS: The strongest differences were observed in unstimulated PBMC secretomes. FIN participants showed higher basal secretion of inflammatory cytokines and chemokines, including IFN-γ, IL-17A, and CXCL9. This was consistent with a broader low-grade inflammatory PBMC secretory phenotype. RUS participants showed higher levels of a few proteins, including 4E-BP1, CASP-8, and TWEAK. Overall, serum proteomic differences were modest. They involved largely nonoverlapping proteins, indicating that PBMC-derived secretion and serum capture distinct proteomic compartments. Acinetobacter stimulation revealed divergent responses, with stronger induction of selected inflammatory and chemotactic mediators in FIN than in RUS. Metabolite-protein associations were more evident in RUS than in FIN, with taurine-related metabolites positively and cAMP-related signals negatively associated with several serum proteins.
CONCLUSIONS: Together, these findings show that FIN and RUS adolescents with contrasting allergy risk display distinct immunometabolic profiles. FIN adolescents showed a broader pro-inflammatory PBMC secretory phenotype, whereas stronger serum metabolite-protein coupling was observed in RUS adolescents.
METHODS: We examined Finnish (FIN) and Russian (RUS) adolescents aged 13-21 years from populations with contrasting allergy risk. Protein profiles were measured using the Olink proximity extension assay platform in serum (n = 110). We used unstimulated peripheral blood mononuclear cell (PBMC) supernatants (n = 81) as well as paired PBMC culture supernatants from medium-only control and Acinetobacter lwoffii-stimulated conditions (n = 80 donors). The data were integrated with serum metabolomics, matched PBMC transcriptomics, and allergen-specific IgE. Differential analyses employed age- and sex-adjusted linear models (limma), with false discovery rate control. For metabolite-protein associations, age- and sex-adjusted rank-based partial correlations were used.
RESULTS: The strongest differences were observed in unstimulated PBMC secretomes. FIN participants showed higher basal secretion of inflammatory cytokines and chemokines, including IFN-γ, IL-17A, and CXCL9. This was consistent with a broader low-grade inflammatory PBMC secretory phenotype. RUS participants showed higher levels of a few proteins, including 4E-BP1, CASP-8, and TWEAK. Overall, serum proteomic differences were modest. They involved largely nonoverlapping proteins, indicating that PBMC-derived secretion and serum capture distinct proteomic compartments. Acinetobacter stimulation revealed divergent responses, with stronger induction of selected inflammatory and chemotactic mediators in FIN than in RUS. Metabolite-protein associations were more evident in RUS than in FIN, with taurine-related metabolites positively and cAMP-related signals negatively associated with several serum proteins.
CONCLUSIONS: Together, these findings show that FIN and RUS adolescents with contrasting allergy risk display distinct immunometabolic profiles. FIN adolescents showed a broader pro-inflammatory PBMC secretory phenotype, whereas stronger serum metabolite-protein coupling was observed in RUS adolescents.