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Record W2790038124 · doi:10.1093/jcag/gwy009.066

A66 CHARACTERIZATION OF PERIPHERAL BLOOD AND LAMINA PROPRIA LYMPHOCYTES IN CROHN’S DISEASE.

2018· article· en· W2790038124 on OpenAlexaff
Namita Power, Thurarshen Jeyalingam, Melissa Filice, Michelle I. Smith, Mark S. Silverberg, A.H. Steinhart, G C Nguyen, Petros Zezos, Kenneth Croitoru

Bibliographic record

VenueJournal of the Canadian Association of Gastroenterology · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsMount Sinai Hospital
Fundersnot available
KeywordsLamina propriaIonomycinImmunologyCD8Immune systemCrohn's diseaseIL-2 receptorFlow cytometryT cellCD3CytokineFOXP3MedicineBiologyInternal medicineStimulationPathologyDiseaseEpithelium

Abstract

fetched live from OpenAlex

Stimulation of the intestinal immune system is an important contributor to the pathogenesis of Crohn’s disease. This includes possible changes in regulatory T cells (Tregs), mucosal-associated invariant T cells (MAIT), and helper T cells (Th cells). We aimed to characterize and compare T-lymphocyte subpopulations in the peripheral blood and intestinal lamina propria (LP) of healthy individuals and those with Crohn’s disease (CD). Peripheral blood and LP biopsy specimens of the colon and ileum were collected from 33 patients with CD and 15 healthy controls (HC). Lymphocytes were isolated from the peripheral blood (PBL) and LP (LPL) and cell surface phenotype and intracellular cytokines were analyzed by flow cytometry. Specifically, we assessed markers of T cells (CD3+), Tregs (CD4+CD25+CD127-), MAIT cells (CD3+CD8+CD161high, Vα7.2+), and cells expressing α4β7 and αEβ7 integrins (Beta7+, CD103+). Cells were also stimulated with PMA and ionomycin for 4 hours at 37oC and analyzed for cell surface phenotype and intracellular cytokine expression using Ab to IFNγ, TNFα, and IL17a. When compared to HC, we found a decrease of MAIT and Tregs in the peripheral blood of CD patients (2.39% vs. 7.77%, P=0.0008; 2.8% vs. 5.9%, P<0.0001). In inflamed tissue of CD patients there was an increase in Tregs as compared to both HC and non-inflamed tissue of CD patients (3.17% vs. 1.87%, P= 0.0013; 3.17% vs. 1.86%, P=0.011). Interestingly, MAIT cell levels in LPL of HC were not significantly different from that of CD patients (3.73% vs 3.79%, P=0.6558). MAIT cells in the blood of CD patients produced more IL17a than MAIT cells from HC (5.72% vs. 2.68%, P=0.0242). Furthermore, we saw an increase in production of IL17a from α4β7 + and αEβ7 + cells in CD patients (15.3% vs. 11.83%, P=0.0401; 15.4% vs. 8.86%, P=0.0002) as well as an increase in LPL co-producing IFNγ and IL17a (5.81% vs. 3.66%, P=0.0003) and TNFα and IL17a (13.28% vs. 9.44%, P=0.0028), when compared to HC, regardless of disease activity. These data show that peripheral blood lymphocyte phenotype differs from gut LPL in HC and in CD. The increase in IFNγ-IL17a and TNFα-IL17a producing LPL suggest a disease state shift from Th1 cells to Th17 cells in CD. Taken together, these results suggest that intestinal Th17 cells can transition into Th1-like cells and pro-inflammatory stimuli may promote this conversion. It remains to be shown if therapy restores the balance of Th1 and Th17 cells. Together, these results provide insight into the immune profile of CD patients at baseline, prior to biologic treatment. AbbVie

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 score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.001

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 head0.003
GPT teacher head0.189
Teacher spread0.186 · 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

Citations0
Published2018
Admission routes1
Has abstractyes

Explore more

Same venueJournal of the Canadian Association of Gastroenterology→Same topicInflammatory Bowel Disease→French-language works237,207→