Evidence map›Paper›PMID 42647758›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2026

Distinct Multiomic Signatures of Environmental Exposure Drive Immune Dysregulation and Disease Activity in Early Multiple Sclerosis.

Simon Falk, Andreas Schulte-Mecklenbeck, Patrick Ostkamp, Timo Wirth, Tilman Schneider-Hohendorf, Marie Deffner, Julia Krämer, Catharina Korsukewitz, Luisa Klotz, Catharina C Gross and 2 more

Abstract read
In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 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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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Simon FalkDepartment of Neurology, University of Muenster, Germany; and.ORCID 0009-0008-7942-5461
Andreas Schulte-MecklenbeckDepartment of Neurology, University of Muenster, Germany; and.ORCID 0000-0003-3855-4706
Patrick OstkampDepartment of Neurology, University of Muenster, Germany; and.ORCID 0000-0002-2634-4173
Timo WirthDepartment of Neurology, University of Muenster, Germany; and.
Tilman Schneider-HohendorfDepartment of Neurology, University of Muenster, Germany; and.ORCID 0000-0002-3717-5176
Marie DeffnerDepartment of Neurology, University of Muenster, Germany; and.ORCID 0009-0001-8809-1191
Julia KrämerDepartment of Neurology, University of Muenster, Germany; and.ORCID 0000-0003-2219-5593
Catharina KorsukewitzDepartment of Neurology, University of Muenster, Germany; and.
Luisa KlotzDepartment of Neurology, University of Muenster, Germany; and.ORCID 0000-0001-5439-9633
Catharina C GrossDepartment of Neurology, University of Muenster, Germany; and.ORCID 0000-0002-4872-9189
Heinz WiendlDepartment of Neurology and Neurophysiology, Medical Center, University of Freiburg, Germany.ORCID 0000-0003-4310-3432
Nicholas SchwabDepartment of Neurology, University of Muenster, Germany; and.ORCID 0000-0001-5494-9885

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesEnvironmental factors are pivotal in determining multiple sclerosis (MS) susceptibility, yet their specific influence on the immune system at the time of diagnosis remains incompletely understood. The aim of this study was to map the systemic effects of modifiable risk factors, specifically smoking, body mass index (BMI), serum vitamin D, UV exposure, and latent viral immunity, on immune function in patients with treatment-naive MS.

methodsA multiomics analysis was performed on a monocentric cohort of 96 treatment-naive patients. The study used a combination of bulk transcriptomics across 6 immune cell lineages, serum proteomics, cell-cell communication modeling, and high-dimensional flow cytometry to identify unique immunologic patterns linking environmental exposures to disease pathology.

resultsSmoking was found to induce an upregulation of the tissue-homing receptor GPR15 across lineages, particularly in NK cells, which correlated with higher disability levels. Smoking also amplified a proinflammatory milieu (increased CXCL17 and LAMP3). Higher potential UV exposure seemed to counteract these effects by lowering IFI30 and LYZ expression; notably, elevated IFI30 correlated with the presence of gadolinium-enhancing lesions. Regarding metabolic factors, high BMI exerted a linear effect on monocyte metabolism, driving cholesterol biosynthesis (MVD and SQLE) and increasing proinflammatory markers (FABP4 and LEP) associated with blood-brain barrier compromise. DISCUSSION: These findings elucidate the molecular mechanisms by which modifiable risk factors contribute to MS pathology. The data imply distinct clinical approaches for risk management: while smoking cessation must likely be absolute to reverse pathogenic trafficking signals (such as GPR15 upregulation), the linear effect of BMI suggests that incremental weight loss confers proportional immunologic benefits. These insights strongly support the integration of lifestyle interventions as a core component of early MS management.

Indexed as

Environmental ExposureMultiple SclerosisSmokingAdultBody Mass IndexCohort StudiesFemaleHumansMaleMiddle AgedMultiomicsVitamin DVitamin D

Identifiers

PMID42647758
PMCPMC13520201

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