Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet’s disease
Abstract Background Behçet’s disease (BD) is a systemic inflammatory disease that involves various organs. The clinical manifestation-based diagnosis of BD is a time-consuming process, which makes it difficult to distinguish from patients with similar symptoms. Moreover, an authentic biomarker has n...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-022-02986-5 |
| _version_ | 1797958534297550848 |
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| author | Soo Jin Park Mi Jin Park Sun Park Eun-So Lee Do Yup Lee |
| author_facet | Soo Jin Park Mi Jin Park Sun Park Eun-So Lee Do Yup Lee |
| author_sort | Soo Jin Park |
| collection | DOAJ |
| description | Abstract Background Behçet’s disease (BD) is a systemic inflammatory disease that involves various organs. The clinical manifestation-based diagnosis of BD is a time-consuming process, which makes it difficult to distinguish from patients with similar symptoms. Moreover, an authentic biomarker has not been developed for accurate diagnosis yet. Our current study investigated the unique metabolic signatures of BD and explored biomarkers for precise diagnosis based on an untargeted metabolomic approach. Methods Integrative metabolomic and lipidomic profiling was performed on plasma samples of BD patients (n = 40), healthy controls (HCs, n = 18), and disease controls (DCs, n = 17) using GC-TOF MS and LC-Orbitrap MS. Additionally, the lipid profiles of 66 peripheral blood mononuclear cells (PBMCs) were analyzed from 29 BD patients, 18 HCs, and 19 DCs. Results Plasma metabolic dysfunction in BD was determined in carbohydrate, hydroxy fatty acid, and polyunsaturated fatty acid metabolisms. A plasma biomarker panel with 13 compounds was constructed, which simultaneously distinguished BD from HC and DC (AUCs ranged from 0.810 to 0.966). Dysregulated PBMC metabolome was signatured by a significant elevation in lysophosphatidylcholines (LPCs) and ether-linked lysophosphatidylethanolamines (EtherLPEs). Ten PBMC-derived lipid composites showed good discrimination power (AUCs ranged from 0.900 to 0.973). Correlation analysis revealed a potential association between disease activity and the metabolites of plasma and PBMC, including sphingosine-1 phosphate and EtherLPE 18:2. Conclusions We identified metabolic biomarkers from plasma PBMC, which selectively discriminated BD from healthy control and patients with similar symptoms (recurrent mouth ulcers with/without genital ulcers). The strong correlation was determined between the BD activity and the lipid molecules. These findings may lead to the development for diagnostic and prognostic biomarkers based on a better understanding of the BD pathomechanism. |
| first_indexed | 2024-04-11T00:20:23Z |
| format | Article |
| id | doaj.art-0bbf52766b604b9f82dc7c1dec0a5baf |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-11T00:20:23Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-0bbf52766b604b9f82dc7c1dec0a5baf2023-01-08T12:17:33ZengBMCArthritis Research & Therapy1478-63622023-01-0125111310.1186/s13075-022-02986-5Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet’s diseaseSoo Jin Park0Mi Jin Park1Sun Park2Eun-So Lee3Do Yup Lee4Department of Agricultural Biotechnology, Seoul National UniversityDepartment of Dermatology, Ajou University School of MedicineDepartment of Microbiology, Ajou University School of MedicineDepartment of Dermatology, Ajou University School of MedicineDepartment of Agricultural Biotechnology, Seoul National UniversityAbstract Background Behçet’s disease (BD) is a systemic inflammatory disease that involves various organs. The clinical manifestation-based diagnosis of BD is a time-consuming process, which makes it difficult to distinguish from patients with similar symptoms. Moreover, an authentic biomarker has not been developed for accurate diagnosis yet. Our current study investigated the unique metabolic signatures of BD and explored biomarkers for precise diagnosis based on an untargeted metabolomic approach. Methods Integrative metabolomic and lipidomic profiling was performed on plasma samples of BD patients (n = 40), healthy controls (HCs, n = 18), and disease controls (DCs, n = 17) using GC-TOF MS and LC-Orbitrap MS. Additionally, the lipid profiles of 66 peripheral blood mononuclear cells (PBMCs) were analyzed from 29 BD patients, 18 HCs, and 19 DCs. Results Plasma metabolic dysfunction in BD was determined in carbohydrate, hydroxy fatty acid, and polyunsaturated fatty acid metabolisms. A plasma biomarker panel with 13 compounds was constructed, which simultaneously distinguished BD from HC and DC (AUCs ranged from 0.810 to 0.966). Dysregulated PBMC metabolome was signatured by a significant elevation in lysophosphatidylcholines (LPCs) and ether-linked lysophosphatidylethanolamines (EtherLPEs). Ten PBMC-derived lipid composites showed good discrimination power (AUCs ranged from 0.900 to 0.973). Correlation analysis revealed a potential association between disease activity and the metabolites of plasma and PBMC, including sphingosine-1 phosphate and EtherLPE 18:2. Conclusions We identified metabolic biomarkers from plasma PBMC, which selectively discriminated BD from healthy control and patients with similar symptoms (recurrent mouth ulcers with/without genital ulcers). The strong correlation was determined between the BD activity and the lipid molecules. These findings may lead to the development for diagnostic and prognostic biomarkers based on a better understanding of the BD pathomechanism.https://doi.org/10.1186/s13075-022-02986-5MetabolomicsLipidomicsBehçet’s diseaseAutoimmune disease |
| spellingShingle | Soo Jin Park Mi Jin Park Sun Park Eun-So Lee Do Yup Lee Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet’s disease Arthritis Research & Therapy Metabolomics Lipidomics Behçet’s disease Autoimmune disease |
| title | Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet’s disease |
| title_full | Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet’s disease |
| title_fullStr | Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet’s disease |
| title_full_unstemmed | Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet’s disease |
| title_short | Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet’s disease |
| title_sort | integrative metabolomics of plasma and pbmcs identifies distinctive metabolic signatures in behcet s disease |
| topic | Metabolomics Lipidomics Behçet’s disease Autoimmune disease |
| url | https://doi.org/10.1186/s13075-022-02986-5 |
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