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Record W2990370852 · doi:10.1016/j.jcmgh.2019.11.012

Analysis of Flagellin-Specific Adaptive Immunity Reveals Links to Dysbiosis in Patients With Inflammatory Bowel Disease

2019· article· en· W2990370852 on OpenAlexafffund
Laura Cook, Daniel J. Lisko, May Q. Wong, Rosa V. Garcia, Megan E. Himmel, Ernest G. Seidman, Brian Bressler, Megan K. Levings, Theodore S. Steiner

Bibliographic record

VenueCellular and Molecular Gastroenterology and Hepatology · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGut microbiota and health
Canadian institutionsCanadian Society of Intestinal ResearchBC Children's HospitalMcGill UniversityUniversity of British Columbia
FundersCanadian Institutes of Health ResearchTakeda Pharmaceutical CompanyCrohn's and Colitis FoundationPfizer CanadaMerckBristol-Myers Squibb CanadaGilead SciencesCanada Research ChairsCrohn's and Colitis Foundation of America
KeywordsFlagellinDysbiosisInflammatory bowel diseaseAcquired immune systemImmunityImmunologyDiseaseMedicineImmune systemGut floraInternal medicine

Abstract

fetched live from OpenAlex

Background & Aims Bacterial flagellin is an important antigen in inflammatory bowel disease, but the role of flagellin-specific CD4 + T cells in disease pathogenesis remains unclear. Also unknown is how changes in intestinal microbiome intersect with those in microbiota-specific CD4 + T cells. We aimed to quantify and characterize flagellin-specific CD4 + T cells in Crohn's disease (CD) and ulcerative colitis (UC) patients and study their relationship with intestinal microbiome diversity. Methods Blood was collected from 3 cohorts that included CD patients, UC patients, and healthy controls. Flow cytometry analyzed CD4 + T cells specific for Lachnospiraceae -derived A4-Fla2 and Escherichia coli H18 FliC flagellins, or control vaccine antigens. Serum antiflagellin IgG and IgA antibodies were detected by enzyme-linked immunosorbent assay and stool samples were collected and subjected to 16S ribosomal DNA sequencing. Results Compared with healthy controls, CD and UC patients had lower frequencies of vaccine-antigen–specific CD4 + T cells and, as a proportion of vaccine-specific cells, higher frequencies of flagellin-specific CD4 + T cells. The proportion of flagellin-specific CD4 + T cells that were CXCR3 neg CCR4 + CCR6 + Th17 cells was reduced in CD and UC patients, with increased proportions of CD39 + , PD-1 + , and integrin β7 + cells. Microbiome analysis showed differentially abundant bacterial species in patient groups that correlated with immune responses to flagellin. Conclusions Both CD and UC patients have relative increases in the proportion of circulating Fla2-specific CD4 + T cells, which may be associated with changes in the intestinal microbiome. Evidence that the phenotype of these cells strongly correlate with disease severity provides insight into the potential roles of flagellin-specific CD4 + T cells in inflammatory bowel disease.

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)0.001
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.004
GPT teacher head0.193
Teacher spread0.189 · 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

Citations40
Published2019
Admission routes2
Has abstractyes

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