P215 Deep immune phenotyping of unconventional T cells reveals a depletion in Mucosa Associated T Cells (MAIT) in IBD patients with extraintestinal manifestations
Bibliographic record
Abstract
Abstract Background Extraintestinal manifestations (EIM) are common in IBD and they affect importantly the quality of life of patients. Although the pathogenesis of EIM is still poorly understood, an altered immune response involving T cells has been proposed. In addition, the presence of EIM during disease course will impact the therapeutic choices with new biologics. In the present work we aim to characterize T cell populations -with focus on Uncoventional T cells- in IBD patients presenting EIM using advance flow cytometry and proteomics. Methods A total of 184 individuals (106 F/78 M) and were prospectively included: 149 IBD patients (84 UC/65 CD) and 25 healthy matched controls. Biologic samples including Peripheral Blood Mononuclear Cells (PBMC) and plasma were consecutively stored and classified in an established cross sectional IBD biobank at the Norwegian University of Science and Technology. Patient characteristics including age, sex, smoking status, current medication, Montreal Classification phenotype and inflammation biomarkers (CRP) and fecal Calprotectin were recorded. PBMC were stained with antibodies and acquired using BD FACS Symphony flow cytometer using automatic compensations and Multiplex ELISA for 65 proteins was performed using Immune Monitoring 65-Plex Human ProcartaPlex™ Panel at Singapore Immunology Network (SIgN), as previously described. Statistical analysis was performed using GraphPad Prism (San Diego, CA). p≤ 0.05 was considered statistically significant. Results Of the 184 IBD patients included, the presence or not of EIM was registered in 149 (mean age 37 +/-7.2; 86 female) of which 84 had UC and 65 CD. Of them, 21 (14.1%) presented EIM at inclusion. We analyzed the differences in all subsets of unconventional T cells: gammadelta T cells (VD1, VD2, VD3), MAIT cells, innate NKT cells and CD4/CD8 positive T cells between IBD patients with or without EIM (Fig1A). MAIT cells were selectively depleted in patients with EIM (p<0.01), while there was no statistically significant change in the ratios of other T cell subpopulations. We then studied the concentrations of plasma proteins between the two groups. We found a significant increase in IL-2, GM-CSF, IL-6, Eotaxin, Leukemia Inhibitory Factor Protein (LIF), TNF-RII and Monocyte Chemoattractant Protein-1 (MCP), all p<0.05 in patients with EIM (Fig1B). In order to address the potential use of MAIT as marker of EIM we constructed a ROC curve showing an AUC 0.752 (95% CI 0.639-0.865, p= 0.0002) Fig. 1C Conclusion MAIT cell depletion associated strongly with the presence of EIM and could be used as a clinical marker for EIM in IBD. A deeper understanding of its role in the pathogenesis of EIM, as well as an external validation as a marker, deserves further investigation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".