Mucosal gene transcription of ulcerative colitis in endoscopic remission

Arkteg, Christian Børde; Goll, Rasmus; Gundersen, Mona D.; Anderssen, Endre; Fenton, Christopher Graham; Florholmen, Jon

doi:10.1080/00365521.2019.1710245

Cited by 10 publications

(10 citation statements)

References 44 publications

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“…Several reports concerning the molecular background of endoscopic evaluation and clinical outcomes have been published. It has been reported that mRNA expression of mucosal cytokines, such as IL-33, IL-6, and IL-10, was upregulated in patients with an MES of 1 compared to those with an MES of 0 [23]. Although this study did not investigate the relationship between clinical outcome and mucosal cytokine expression, it has been revealed that colonic mucosa diagnosed as MES 1 had a different cytokine pro le than those diagnosed as MES 0.…”

Section: Discussionmentioning

confidence: 67%

Increased Mucosal IL-12 Expression is Associated with Relapse of Ulcerative Colitis

Uchiyama

Takagi

Mizushima

et al. 2021

Preprint

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Background: The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse.Methods: Rectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-g, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively. Results: The longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the “relapse” group, while those from patients that did not relapse formed the “remission” group. IL-12 (P=0.0003) and IL-23 (P=0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P=0.015) but not IL-12 (P=0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P=0.0015, P=0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12: P=0.0002, IL-23: P=0.046).Conclusions: Rectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse.

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Section: Discussionmentioning

confidence: 67%

Increased Mucosal IL-12 Expression is Associated with Relapse of Ulcerative Colitis

Uchiyama

Takagi

Mizushima

et al. 2021

Preprint

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“…Of note, STAT3 is a recognized proinflammatory transcripts. 34 It is known that the differentiation of Th17 cells typically requires the cytokines signaling via the STAT3 transcription activator. 35 STAT3 was upregulated in CD4þ naive T cell of UC and SC, which was also consistent with the change of Th17 cell and IL-17 signal in systemic inflammation.…”

Section: The Th17 Cell Was the Major Immune Characteristic Of Uc But Immunoglobulin A Was The Key Local Immune Component Of Inflamed Tissmentioning

confidence: 99%

Identification of Novel Population-Specific Cell Subsets in Chinese Ulcerative Colitis Patients Using Single-Cell RNA Sequencing

Zhang

Hao

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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Background & Aims Genome-wide association studies (GWAS) and transcriptome analyses have been performed to better understand the pathogenesis of ulcerative colitis (UC). However, current studies mainly focus on European ancestry, highlighting a great need to identify the key genes, pathways and cell types in colonic mucosal cells of adult UC patients from other ancestries. Here we aimed to identify key genes and cell types in colonic mucosal of UC. Methods We performed Single-cell RNA sequencing (scRNA-seq) analysis of 12 colon biopsies of UC patients and healthy controls from Chinese Han ancestry. Results Two novel plasma subsets were identified. Five epithelial/stromal and three immune cell subsets show significant difference in abundance between inflamed and non-inflamed samples. In general, UC risk genes show consistent expression alteration in both Immune cells of inflamed and non-inflamed tissues. As one of the exceptions, IgA defection, marking the signal of immune dysfunction, is specific to the inflamed area. Moreover, Th17 derived activation was observed in both epithelial cell lineage and immune cell lineage of UC patients as compared to controls , suggesting a systemic change of immune activities driven by Th17. The UC risk genes show enrichment in progenitors, glial cells and immune cells, and drug-target genes are differentially expressed in antigen presenting cells. Conclusions Our work identifies novel population-specific plasma cell molecular signatures of UC. The transcriptional signature of UC is shared in immune cells from both inflamed and non-inflamed tissues, whereas the transcriptional response to disease is a local effect only in inflamed epithelial/stromal cells.

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“…In the present study, we measured the expression of the genes SMAD7, TNF, TLR2, TNFRSF1B, TBX21, DEFA5, IL11, TREM1, and OSM (previously studied as related to the anti-TNF response or IBD in adults) [25,[27][28][29][30][31] in the whole blood of children with IBD before and after 2 weeks of anti-TNF treatment. The aim was to evaluate whether these genes could be very early pharmacogenomics biomarkers of response to anti-TNF agents in pIBD.…”

Section: Introductionmentioning

confidence: 99%

Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

Salvador-Martín

Raposo-Gutiérrez

Navas-López

et al. 2020

IJMS

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Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.

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Mucosal gene transcription of ulcerative colitis in endoscopic remission

Cited by 10 publications

References 44 publications

Increased Mucosal IL-12 Expression is Associated with Relapse of Ulcerative Colitis

Increased Mucosal IL-12 Expression is Associated with Relapse of Ulcerative Colitis

Identification of Novel Population-Specific Cell Subsets in Chinese Ulcerative Colitis Patients Using Single-Cell RNA Sequencing

Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

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