Evidence map›Paper›PMID 38659387›Full record

ArticleBrain pathology (Zurich, Switzerland)2024

A role for vessel-associated extracellular matrix proteins in multiple sclerosis pathology.

Marco Pisa, Joseph L Watson, Jonathan I Spencer, Guy Niblett, Yasamin Mahjoub, Andrew Lockhart, Richard L Yates, Sydney A Yee, Gina Hadley, Jennifer Ruiz and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain pathology (Zurich, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.3field-weighted citation impact, top 23% of its field
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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
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

14 authors at 4 institutions in 3 countries.

Marco PisaNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.ORCID 0000-0001-9409-6864
Joseph L WatsonOxford Medical School, University of Oxford, Oxford, UK.
Jonathan I SpencerCentre for Cardiovascular Medicine and Devices, William Harvey Research Institute, Queen Mary University of London, London, UK.
Guy NiblettOxford Medical School, University of Oxford, Oxford, UK.
Yasamin MahjoubFaculty of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Andrew LockhartNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Richard L YatesNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.ORCID 0000-0002-3041-5288
Sydney A YeeNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Gina HadleyNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Jennifer RuizMandell MS Center, Trinity Health of New England, Hartford, Connecticut, USA.
Margaret M EsiriNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Benedict KesslerMass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, UK.
Roman FischerMass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, UK.
Gabriele C DeLucaNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
University of Oxford · GBQueen Mary University of London · GBTrinity Health · USUniversity of Alberta · CA

Funding

Clarendon FundMerck Serono Grant for MS InnovationNational Institute for Health Research (NIHR), Oxford Biomedical Research Centre (BRC)Oxford-Quinnipiac-Trinity Health Of New England partnership
6 · The paper itself

Abstract

Multiple sclerosis (MS) is unsurpassed for its clinical and pathological hetherogeneity, but the biological determinants of this variability are unknown. HLA-DRB1*15, the main genetic risk factor for MS, influences the severity and distribution of MS pathology. This study set out to unravel the molecular determinants of the heterogeneity of MS pathology in relation to HLA-DRB1*15 status. Shotgun proteomics from a discovery cohort of MS spinal cord samples segregated by HLA-DRB*15 status revealed overexpression of the extracellular matrix (ECM) proteins, biglycan, decorin, and prolargin in HLA-DRB*15-positive cases, adding to established literature on a role of ECM proteins in MS pathology that has heretofore lacked systematic pathological validation. These findings informed a neuropathological characterisation of these proteins in a large autopsy cohort of 41 MS cases (18 HLA-DRB1*15-positive and 23 HLA-DRB1*15-negative), and seven non-neurological controls on motor cortical, cervical and lumbar spinal cord tissue. Biglycan and decorin demonstrate a striking perivascular expression pattern in controls that is reduced in MS (-36.5%, p = 0.036 and - 24.7%, p = 0.039; respectively) in lesional and non-lesional areas. A concomitant increase in diffuse parenchymal accumulation of biglycan and decorin is seen in MS (p = 0.015 and p = 0.001, respectively), particularly in HLA-DRB1*15-positive cases (p = 0.007 and p = 0.046, respectively). Prolargin shows a faint parenchymal pattern in controls that is markedly increased in MS cases where a perivascular deposition pattern is observed (motor cortex +97.5%, p = 0.001; cervical cord +49.1%, p = 0.016). Our findings point to ECM proteins and the vascular interface playing a central role in MS pathology within and outside the plaque area. As ECM proteins are known potent pro-inflammatory molecules, their parenchymal accumulation may contribute to disease severity. This study brings to light novel factors that may contribute to the heterogeneity of the topographical variation of MS pathology.

Indexed as

BiglycanDecorinExtracellular Matrix ProteinsMultiple SclerosisSpinal CordAdultAgedCohort StudiesFemaleHLA-DRB1 ChainsHumansMaleMiddle AgedProteomicsBiglycanDecorinExtracellular Matrix ProteinsHLA-DRB1 ChainsECM proteinsHLA‐DRB1*15MSpathologytopographyvessel

Identifiers

PMID38659387
PMCPMC11483522
OpenAlexW4395455886

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.