A pilot study to identify blood-based markers associated with response to treatment with Vedolizumab in patients with Inflammatory Bowel Disease
Notice bibliographique
Résumé
The inflammatory bowel diseases (IBD) known as Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract believed to arise because of an imbalance between the epithelial, immune and microbial systems. It has been shown that biological differences (genetic, epigenetic, microbial, environmental, etc.) exist between patients with IBD, with multiple risk factors been associated with disease susceptibility and IBD-related phenotypes (e.g. disease location). It is also known that there is heterogeneity in terms of response to therapy in patients with IBD, including to biological therapies that target very specific biological pathways (e.g. TNF-alpha signaling, IL-23R signaling, immune cell trafficking, etc.). It is hypothesized that the better the match between the biology targeted by these advanced therapies and the predominant disease-associated pathways at play in each patient will favor a beneficial response. The aim of this pilot study was to identify potential biological differences associated with differential treatment response to the anti α4β7 integrin therapy known as Vedolizumab. Our approach was to measure a broad range of analytes in the serum of patients prior to initiation of therapy and at the first clinical assessment visit, to identify potential markers of biological differences between patients at baseline and to see which biomarkers are most affected by treatment in responders. Our focus on early clinical response was to study the most proximal effects of therapy and to minimize confounders such as loss of response that occurs further distal to treatment initiation. Specifically, we performed targeted analyses of >150 proteins and metabolites, and untargeted analyses of >1100 lipid entities, in serum samples from 92 IBD patients (42 CD, 50 UC) immediately prior to initiation of therapy with vedolizumab (baseline samples) and at their first clinical assessment (14-week samples). We found lower levels of SDF-1a, but higher levels of PDGF-ββ, lactate, lysine, phenylalanine, branched chain amino acids, alanine, short/medium chain acylcarnitines, and triglycerides containing myristic acid in baseline serum samples of responders as compared to non-responders. We also observed an increase in serum levels of CXCL9 and citrate, as well as a decrease in IL-10, between baseline and week 14 samples. In addition, we observed that a group of metabolites and protein analytes was strongly associated with both treatment response and BMI status, although BMI status was not associated with treatment response.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».