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
Patients with UC (n = 29) were prospectively recruited. The correlation among ECS score (ECSS), Mayo endoscopic score (MES), and histological scores were determined. Area under curve 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
Endocytoscope scoring system 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 brain-derived neurotrophic factors (BDNF), macrophage inflammatory proteins (MIP-1 α) and soluble vascular cell adhesion molecule 1 (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 and metabolic and tumor suppressors that discriminated healed from nonhealed mucosa.
Conclusions
Endocytoscopy represents an interesting tool that may sit between endoscopy and histology—but closer to the latter—identifying gene expression markers and pathways that are also identified by histology.
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1 Institute of Immunology & Immunotherapy University of Birmingham, Birmingham, UK; NIHR Wellcome Trust Clinical Research Facilities University Hospitals Birmingham NHS Trust, University of Birmingham, Birmingham, UK; NIHR Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
2 Institute of Immunology & Immunotherapy University of Birmingham, Birmingham, UK
3 Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham, Birmingham, UK; Institute of Translational Medicine, University of Birmingham, Birmingham, UK; NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospital Birmingham, Birmingham
4 University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
5 Institute for Biological Physics, University of Cologne, Cologne, Germany
6 Institute of Immunology & Immunotherapy University of Birmingham, Birmingham, UK; NIHR Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
7 Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham, Birmingham, UK; Institute of Translational Medicine, University of Birmingham, Birmingham, UK
8 Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham, Birmingham, UK; Institute of Translational Medicine, University of Birmingham, Birmingham, UK; NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospital Birmingham, Birmingham; MRC Health Data Research UK (HDR), Birmingham, UK
9 Institute of Immunology & Immunotherapy University of Birmingham, Birmingham, UK; NIHR Wellcome Trust Clinical Research Facilities University Hospitals Birmingham NHS Trust, University of Birmingham, Birmingham, UK; NIHR Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland