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Record W3128676251 · doi:10.1177/1352458521989090

Pro-inflammatory adiponectin in pediatric-onset multiple sclerosis

2021· article· en· W3128676251 on OpenAlexafffund
Giulia Fadda, Luke M. Healy, Ina Mexhitaj, Laurence Poliquin‐Lasnier, Heather Hanwell, Alexander Saveriano, Ayal Rozenberg, Rui Li, Craig S. Moore, Chahrazed Belabani, Trina Johnson, Julia O’Mahony, Douglas L. Arnold, E. Ann Yeh, Ruth Ann Marrie, Shannon E. Dunn, Brenda Banwell, Amit Bar‐Or

Bibliographic record

VenueMultiple Sclerosis Journal · 2021
Typearticle
Languageen
FieldMedicine
TopicAdipokines, Inflammation, and Metabolic Diseases
Canadian institutionsUniversity of ManitobaMemorial University of NewfoundlandMontreal Neurological Institute and HospitalSickKids FoundationUniversity of TorontoMcGill UniversityHospital for Sick ChildrenInstitute of Infection and Immunity
FundersNational Institutes of HealthImmune Tolerance NetworkCanadian Institutes of Health ResearchMultiple Sclerosis Scientific Research FoundationMultiple Sclerosis Society of CanadaAmerican Academy of NeurologyUniversity of PennsylvaniaNational Multiple Sclerosis Society
KeywordsAdipokineMultiple sclerosisMedicineMicrogliaAdiponectinCD14ImmunologyImmune systemInflammationMyeloidInternal medicineEndocrinologyLeptin

Abstract

fetched live from OpenAlex

Background: Being obese is associated with both increased risk of developing multiple sclerosis (MS) and greater MS disease activity. Objectives: The objective of this study is to investigate levels and potential pathophysiologic contribution of serum adipose-hormones (adipokines) in pediatric-onset MS. Methods: Following a Luminex adipokine screen, adiponectin (APN) and its isoforms were quantified by enzyme-linked immunosorbent assay (ELISA) in 169 children with incident acquired demyelinating syndromes (ADS), prospectively ascertained as having either MS or other forms of inflammatory central nervous system (CNS) demyelination. The effect of recombinant APN and APN-containing sera was assessed on functional responses of normal human peripheral blood myeloid and T cells and on human CNS-derived microglia. Results: Compared to other cohorts, children with MS harbored higher serum APN levels, principally driven by higher levels of the low-molecular-weight isoform. Recombinant APN and pediatric MS serum-induced APN-dependent pro-inflammatory activation of CD14 + monocytes and of activated CD4 + and CD8 + T cells (both directly and indirectly through myeloid cells). APN induced human microglia activation while inhibiting their expression of molecules associated with quiescence. Conclusions: Elevated APN levels in children with MS may contribute to enhanced pro-inflammatory states of innate and adaptive peripheral immune responses and breach CNS-resident microglia quiescence, providing a plausible and potentially targetable mechanism by which APN contributes to MS disease activity.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.016
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.058
GPT teacher head0.258
Teacher spread0.200 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations12
Published2021
Admission routes2
Has abstractyes

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Same venueMultiple Sclerosis JournalSame topicAdipokines, Inflammation, and Metabolic DiseasesFrench-language works237,207