UEG Week 2024 Oral Presentations
Notice bibliographique
Résumé
Introduction: Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic debilitating.Current clinical practice is focused on managing disease flares and complications, requiring lifelong medical treatment and/or surgery.However, a paradigm shift in IBD care is needed, moving from treatment of established disease towards creating opportunities for prevention of disease development.Such strategies recently proved successful in rheumatoid arthritis and type 1 diabetes.Before being able to achieve this, however, preclinical disease biomarkers are urgently needed.IBD is characterized by unique immunological changes early in development.Although >300 IBD-specific antibody responses have been identified 1 , systemic antibody epitope repertoires of preclinical IBD remain elusive.This study aimed to profile systemic antibody responses at unprecedented depth in individuals before and after the onset of IBD, aiming to identify preclinical disease biomarkers. Aims & Methods:This study included individuals participating in the Lifelines Cohort Study, a large prospective population-based cohort study in the Netherlands including 167,000 individuals with longitudinal follow-up.Participants without IBD at baseline were screened for any reported IBD diagnosis during follow-up (2006-2021).Individuals who reported IBD during follow-up and with available serum samples were included.Samples at baseline (pre-diagnosis) and during follow-up (post-diagnosis) were used to profile antibody repertoires against 344,000 rationally selected microbial-, food-, and immune antigens using phage-display immunoprecipitation sequencing (PhIP-Seq).Results: A total of 178 new-onset cases with IBD were identified.Median follow-up time until diagnosis was 3.9 (IQR: 3.4-4.3)years.Most individuals newly developed UC (n=123, 69.1%), followed by CD (n=44, 24.7%), and undetermined IBD (IBD-U, n=11, 6.2%).A total of 5,174 antibody responses were observed in 5-95% of participants.Fifty-nine antibodies were differentially abundant (FDR<0.05)pre-diagnosis vs. post-diagnosis, 14 of which (24%) were previously reported in established IBD 1 .Thirteen were more (22%) and 46 less (78%) frequently observed post-diagnosis.Individuals developing IBD exhibited reduced frequencies of antibody responses against EBV-associated peptides post-diagnosis, e.g.Epstein-Barr nuclear antigen-1 (EBNA-1) and capsid protein V26, and other herpesviruses including varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), and noroviruses.Conversely, significantly increased antibody responses were observed against bacterial flagellins (notably from Lachnospiraceae and pathogenic (e.g.Legionella) bacteria) in individuals developing CD, already before disease onset.Individuals developing UC showed elevated antibody responses mainly against viruses (e.g.human adenovirus C, enteroviruses B/C) and particular pathogenic bacterial species (e.g.pneumococcal histidine triad proteins) post-diagnosis compared to pre-diagnosis.Conclusion: This study represents the first comprehensive and high-resolution analysis of the exact antigenic nature of systemic antibody responses changing during the transition from preclinical to established IBD.Distinct antibody responses appear years before IBD diagnosis, indicating potential involvement in pre-clinical disease development.Furthermore, post-diagnosis, lower frequencies of antibody responses against EBV may suggest reduced immunogenicity against this virus in early disease pathogenesis.
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 | 0,005 | 0,015 |
| Méta-épidémiologie (sens strict) | 0,004 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,003 |
| Bibliométrie | 0,005 | 0,002 |
| Études des sciences et des technologies | 0,003 | 0,001 |
| Communication savante | 0,013 | 0,003 |
| Science ouverte | 0,003 | 0,003 |
| Intégrité de la recherche | 0,016 | 0,010 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,197 | 0,125 |
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 ».