Evidence map›Paper›PMID 42735597›Full record

ArticleMultiple sclerosis and related disorders2026

Evaluation of potential serum biomarkers for individuals at risk of multiple sclerosis highlights SPP1.

Kristin Mounts, YunDuo Liu, Masashi Fujita, Juliana Oyegunle, Tradite Neziraj, Susan V Pollak, Renu Nandakumar, Nyater Ngouth, Sonya U Steele, Irene Cortese and 4 more

Abstract read
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In one paragraph

Article in Multiple sclerosis and related disorders, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Kristin MountsCenter for Translational & Computational Neuroimmunology, Division of Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
YunDuo LiuCenter for Translational & Computational Neuroimmunology, Division of Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Masashi FujitaCenter for Translational & Computational Neuroimmunology, Division of Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Juliana OyegunleCenter for Translational & Computational Neuroimmunology, Division of Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Tradite NezirajCenter for Translational & Computational Neuroimmunology, Division of Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Susan V PollakBiomarker Core Laboratory, Irving Institute for Clinical and Translational Research, Columbia University Irving Medical Center, New York, NY, United States.
Renu NandakumarBiomarker Core Laboratory, Irving Institute for Clinical and Translational Research, Columbia University Irving Medical Center, New York, NY, United States.
Nyater NgouthNeuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Sonya U SteeleNeuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Irene CorteseNeuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Charles C WhiteCenter for Translational & Computational Neuroimmunology, Division of Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Steven JacobsonNeuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Daniel S ReichNeuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Philip L De JagerCenter for Translational & Computational Neuroimmunology, Division of Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA; Multiple Sclerosis Center, Division of Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA. Electronic address: pld2115@CUIMC.columbia.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Circulating proteins have been widely investigated as potential biomarkers in multiple sclerosis (MS), yet findings across studies are often inconsistent, likely reflecting differences in disease stage, treatment exposure, and cohort composition. Studying individuals at elevated risk of MS prior to disease onset offers a unique opportunity to identify immune alterations that precede clinical disease while minimizing confounders. Here, we investigated whether alterations in six previously MS-associated biomarkers are detectable and associated with underlying genetic susceptibility in two independent sample collections consisting of persons with MS (pwMS), healthy participants, and asymptomatic first-degree relatives of pwMS from the Genes & Environment in MS (GEMS) study cohort. The panel, representing complementary axes of MS immunopathology, included granzyme A (GZMA), MER tyrosine kinase (MERTK), interleukin-2 receptor alpha (IL2RA), osteopontin (SPP1), CD30 (TNFRSF8), and chitinase-3-like protein 1 (CHI3L1). None of the proteins demonstrated associations with MS. A composite score constructed from externally derived effect estimates was associated with neither MS nor first-degree-relative status. Among asymptomatic first-degree relatives, higher genetic risk was associated with lower SPP1 levels for both the overall MS GRS and its non-MHC component, while TNFRSF8 was inversely associated with the non-MHC GRS in secondary analyses. Together, these findings suggest that several circulating proteins recently proposed as MS biomarkers are not robust tools to distinguish MS from healthy individuals. However, SPP1 levels are highlighted for further evaluation among at-risk individuals to determine whether circulating immune signatures can capture the earliest stages of MS in at-risk individuals.

Indexed as

BiomarkersFirst-degree relativesGenetic risk scoreMultiple sclerosisSerum

Identifiers

PMID42735597

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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 OpenQuestion graph.