Distinct Immunometabolic Profiles in Finnish and Russian Karelian Adolescents With Contrasting Allergy Risk

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.

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.

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.

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.