Nardone, Olga Maria (2021) Ultra-high magnification endocytoscopy and molecular markers for defining endoscopic and histologic remission in ulcerative colitis _ An exploratory study to define deep remission. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Ultra-high magnification endocytoscopy and molecular markers for defining endoscopic and histologic remission in ulcerative colitis _ An exploratory study to define deep remission |
| Autori: | Autore Email Nardone, Olga Maria olga.nardone@libero.it |
| Data: | 14 Febbraio 2021 |
| Numero di pagine: | 97 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Medicina Clinica e Chirurgia |
| Dottorato: | Terapie avanzate biomediche e chirurgiche |
| Ciclo di dottorato: | 33 |
| Coordinatore del Corso di dottorato: | nome email Giovanni, Di Minno diminno@unina.it |
| Tutor: | nome email Castiglione, Fabiana [non definito] |
| Data: | 14 Febbraio 2021 |
| Numero di pagine: | 97 |
| Parole chiave: | ulcerative colitis; endoscopic remission; histological remission; biomarkers |
| Settori scientifico-disciplinari del MIUR: | Area 06 - Scienze mediche > MED/12 - Gastroenterologia |
| Informazioni aggiuntive: | La tesi di dottorato è stata svolta in collaborazione con l'Institute of Translational Medicine and Immunology and Immunotherapy presso l'università di Birmingham (UK) dove la sottoscritta ha praticato un periodo di 15 mesi di formazione esterna. |
| Depositato il: | 24 Feb 2021 09:47 |
| Ultima modifica: | 07 Giu 2023 10:30 |
| URI: | http://www.fedoa.unina.it/id/eprint/13949 |
Abstract
Background Endoscopic and histological remission are both important treatment goals in patients with ulcerative colitis (UC). We aimed to define cellular architecture, expression of molecular markers and their correlation with endoscopic scores assessed by ultra -high magnification endocytoscopy (ECS) and histological scores. Methods UC patients (n=29) were prospectively recruited. The correlation between ECS score (ECSS) and Mayo Endoscopic Score (MES) and with histological scores were determined. AUC were plotted to determine the best thresholds for ECSS that predicted histological remission by Robarts (RHI) and Nancy Histological Index (NHI). Soluble analytes relevant to inflammation were measured in serum and mucosal culture supernatants using Procartaplex Luminex assays and studied by Partial Least Square Discriminant Analysis and logistic model. Mucosal RNA sequencing and bioinformatics analysis were performed to define differentially expressed genes /pathways. Results ECSS correlated strongly with RHI (r= 0.89 [95% CI 0.51- 0.98] and NHI (r= 0.86 [95% CI 0.42- 0.98] but correlated poorly with MES (r= 0.28 [95% CI-0.27 – 0.70]). We identified soluble BDNF, MIP-1 α and sVCAM-1 predicted histological remission. Mucosal biopsy cultures also identified sVCAM-1 associated with healed mucosa. RNA-seq analysis identified gene expressions shared between ECSS, RHI or NHI defined healing. A number of gene expressions and pathways were identified including inflammation, metabolic and tumour suppressors that discriminated healed from non-healed mucosa . Conclusions ECS represents an interesting tool that may sit between endoscopy and histology but closer to the latter, identifies gene expression markers and pathways that are also identified by histology.
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