Abstract
Abstract Background Tumor necrosis factor alpha (TNF-alpha) is crucial in IBD pathogenesis: previous studies showed that its expression correlates to the degree of colonic inflammation and that its issue levels may predict response to biologic agents. This project addresses immunohistochemical (IHC) TNF-alpha expression profiles and patterns in ileal, colonic, and rectal biopsies before and after biologic therapy, matched with endoscopic and clinical severity indexes. Thus, this study aims to identiy possible histological and IHC markers predictive of drug response. Methods A cohort of ten patients with Inflammatory Bowel Disease (7 Crohn’s Disease and 3 Ulcerative Colitis) treated with biologic agents were phenotypically defined according to the Montreal classification and retrospectively characterized as responders or non- responders. These features were pioneeringly integrated with IHC quantiying TNF-alpha positivity and endoscopic severity scores (SES-CD, Mayo endoscopic subscore) aHer the collection of colonoscopy biopsy specimens. IHC TNF-alpha assessment evidenced pronounced cytoplasmic staining of inflammatory cells in the lamina propria amidst crypts and occasionally with a transmural distribution. Elevated TNF-alpha positive cells (arbitrary cut-off of ≥ 20) were chiefly observed at diagnosis or relapse in the intestinal segments affected by the disease. Results For each colonoscopy, endoscopic activity (SES-CD/Mayoendoscopic score) significantly correlated with the dichotomic number of TNF-alpha+ cells measured in the biopsies at the endoscopic (ESOD) and histologic (HSOD) site of disease (p=0,039; p=0,046). Furthermore, the number of TNF-alpha positive cells in the HSOD segment at the first check-up available during treatment was significantly associated with response to first-line biologics (p= 0,023), thus suggest whether treatment continuation was appropriate or not. Conclusion This study thoroughly examines the link between IHC investigation of TNF-alpha positivity, Montreal classification at diagnosis, and endoscopic activity indexes. TNF-alpha IHC analysis could further stratify IBD patients and increase diagnostic accuracy, securing a patent- and disease-tailored therapy and avoiding unnecessary and ineffective treatments. As an outcome, it could reduce fruitless health expenditures resulting from failed therapeutic attempts. Lastly, this evaluation could spark new possibilities for molecular biology research regarding TNF-alpha functionality on the ileocolon and further elucidate the mechanisms underlying IBD. References Villanacci V et al "Histopathology of inlammatory bowel disease- Position statement of the Pathologists of the Italian Group of the Study of the Inflammatory Bowel Disease (IG- IBD) and Italian Group of Gastrointestinal Pathologists (GIPAD-SIAPEC) " Digestive ad Liver Disease 2020 Daperno et al . "Development and validation of a new, simplified endoscopic activity score of Crohn’s Disease: the SES - CD" GIE 2002
Published Version
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