Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint
Objective: In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) alter their metabolism to support their activation. We aimed to analyse the full spectrum of metabolic alterations associated with RA by performing untargeted metabolomics in RA FLS vs. non-inflamed (NI) FLS. Methods: Untarg...
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2025-12-01
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| Series: | Journal of Translational Autoimmunity |
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| author | Georgios K. Vasileiadis Yuan Zhang Marion Laudette Tahzeeb Fatima Anna-Karin Hultgård Ekwall Reshmi Sureshkumar Ronald van Vollenhoven Jon Lampa Bjorn Gudbjornsson Espen A. Haavardsholm Dan Nordström Gerdur Gröndal Kim Hørslev-Petersen Kristina Lend Merete L. Hetland Michael Nurmohamed Mikkel Østergaard Till Uhlig Tuulikki Sokka-Isler Anna Rudin Jan Borén Monica Guma Cristina Maglio |
| author_facet | Georgios K. Vasileiadis Yuan Zhang Marion Laudette Tahzeeb Fatima Anna-Karin Hultgård Ekwall Reshmi Sureshkumar Ronald van Vollenhoven Jon Lampa Bjorn Gudbjornsson Espen A. Haavardsholm Dan Nordström Gerdur Gröndal Kim Hørslev-Petersen Kristina Lend Merete L. Hetland Michael Nurmohamed Mikkel Østergaard Till Uhlig Tuulikki Sokka-Isler Anna Rudin Jan Borén Monica Guma Cristina Maglio |
| author_sort | Georgios K. Vasileiadis |
| collection | DOAJ |
| description | Objective: In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) alter their metabolism to support their activation. We aimed to analyse the full spectrum of metabolic alterations associated with RA by performing untargeted metabolomics in RA FLS vs. non-inflamed (NI) FLS. Methods: Untargeted annotated metabolomics was performed using mass spectrometry on ten primary RA and seven NI FLS culture extracts and 220 serum samples from participants with early RA from the randomised controlled NORD-STAR trial. Carnitine-related proteins were measured with Western blot. FLS bioenergetic profile was assessed with a Seahorse flux analyser. Results: Metabolomics analysis based on 138 annotated metabolites revealed a distinct metabolic fingerprint between RA and NI FLS. Of the 12 metabolites enriched in RA FLS, 11 were acylcarnitines. Pro-inflammatory stimulation of NI FLS also led to acylcarnitine accumulation. RA FLS exhibited lower levels of CD36, a fatty acid transporter, but similar levels of L-carnitine transporter, and carnitine palmitoyltransferase 1 A and 2 compared to NI FLS. Seahorse analyses showed no difference in fatty acid oxidation between RA and NI FLS; however, RA FLS displayed mitochondrial dysfunction and energetic impairment. Serum acylcarnitine content decreased after 24 weeks of treatment with methotrexate combined with abatacept or tocilizumab in patients with early RA achieving remission. Conclusion: Acylcarnitine accumulation is a characteristic of RA FLS metabolic fingerprint and could be linked to mitochondrial dysfunction. In patients with early RA, acylcarnitine content in serum decreases after successful anti-rheumatic treatment. These results indicate a dysregulation in acylcarnitine metabolism in RA at the joint level and systemically. |
| format | Article |
| id | doaj-art-24e2a9c3ebf94b38bb5706f24de9de42 |
| institution | Kabale University |
| issn | 2589-9090 |
| language | English |
| publishDate | 2025-12-01 |
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| series | Journal of Translational Autoimmunity |
| spelling | doaj-art-24e2a9c3ebf94b38bb5706f24de9de422025-08-23T04:48:55ZengElsevierJournal of Translational Autoimmunity2589-90902025-12-011110031010.1016/j.jtauto.2025.100310Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprintGeorgios K. Vasileiadis0Yuan Zhang1Marion Laudette2Tahzeeb Fatima3Anna-Karin Hultgård Ekwall4Reshmi Sureshkumar5Ronald van Vollenhoven6Jon Lampa7Bjorn Gudbjornsson8Espen A. Haavardsholm9Dan Nordström10Gerdur Gröndal11Kim Hørslev-Petersen12Kristina Lend13Merete L. Hetland14Michael Nurmohamed15Mikkel Østergaard16Till Uhlig17Tuulikki Sokka-Isler18Anna Rudin19Jan Borén20Monica Guma21Cristina Maglio22Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Rheumatology, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Medicine, Rheumatology Unit, Center for Molecular Medicine (CMM), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, Amsterdam, NetherlandsDepartment of Medicine, Rheumatology Unit, Center for Molecular Medicine (CMM), Karolinska Institute, Karolinska University Hospital, Stockholm, SwedenCentre for Rheumatology Research, Landspitali University Hospital, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, IcelandCenter for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, NorwayDivision of Medicine and Rheumatology, Helsinki University Hospital, Helsinki, Finland; University of Helsinki, Helsinki, FinlandCentre for Rheumatology Research, Landspitali University Hospital, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, IcelandDanish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark; Department of Regional Health Research, University of Southern Denmark, Odense, DenmarkDepartment of Medicine, Rheumatology Unit, Center for Molecular Medicine (CMM), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, Amsterdam, NetherlandsCopenhagen Center for Arthritis Research (COPECARE) and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkAmsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, Amsterdam, Netherlands; Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, NetherlandsCopenhagen Center for Arthritis Research (COPECARE) and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkCenter for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, NorwayUniversity of Eastern Finland, Kuopio, Finland; Hospital Nova, Wellbeing Services County of Central Finland, Jyväskylä, FinlandDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Rheumatology, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Medicine, University of California San Diego, La Jolla, CA, USADepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden; Corresponding author. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30, Gothenburg, Sweden.Objective: In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) alter their metabolism to support their activation. We aimed to analyse the full spectrum of metabolic alterations associated with RA by performing untargeted metabolomics in RA FLS vs. non-inflamed (NI) FLS. Methods: Untargeted annotated metabolomics was performed using mass spectrometry on ten primary RA and seven NI FLS culture extracts and 220 serum samples from participants with early RA from the randomised controlled NORD-STAR trial. Carnitine-related proteins were measured with Western blot. FLS bioenergetic profile was assessed with a Seahorse flux analyser. Results: Metabolomics analysis based on 138 annotated metabolites revealed a distinct metabolic fingerprint between RA and NI FLS. Of the 12 metabolites enriched in RA FLS, 11 were acylcarnitines. Pro-inflammatory stimulation of NI FLS also led to acylcarnitine accumulation. RA FLS exhibited lower levels of CD36, a fatty acid transporter, but similar levels of L-carnitine transporter, and carnitine palmitoyltransferase 1 A and 2 compared to NI FLS. Seahorse analyses showed no difference in fatty acid oxidation between RA and NI FLS; however, RA FLS displayed mitochondrial dysfunction and energetic impairment. Serum acylcarnitine content decreased after 24 weeks of treatment with methotrexate combined with abatacept or tocilizumab in patients with early RA achieving remission. Conclusion: Acylcarnitine accumulation is a characteristic of RA FLS metabolic fingerprint and could be linked to mitochondrial dysfunction. In patients with early RA, acylcarnitine content in serum decreases after successful anti-rheumatic treatment. These results indicate a dysregulation in acylcarnitine metabolism in RA at the joint level and systemically.http://www.sciencedirect.com/science/article/pii/S2589909025000450Rheumatoid arthritisFibroblast-like synoviocytesMetabolomicsAcylcarnitines |
| spellingShingle | Georgios K. Vasileiadis Yuan Zhang Marion Laudette Tahzeeb Fatima Anna-Karin Hultgård Ekwall Reshmi Sureshkumar Ronald van Vollenhoven Jon Lampa Bjorn Gudbjornsson Espen A. Haavardsholm Dan Nordström Gerdur Gröndal Kim Hørslev-Petersen Kristina Lend Merete L. Hetland Michael Nurmohamed Mikkel Østergaard Till Uhlig Tuulikki Sokka-Isler Anna Rudin Jan Borén Monica Guma Cristina Maglio Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint Journal of Translational Autoimmunity Rheumatoid arthritis Fibroblast-like synoviocytes Metabolomics Acylcarnitines |
| title | Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint |
| title_full | Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint |
| title_fullStr | Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint |
| title_full_unstemmed | Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint |
| title_short | Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint |
| title_sort | acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast like synoviocyte metabolic fingerprint |
| topic | Rheumatoid arthritis Fibroblast-like synoviocytes Metabolomics Acylcarnitines |
| url | http://www.sciencedirect.com/science/article/pii/S2589909025000450 |
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