Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026
Circulating Piwi-Interacting RNAs Associate With Childhood Asthma ICS Response With Vitamin D Effect Modification.
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Li Jiang, Hong Xiaoning, Chi Mengshi, Kho Alvin T, Zhu Zhongxu, Zhang Hui, Liu Tao, McGeachie Michael J, Celedón Juan C, Weiss Scott T, Tantisira Kelan G, Li Jiang
Аннотация
BACKGROUND: Piwi-interacting RNAs (piRNAs) have been linked to type 2-high asthma phenotypes. Although vitamin D modulates inhaled corticosteroid (ICS) response via microRNAs, its potential role through piRNAs remains unknown.
METHODS: Baseline plasma piRNA expression was profiled by small RNA sequencing in 492 participants from the Childhood Asthma Management Program (CAMP), with 187 children randomised to the ICS arm. Serum vitamin D levels were classified as insufficient (≤ 30 ng/mL) or sufficient (> 30 ng/mL). Linear regression was used to assess associations between piRNA expression and changes in prebronchodilator percent predicted forced expiratory volume in 1 s (FEV1%) over 4 years, including interaction analyses with vitamin D status. Replication was performed in 375 ICS-treated participants from the Genetics of Asthma in Costa Rica Study (GACRS).
RESULTS: Fourteen piRNAs were significantly associated with FEV1% changes among vitamin D-insufficient children, six showing significant interactions with vitamin D status (p < 0.05). Four piRNAs were replicated in GACRS, with piR-36241 also confirmed in interaction analyses. Predicted targets of piR-36241 were enriched in immune- and respiratory-related pathways. piR-36241 demonstrated strong predictive performance for ICS response in vitamin D-insufficient children (AUROC = 0.84) and was detected in bronchial epithelial cells, where it was differentially expressed in asthma.
CONCLUSIONS: Circulating piRNAs are associated with ICS response in childhood asthma, with vitamin D acting as an effect modifier, which may serve as non-invasive biomarkers for ICS responsiveness, particularly in vitamin D-insufficient patients.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00000575 and NCT00021840.
METHODS: Baseline plasma piRNA expression was profiled by small RNA sequencing in 492 participants from the Childhood Asthma Management Program (CAMP), with 187 children randomised to the ICS arm. Serum vitamin D levels were classified as insufficient (≤ 30 ng/mL) or sufficient (> 30 ng/mL). Linear regression was used to assess associations between piRNA expression and changes in prebronchodilator percent predicted forced expiratory volume in 1 s (FEV1%) over 4 years, including interaction analyses with vitamin D status. Replication was performed in 375 ICS-treated participants from the Genetics of Asthma in Costa Rica Study (GACRS).
RESULTS: Fourteen piRNAs were significantly associated with FEV1% changes among vitamin D-insufficient children, six showing significant interactions with vitamin D status (p < 0.05). Four piRNAs were replicated in GACRS, with piR-36241 also confirmed in interaction analyses. Predicted targets of piR-36241 were enriched in immune- and respiratory-related pathways. piR-36241 demonstrated strong predictive performance for ICS response in vitamin D-insufficient children (AUROC = 0.84) and was detected in bronchial epithelial cells, where it was differentially expressed in asthma.
CONCLUSIONS: Circulating piRNAs are associated with ICS response in childhood asthma, with vitamin D acting as an effect modifier, which may serve as non-invasive biomarkers for ICS responsiveness, particularly in vitamin D-insufficient patients.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00000575 and NCT00021840.