ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Metabolomics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1632244
Untargeted metabolomics reveals the metabolic characteristics and biomarkers of obstetric antiphospholipid syndrome and undifferentiated connective tissue disease
Provisionally accepted- Mianyang Central Hospital, Mianyang, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The clinical differentiation between obstetric antiphospholipid syndrome (OAPS) and undifferentiated connective tissue disease (UCTD) presents significant diagnostic challenges. This study employs metabolomics to investigate metabolic reprogramming patterns in OAPS and UCTD, aiming to identify potential biomarkers for early diagnosis.Using LC-MS-based metabolomics, we analyzed serum profiles from 40 OAPS patients (B1), 30 OAPS+UCTD patients (B2), 27 UCTD patients (B3), and 30 healthy controls (A1). Multivariate PLS-DA modeling, combined with KEGG pathway and Gene Set Enrichment Analysis (GSEA), was applied to identify disease-specific metabolic signatures.Results: Metabolomic profiling detected 1,227 metabolites, including 412 in negative ion mode and 815 in positive ion mode. The two ionization modes exhibited distinct chemical profiles, with PLS-DA analysis demonstrating superior group discrimination in positive ion mode. B1 vs. B2 (Negative ion mode): 9 metabolites were upregulated (notably 17(S)-HpDHA, showing the largest fold-change as a potential biomarker), and 1 metabolite was downregulated (5-sulfosalicylic acid). B1 vs. B2 (Positive ion mode): 17 metabolites were upregulated (including 4-methyl-5-thiazoleethanol, a promising biomarker), and 8 were downregulated. B1 vs. B3 (Negative ion mode): 14 metabolites were upregulated (highlighted by 3-hydroxybenzoic acid, the most significantly altered candidate), and 4 were downregulated. B1 vs. B3 (Positive ion mode): 30 metabolites were upregulated (again featuring 4-methyl-5-thiazoleethanol), and 32 were downregulated. B2 vs. B3 (Negative ion mode): 15 metabolites were upregulated (e.g., chlortetracycline), and 15 were downregulated (notably 6α-prostaglandin I1). B2 vs. B3 (Positive ion mode): 29 metabolites were upregulated (e.g., senecionine), and 64 were downregulated (e.g., SM 9:1 2O/16:4). These metabolites represent robust candidates for group discrimination. Enrichment analysis revealed that distinct metabolic pathways were significantly associated with different groups and ionization modes, suggesting divergent underlying metabolic mechanisms.This study systematically characterizes the metabolic reprogramming in OAPS, UCTD, and their comorbid states, identifying potential diagnostic biomarkers.Differential metabolites and pathway analyses highlight the critical role of immunity, contributing to a theoretical framework for "metabolism-immunity-vascular" interactions.
Keywords: obstetric antiphospholipid syndrome, Undifferentiated connective tissue disease, Metabolomics, untargeted, Metabolic biomarkers
Received: 20 May 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Li, Shi, Shu, Jian, Jinmei and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Siyin Li, Mianyang Central Hospital, Mianyang, China
Jing Yang, Mianyang Central Hospital, Mianyang, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.