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Grant support

This study was funded by the "Instituto de Salud Carlos III through projects PI20/00418 (co-founded by the European Regional Development Fund/European Social Found; "A way to make future"/" Investing in your future"), and by a grant from the "Societat Catalana de Reumatologia" awarded to SR-M. VA-G was founded by an INVESTIGO contract AGAUR (Agencia de Gestion de Ayudas Universitarias y de Investigacion), within the framework of the Recovery, Transformation and Resilience Plan, financed by the European Union, Next Generation EU.

Analysis of institutional authors

Arreaza-Gil, VeronicaAuthor

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Article

A serum metabolic biomarker panel for early rheumatoid arthritis

Publicated to:Frontiers In Immunology. 14 1253913- - 2023-09-01 14(), DOI: 10.3389/fimmu.2023.1253913

Authors: Rodriguez-Muguruza, Samantha; Altuna-Coy, Antonio; Arreaza-Gil, Veronica; Mendieta-Homs, Marina; Castro-Oreiro, Sonia; Poveda-Elices, Maria Jose; del Castillo-Pinol, Nuria; Fontova-Garrofe, Ramon; Chacon, Matilde R

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Abstract

ObjectiveThere is an urgent need for novel biomarkers to improve the early diagnosis of rheumatoid arthritis (ERA). Current serum biomarkers used in the management of ERA, including rheumatoid factor and anti-cyclic citrullinated peptide (ACPA), show limited specificity and sensitivity. Here, we used metabolomics to uncover new serum biomarkers of ERA.MethodsWe applied an untargeted metabolomics approach including gas chromatography time-of-flight mass spectrometry in serum samples from an ERA cohort (n=32) and healthy controls (n=19). Metabolite set enrichment analysis was performed to explore potentially important biological pathways. Partial least squares discriminant analysis and variable importance in projection analysis were performed to construct an ERA biomarker panel.ResultsSignificant differences in the content of 11/81 serum metabolites were identified in patients with ERA. Receiver operating characteristic (ROC) analysis showed that a panel of only three metabolites (glyceric acid, lactic acid, and 3-hydroxisovaleric acid) could correctly classify 96.7% of patients with ERA, with an area under the ROC curve of 0.963 and with 94.4% specificity and 93.5% sensitivity, outperforming ACPA-based diagnosis by 2.9% and, thus, improving the preclinical detection of ERA. Aminoacyl-tRNA biosynthesis and serine, glycine, and phenylalanine metabolism were the most significant dysregulated pathways in patients with ERA.ConclusionA metabolomics serum-based biomarker panel composed of glyceric acid, lactic acid, and 3-hydroxisovaleric acid offers potential for the early clinical diagnosis of RA.

Keywords

Arthritis, rheumatoidBiomarkersBiomarkers 2DiagnosticEarly rheumatoid arthritisGlyceric acidGlyceric acidsHumansLactic acidMetabolomicsSerum

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Frontiers In Immunology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 37/181, thus managing to position itself as a Q1 (Primer Cuartil), in the category Immunology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.73, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-31, the following number of citations:

  • WoS: 3
  • Scopus: 4
  • Europe PMC: 2
  • OpenCitations: 2

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-31:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 23.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 22 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 4.3.
  • The number of mentions on the social network X (formerly Twitter): 7 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/20.500.11797/imarina9384822

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Rodriguez-Muguruza, Samantha) and Last Author (Chacon, Matilde R).

the author responsible for correspondence tasks has been Chacon, Matilde R.