Dataset Information

Myeloid cell influx into the colonic epithelium is associated with disease severity and non-response to anti-Tumor Necrosis Factor Therapy in patients with Ulcerative Colitis.

ABSTRACT: Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon with sharply rising global prevalence. Dysfunctional epithelial compartment (EC) dynamics are implicated in UC pathogenesis although EC-specific studies are sparse. Applying orthogonal high-dimensional EC profiling to a Primary Cohort (PC; n=222), we detail major epithelial and immune cell perturbations in active UC. Prominently, reduced frequencies of mature BEST4⁺OTOP2⁺ absorptive and BEST2⁺WFDC2⁺ secretory epithelial enterocytes were associated with the replacement of homeostatic, resident TRDC⁺KLRD1⁺HOPX⁺ γδ⁺ T cells with RORA⁺CCL20⁺S100A4⁺ T_H17 cells and the influx of inflammatory myeloid cells. The EC transcriptome (exemplified by S100A8, HIF1A, TREM1, CXCR1) correlated with clinical, endoscopic, and histological severity of UC in an independent validation cohort (n=649). Furthermore, therapeutic relevance of the observed cellular and transcriptomic changes was investigated in 3 additional published UC cohorts (n=23, 48 and 204 respectively) to reveal that non-response to anti-Tumor Necrosis Factor (anti-TNF) therapy was associated with EC related myeloid cell perturbations. Altogether, these data provide high resolution mapping of the EC to facilitate therapeutic decision-making and personalization of therapy in patients with UC.

SUBMITTER: Jha D

PROVIDER: S-EPMC10274630 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Myeloid cell influx into the colonic epithelium is associated with disease severity and non-response to anti-Tumor Necrosis Factor Therapy in patients with Ulcerative Colitis.

Jha Divya D Al-Taie Zainab Z Krek Azra A Eshghi Shadi Toghi ST Fantou Aurelie A Laurent Thomas T Tankelevich Michael M Cao Xuan X Meringer Hadar H Livanos Alexandra E AE Tokuyama Minami M Cossarini Francesca F Bourreille Arnaud A Josien Regis R Hou Ruixue R Canales-Herrerias Pablo P Ungaro Ryan C RC Kayal Maia M Marion James J Polydorides Alexandros D AD Ko Huaibin M HM D'souza Darwin D Merand Raphael R Kim-Schulze Seunghee S Hackney Jason A JA Nguyen Allen A McBride Jacqueline M JM Yuan Guo-Cheng GC Colombel Jean Frederic JF Martin Jerome C JC Argmann Carmen C Suárez-Fariñas Mayte M Petralia Francesca F Mehandru Saurabh S

bioRxiv : the preprint server for biology 20230605

Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon with sharply rising global prevalence. Dysfunctional epithelial compartment (EC) dynamics are implicated in UC pathogenesis although EC-specific studies are sparse. Applying orthogonal high-dimensional EC profiling to a Primary Cohort (PC; n=222), we detail major epithelial and immune cell perturbations in active UC. Prominently, reduced frequencies of mature BEST4+OTOP2+ absorp ...[more]

PMID: 37333091

Similar Datasets

Project description:BackgroundVariability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC).ObjectiveTo evaluate variation in the overall endoscopic assessment of severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated.DesignA two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0-11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC. In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors. In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0-100 visual analogue scale. κ Statistics tested inter- and intraobserver variability for each descriptor. A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors.ResultsThere was 76% agreement for 'severe', but 27% agreement for 'normal' appearances between phase I investigators and the central reader. In phase 2, weighted κ values ranged from 0.34 to 0.65 and 0.30 to 0.45 within and between observers for the 10 descriptors. The final model incorporated vascular pattern, (normal/patchy/complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR(2), Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity).ConclusionThe Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC. Validity and responsiveness need further testing before it can be applied as an outcome measure in clinical trials or clinical practice.

Dataset Information

Myeloid cell influx into the colonic epithelium is associated with disease severity and non-response to anti-Tumor Necrosis Factor Therapy in patients with Ulcerative Colitis.

Publications

Myeloid cell influx into the colonic epithelium is associated with disease severity and non-response to anti-Tumor Necrosis Factor Therapy in patients with Ulcerative Colitis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets