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Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia

2021· article· en· W3201738284 on OpenAlexafffund
Vivek Verma, Gillian L. Drury, Marc Parisien, Ayşe Nur Özdağ Acarlı, Tho-Alfakar Al-Aubodah, Anastasia Nijnik, Xia Wen, Nicol Tugarinov, Maria Verner, Richie Klares, Alexander Linton, Emerson Krock, Carlos E. Morado-Urbina, Bendik S. Winsvold, Lars G. Fritsche, Egil A. Fors, Ciriaco A. Piccirillo, Arkady Khoutorsky, Camilla I. Svensson, Mary Ann Fitzcharles, Nicole F. Bernard, Franck P. Dupuy, Nurcan Üçeyler, Claudia Sommer, Irah L. King, Carolina B. Meloto, Luda Diatchenko

Bibliographic record

VenuePain · 2021
Typearticle
Languageen
FieldMedicine
TopicFibromyalgia and Chronic Fatigue Syndrome Research
Canadian institutionsMcGill University Health CentreMcGill University
FundersNational Institute of Dental and Craniofacial ResearchCanadian Institutes of Health ResearchKenneth Rainin Foundation
KeywordsImmune systemPeripheral blood mononuclear cellImmunologyFlow cytometryCD16Natural killer cellBiologyNKG2DCell biologyCytotoxic T cellIn vitroCD8CD3

Abstract

fetched live from OpenAlex

ABSTRACT: The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT. These NK cells were hyperresponsive, with increased CCL4 production and expression of CD107a when co-cultured with human leukocyte antigen null target cells. Genetic and transcriptomic pathway analyses identified significant enrichment of cell activation pathways in FMS driven by NK cells. Skin biopsies showed increased expression of NK activation ligand, unique long 16-binding protein, on subepidermal nerves of patients FMS and the presence of NK cells near peripheral nerves. Collectively, our results suggest that chronic activation and redistribution of circulating NK cells to the peripheral nerves contribute to the immunopathology associated with FMS.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.017
GPT teacher head0.282
Teacher spread0.265 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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

Citations42
Published2021
Admission routes2
Has abstractyes

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