Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026
A circulating odd-chain fatty acid biomarker signature discriminates pediatric allergic rhinitis with asthma from related allergic airway phenotypes.
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Zheng Peiyan, Zhang Yida, Bian Xiqing, Wu Ying, Wang Qing, Chen Junxiong, Jiang Min, Li Na, Sun Baoqing, Wu Jian-Lin
Аннотация
BACKGROUND: Reliable biomarkers for discriminating allergic rhinitis with asthma (ARA) from related allergic airway phenotypes remain lacking in pediatric populations. We aimed to identify and validate circulating metabolic biomarkers of ARA.
METHODS: Serum samples from 380 participants, including healthy controls (HC), allergic rhinitis (AR), asthma (AS), and ARA, underwent untargeted carboxylomics profiling using SPCSDCarboxyl. Candidate biomarkers were evaluated in mouse models and validated in an independent cohort (n = 125) using targeted carboxylomics. Biomarker performance was assessed using multivariate and machine-learning approaches.
RESULTS: ARA was associated with altered circulating odd-chain fatty acids (OCFAs), with valeric, heptanoic, nonanoic, undecanoic, and isovaleric acids showing consistent increased across cohorts. Heptanoic, nonanoic, and undecanoic acids demonstrated excellent discrimination of ARA from HC, with areas under curve (AUC) of 0.96, 0.98, and 0.94, respectively. However, these three OCFAs were broadly elevated across all allergic airway phenotypes and lacked ARA specificity. Least absolute shrinkage and selection operator (LASSO) regression identified valeric and undecanoic acids as complementary discriminatory features for ARA versus AR and AS. Among valeric acid showed the most phenotype-discriminatory performance, with an AUC of 0.72 for ARA versus AR and 0.64 for ARA versus AS. OCFA levels correlated significantly with inflammatory indices and pulmonary function, and comparable alterations were confirmed in mouse models.
CONCLUSIONS: These findings identify a pediatric ARA-specific OCFA signature of a distinct immunometabolic endotype involving propionyl-CoA metabolism and fatty acid oxidation. Valeric acid uniquely discriminated ARA from isolated AR, supporting its potential as a serum reference marker; combination with undecanoic acid or clinical parameters may further improve diagnostic performance.
METHODS: Serum samples from 380 participants, including healthy controls (HC), allergic rhinitis (AR), asthma (AS), and ARA, underwent untargeted carboxylomics profiling using SPCSDCarboxyl. Candidate biomarkers were evaluated in mouse models and validated in an independent cohort (n = 125) using targeted carboxylomics. Biomarker performance was assessed using multivariate and machine-learning approaches.
RESULTS: ARA was associated with altered circulating odd-chain fatty acids (OCFAs), with valeric, heptanoic, nonanoic, undecanoic, and isovaleric acids showing consistent increased across cohorts. Heptanoic, nonanoic, and undecanoic acids demonstrated excellent discrimination of ARA from HC, with areas under curve (AUC) of 0.96, 0.98, and 0.94, respectively. However, these three OCFAs were broadly elevated across all allergic airway phenotypes and lacked ARA specificity. Least absolute shrinkage and selection operator (LASSO) regression identified valeric and undecanoic acids as complementary discriminatory features for ARA versus AR and AS. Among valeric acid showed the most phenotype-discriminatory performance, with an AUC of 0.72 for ARA versus AR and 0.64 for ARA versus AS. OCFA levels correlated significantly with inflammatory indices and pulmonary function, and comparable alterations were confirmed in mouse models.
CONCLUSIONS: These findings identify a pediatric ARA-specific OCFA signature of a distinct immunometabolic endotype involving propionyl-CoA metabolism and fatty acid oxidation. Valeric acid uniquely discriminated ARA from isolated AR, supporting its potential as a serum reference marker; combination with undecanoic acid or clinical parameters may further improve diagnostic performance.