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Untargeted breathomics identifies metabolic signatures of immune activity, intestinal integrity, and fatigue in systemic lupus erythematosus

2026/01/02 by Ioannis Parodis, Martina Iacubino, Lorenzo Rocco +15 · 1 citation
Engineering · Nursing · Medicine · #Advanced Chemical Sensor Technologies #Biochemical Analysis and Sensing Techniques #Systemic Lupus Erythematosus Research

paper · pdf · doi:10.1016/j.ard.2025.12.005

Abstract

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with pronounced clinical heterogeneity and symptom burden. Despite growing knowledge of SLE biology, sensitive noninvasive biomarkers for monitoring disease activity remain lacking. This study aimed to characterise the breath metabolome in SLE and to explore associations between volatile organic compounds (VOCs) and clinical features, including disease activity and fatigue. METHODS: Exhaled breath was collected from 30 SLE patients and 30 matched healthy controls using the ReCIVA Breath Sampler and analysed by thermal desorption gas chromatography-mass spectrometry. VOCs were identified using high-resolution libraries and classified by confidence levels. Associations with clinical and patient-reported outcomes were evaluated, including disease activity indices, fatigue scores, Definition Of Remission In SLE remission, and Lupus Low Disease Activity State. RESULTS: Of 1433 detected VOCs, 539 exhibited levels over background and were considered breath-derived. Distinct breathomic signatures discriminated patients from controls and stratified patients by SLE activity and fatigue burden. Five VOC clusters were identified. Methyl acetate was inversely associated with disease activity and fatigue, suggesting a role in immune homeostasis. A cluster of branched alkenes and alcohols was associated with active disease and greater fatigue, aligning with oxidative stress and lipid peroxidation. Nitrogen-containing heterocycles displayed U-shaped patterns across disease states, potentially reflecting varying intestinal permeability. CONCLUSIONS: This is the first study to characterise the breath metabolome in SLE. VOC signatures reflected immunometabolic perturbations, oxidative stress, and gut barrier integrity. Breathomics may provide a noninvasive means to monitor disease activity and symptom burden in SLE.

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