Evidence map›Paper›PMID 40918143›Full record

ArticleFrontiers in immunology2025

Discovery and early validation of serum protein signatures in untreated multiple sclerosis patients: identification of candidate biomarkers for diagnosis and stratification.

Isabel Brichette-Mieg, Ana Alonso-Torres, Pablo Aliaga-Gaspar, José-Luis Rodríguez-Bada, Virginia Reyes-Garrido, Patricia Urbaneja-Romero, Carmen Muñoz, María Díaz-Sánchez, Elisa Martín-Montañez, María-Del-Rosario Cabello-Porras and 2 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. A framework for blood biomarker discovery in MS.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
    Review
  3. Article
  4. Review
  5. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Isabel Brichette-Mieg *Neuroimmunology and Neuroinflammation Group, Biomedical Research Institute of Málaga-IBIMA Plataforma Bionand, Hospital Regional Universitario de Málaga, Málaga, Spain.
Ana Alonso-Torres *Neuroimmunology and Neuroinflammation Group, Biomedical Research Institute of Málaga-IBIMA Plataforma Bionand, Hospital Regional Universitario de Málaga, Málaga, Spain.
Pablo Aliaga-GasparNeuroimmunology and Neuroinflammation Group, Biomedical Research Institute of Málaga-IBIMA Plataforma Bionand, Hospital Regional Universitario de Málaga, Málaga, Spain.
José-Luis Rodríguez-BadaNeuroimmunology and Neuroinflammation Group, Biomedical Research Institute of Málaga-IBIMA Plataforma Bionand, Hospital Regional Universitario de Málaga, Málaga, Spain.
Virginia Reyes-GarridoNeuroimmunology and Neuroinflammation Group, Biomedical Research Institute of Málaga-IBIMA Plataforma Bionand, Hospital Regional Universitario de Málaga, Málaga, Spain.
Patricia Urbaneja-RomeroNeuroimmunology and Neuroinflammation Group, Biomedical Research Institute of Málaga-IBIMA Plataforma Bionand, Hospital Regional Universitario de Málaga, Málaga, Spain.
Carmen MuñozDepartment of Neurology, Hospital Complejo Torrecárdenas, Almería, Spain.
María Díaz-SánchezDepartment of Neurology, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Elisa Martín-MontañezDepartment of Pharmacology, Faculty of Medicine, University of Malaga, Málaga, Spain.
María-Del-Rosario Cabello-PorrasDepartment of Pharmacology, Faculty of Medicine, University of Malaga, Málaga, Spain.
Begoña Oliver-MartosNeuroimmunology and Neuroinflammation Group, Biomedical Research Institute of Málaga-IBIMA Plataforma Bionand, Hospital Regional Universitario de Málaga, Málaga, Spain.
Laura LeyvaNeuroimmunology and Neuroinflammation Group, Biomedical Research Institute of Málaga-IBIMA Plataforma Bionand, Hospital Regional Universitario de Málaga, Málaga, Spain.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Despite progress in serum biomarker research, reliable tools for early diagnosis and patient stratification in multiple sclerosis (MS) remain limited. This study uses proteomic profiling in untreated MS patients to identify early disease-associated biomarkers. Methods: We conducted an unbiased proteomic screen to capture broad serum protein expression profiles in a well-characterized discovery sample: 7 relapsing remitting MS (RRMS), 7 secondary progressive MS (SPMS), 4 with primary progressive MS (PPMS) alongside 6 healthy controls (HC). Twelve candidate biomarkers were subsequently validated by ELISA in an independent sample comprising 80 untreated MS patients (38 RRMS, 21 SPMS, 21 PPMS) and 21 age- and sex-matched HC from southern Spain. Results: In the discovery phase, 393 proteins were identified; 13 showed significant differences between MS patients and controls and 4 were dysregulated between PPMS and relapsing-onset MS (ROMS). These proteins were involved in immune responses, oxidative stress, and complement regulation. ELISA validation confirmed six differentially abundant proteins (DAPs) in MS patients compared to controls. Among these, BST1 levels were elevated in ROMS ( Conclusion: Our study identified six proteins involved in key pathological mechanisms such as inflammation, oxidative stress, immune regulation, and blood-brain barrier (BBB) integrity. Notably, the upregulation of PRDX6-linked to protein repair and neuroprotection in EAE models-may reflect a compensatory response to neuroinflammatory damage. Conversely, the downregulation of MST1, a molecule involved in immune signaling, could impair neuroprotective signaling and may drive neuroinflammation. These findings highlight PRDX6 and MST1 as particularly promising biomarkers for the diagnosis and monitoring of MS, meriting further validation in larger, longitudinal cohorts.

Indexed as

BiomarkersBlood ProteinsMultiple SclerosisMultiple Sclerosis, Chronic ProgressiveMultiple Sclerosis, Relapsing-RemittingAdultEarly DiagnosisFemaleHumansMaleMiddle AgedProteomicsBiomarkersBlood Proteinsdifferentially abundant proteinsinnate immunitymultiple sclerosisneuroinflammationoxidative stressproteomicsserum biomarkers

Identifiers

PMID40918143
PMCPMC12408279

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.