What question did this study set out to answer?

To identify serum biomarkers associated with oxidative stress and metabolic changes in β-thalassemia.

March 7, 2026Open Access

Serum Metabolomic Signatures Indicate Oxidative Membrane Lipid Remodeling in β-Thalassemia

Key Points

To identify serum biomarkers associated with oxidative stress and metabolic changes in β-thalassemia.
Used untargeted metabolomics profiling in serum samples from adults with β-thalassemia and healthy controls.
Applied UHPLC-Orbitrap MS for metabolite detection.
Employed multivariate modeling and univariate statistics for data analysis.
Conducted pathway enrichment analysis to identify metabolic processes.
Detected 183 metabolites, with 124 decreased and 54 increased in β-thalassemia patients compared to controls.
Key discriminants included specific lysophosphatidylcholines and conjugated bile acids.
Significant enrichment of pathways involved in linoleic acid and arachidonic acid metabolism.
No significant metabolic differences were observed between transfusion-dependent and non-transfusion-dependent patients.

Abstract

Background/Objectives: Oxidative stress and iron overload remodel erythrocyte membranes in β-thalassemia, but their systemic metabolic correlates are not well defined. We applied untargeted metabolomics to identify serum biomarkers reflecting these pathophysiological processes. Methods: Thirty-one adults with β-thalassemia 18 transfusion-dependent (TDT), 13 non-transfusion-dependent (NTD) and 8 age/sex-matched healthy controls were studied. Fasting serum was profiled using untargeted UHPLC–Orbitrap MS. Multivariate modeling (SIMCA-P) and FDR-controlled univariate statistics identified discriminant features, followed by pathway enrichment analysis. Associations with clinical variables (chelation regimen, ferritin, cardiac MRI T2*, and liver iron concentration) were examined. Results: A total of 183 metabolites were detected; versus controls, 124 were decreased, 54 increased, and 5 remained unchanged in patients. Key discriminants included lysophosphatidylcholines (LysoPC 18:1, 18:3), polyunsaturated fatty acid (PUFA)-bearing phosphatidylcholines (PC 20:4/18:0, PC 18:0/20:4), conjugated bile acids (glycocholic acid, glycochenodeoxycholic acid, and glycoursodeoxycholic acid), and bilirubin. Pathway analysis revealed significant enrichment (FDR-corrected) in linoleic acid metabolism (q = 0.024, impact = 1.000) and arachidonic acid metabolism (q = 0.022, impact = 0.433), with supportive nominal signals from glycerophospholipid (impact = 0.401) and porphyrin/heme (impact = 0.242) pathways. No significant metabolic differences were observed between TD and NTD patients. Conclusions: β-thalassemia serum metabolomics reflects oxidative membrane lipid remodeling with a prominent PLA2/LysoPC–arachidonic axis and evidence of heme turnover and altered bile-acid signaling. These data propose a practical biomarker panel-LysoPCs, arachidonic acid-enriched PCs, and conjugated bile acids-warranting targeted validation alongside conventional clinical parameters for disease monitoring and therapeutic assessment.

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Cite This Study

Makis et al. (Thu,) studied this question.

synapsesocial.com/papers/69abc1845af8044f7a4ea4a6 https://doi.org/https://doi.org/10.3390/metabo16030170

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