scholarly journals Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kazuhiko Uchiyama ◽  
Tomohisa Takagi ◽  
Katsura Mizushima ◽  
Mariko Kajiwara-Kubota ◽  
Saori Kashiwagi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mrna Expression ◽  
Real Time Pcr ◽  
Mucosal Healing ◽  
Histological Activity ◽  
Ifn Γ ◽  
Rectal Biopsies ◽  
Relapse Group

Abstract 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-γ, 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.

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

2021 ◽  
Author(s):  
Kazuhiko Uchiyama ◽  
Tomohisa Takagi ◽  
Katsura Mizushima ◽  
Mariko Kajiwara-Kubota ◽  
Saori Kashiwagi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mrna Expression ◽  
Real Time Pcr ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Histological Activity ◽  
Rectal Biopsies ◽  
Relapse Group

Abstract 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.

scholarly journals Histological Markers of Clinical Relapse in Endoscopically Quiescent Ulcerative Colitis

2019 ◽  
Vol 26 (11) ◽  
pp. 1722-1729 ◽  
Author(s):  
David Kevans ◽  
Richard Kirsch ◽  
Callum Dargavel ◽  
Boyko Kabakchiev ◽  
Robert Riddell ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mucosal Healing ◽  
Mucosal Inflammation ◽  
Clinical Relapse ◽  
Disease Relapse ◽  
Mayo Score ◽  
Therapeutic Decisions ◽  
First Relapse ◽  
Histological Activity

Abstract Background In ulcerative colitis (UC) patients who have achieved mucosal healing, active microscopic colonic mucosal inflammation is commonly observed. We aimed to assess the association between histological activity and disease relapse in endoscopically quiescent UC. Methods Ulcerative colitis patients with endoscopically quiescent disease and ≥12 months of follow-up were included. Biopsies were reviewed for the presence of basal plasmacytosis (BPC) and active histological inflammation, defined as a Geboes score (GS) ≥3.2. Primary outcome measures were disease relapse at 18 months and time to first relapse after index colonoscopy. Results Seventy-six UC patients (51% male; mean age, 38.6 years; median follow-up [range], 75.2 [2–118] months) were included. Sixty-two percent had an endoscopic Mayo score of 0 at index colonoscopy. Basal plasmacytosis was present in 46% and active histological inflammation in 30% of subjects. Presence of BPC was associated with a significantly shorter time to disease relapse (P = 0.01). Active histological inflammation was significantly associated with clinical relapse at 18 months (P = 0.0005) and shorter time to clinical relapse (P = 0.0006). Multivariate analysis demonstrated active histological inflammation to be independently associated with clinical relapse at 18 months and time to clinical relapse. Conclusions In endoscopically quiescent UC, active histological inflammation and the presence of BPC are adjunctive histological markers associated with increased likelihood of disease relapse. Although prospective studies are required, the presence of these histological markers should be a factor considered when making therapeutic decisions in UC.

scholarly journals P125 Histological activity as a predictor of clinical outcome in ulcerative colitis: a 1-year prospective study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S200-S200
Author(s):  
B Neri ◽  
S Romeo ◽  
A Ruffa ◽  
E Calabrese ◽  
G Sena ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Prospective Study ◽  
Univariate Analysis ◽  
Predictive Marker ◽  
Clinical Indication ◽  
Clinical Activity ◽  
Clinical Relapse ◽  
Histological Activity

Abstract Background The role of histological activity in clinical management of ulcerative colitis (UC) is under investigation. Primary aim was, in a prospective study, to assess the role of histological activity as predictor of clinical relapse in a cohort of UC patients (patients) undergoing colonoscopy and followed-up for 1 year. Secondary aim was to assess the correlation between clinical, endoscopic and histological activity scores. Methods From February 2016 to February 2017 consecutive UC patients with clinical indication for colonoscopy were enrolled and clinically followed-up for 1 year. Inclusion criteria: (1) UC diagnosis; (2) Age > 18, ≤ 80 years; (3) regular follow-up; (4) indication for colonoscopy. During colonoscopy ≥2 biopsies was taken from ≥1 macroscopically involved and, possibly, from ≥1 uninvolved area. The day of colonoscopy clinical activity was assessed by the Mayo partial score, endoscopic activity by the Mayo endoscopic score, histological activity by the Geboes Simplified Score (GSS). Scores blindly assessed by three investigators. Statistical analysis: data expressed as mean [range], Spearman’s correlation coefficients, Cox hazards regression model used for univariate and multivariate analyses to identify predictors of clinical relapse at 1 year (HR[95% CI]). Results UC cohort included 77 UC patients. Characteristics of these 77 UC patients: 43 (55.8%) males, age 51 [24–80]; UC duration 14.7 [1–48] years. UC extent included n (%): 33 (42.8%) pancolitis, 24 (31.2%) left-sided, 20 (26%) proctitis. The day of colonoscopy, UC was clinically active in 15 (19.4%), inactive in 62 (80.6%) patients. Endoscopic activity was observed in 39 (50.6%) patients, histological activity (GSS≥ 3.1) in 37(48%) patients. Moderate correlations were observed between clinical and endoscopic scores (r = 0.439;p < 0.0001) clinical and histological scores (r = 0.32;p = 0.0045), endoscopic and histological scores (r = 0.653;p < 0.0001). During the clinical follow-up at 1 year, UC clinical relapse occurred in 24 (31%) patients, while 53 (69%) patients maintained clinical remission. At baseline colonoscopy, 11/24 (46%) UC patients were clinically active, 15/24 (63%) showed endoscopic activity and 16/24 (67%) patients histological activity. Univariate analysis identified clinical activity (HR 4.82 [2.15–10.82]; p < 0.001) and histological activity (HR 2.599 [1.11–6.08]; p < 0.027) as significant predictive factors for clinical relapse at 1 year. Multivariate model confirmed histological activity as predictive marker of clinical relapse (HR 2.44 [1.04–5.75]; p < 0.041). Conclusion Histological activity provided independent information for clinical relapse in a cohort of UC patients prospectively followed up for 1 year. Histological activity had a significant correlation with the endoscopic and clinical activity scores.

scholarly journals Narrow band imaging efficiency in evaluation of mucosal healing/relapse of ulcerative colitis

2018 ◽  
Vol 06 (05) ◽  
pp. E518-E523 ◽  
Author(s):  
Seiko Sasanuma ◽  
Kazuo Ohtsuka ◽  
Shin-ei Kudo ◽  
Noriyuki Ogata ◽  
Yasuharu Maeda ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Blood Vessels ◽  
Narrow Band ◽  
Narrow Band Imaging ◽  
Mucosal Healing ◽  
Current Treatment ◽  
Mayo Score ◽  
Histological Activity ◽  
Histological Remission

Abstract Background and study aims Mucosal healing is a current treatment target in ulcerative colitis (UC), while histological remission is another target. The aim of this study was to evaluate the efficiency of magnified narrow band imaging (NBI) findings of mucosal healing and their relationship with histological activity and prognosis. Patients and methods Patients with UC who underwent total colonoscopy between January 2010 and December 2012 with left-sided or total-colitis type UC and achieved clinical remission with an endoscopic Mayo score of 0 or 1 were included. Each colon section was observed with white light and magnified NBI, with the colonoscopy being repeated at 1-year follow-up. We assessed the relationships of magnified NBI with histological disease activity and prognosis. Magnified NBI findings were divided into three categories; honeycomb-like blood vessels (BV-H), blood vessels shaped like bare branches (BV-BB), and blood vessels shaped like vines (BV-V). Results Fifty-two patients were included. The percentage of remitted mucosa with BV-BB was 37 %, while that of mucosa with scars with BV-H was 35 %. BV-H and BV-BB did not show pathological activity (12/292 and 8/299, respectively), while BV-V showed high pathological activity (27/33, 81 %). There was a correlation between magnified NBI findings and pathological findings (P < 0.01). The odds ratio for inflammation activity at 1-year follow-up was 14.2 for BV-BB (95 % CI, 3.3 – 60.9) Conclusion Magnified NBI findings showed a good relationship with histological activity. This suggests that we could estimate histological activity without biopsy, and also the possibility of predicting relapse over the following year.

Overview of Biological Therapy in Ulcerative Colitis: Current and Future Directions

2015 ◽  
Vol 24 (2) ◽  
pp. 203-213 ◽  
Author(s):  
Federica Furfaro ◽  
Cristina Bezzio ◽  
Sandro Ardizzone ◽  
Alessandro Massari ◽  
Roberto De Franchis ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Immunosuppressive Agents ◽  
Mucosal Healing ◽  
Aminosalicylic Acid ◽  
Proinflammatory Mediators ◽  
Experimental Drugs ◽  
New Treatments ◽  
Aggressive Clinical Course ◽  
Near Future

The treatment of ulcerative colitis (UC) has changed over the last decade. It is extremely important to optimize the therapies which are available nowadays and commonly used in daily clinical practice, as well as to stimulate the search for more powerful drugs for the induction and maintenance of sustained and durable remission, thus preventing further complications. Therefore, it is mandatory to identify the patients' prognostic variables associated with an aggressive clinical course and to test the most potent therapies accordingly.To date, the conventional therapeutic approach based on corticosteroids, salicylates (sulfasalazine, 5-aminosalicylic acid) or immunosuppressive agents is commonly used as a first step to induce and to maintain remission. However, in recent years, knowledge of new pathogenetic mechanisms of ulcerative colitis have allowed us to find new therapeutic targets leading to the development of new treatments that directly target proinflammatory mediators, such as TNF-alpha, cytokines, membrane migration agents, cellular therapies.The aim of this review is to provide the most significant data regarding the therapeutic role of drugs in UC and to give an overview of biological and experimental drugs that will become available in the near future. In particular, we will analyse the role of these drugs in the treatment of acute flare and maintenance of UC, as well as its importance in mucosal healing and in treating patients at a high risk of relapse.

Serpin B1 protects colonic epithelial cell via blockage of neutrophil elastase activity and its expression is enhanced in patients with ulcerative colitis

2012 ◽  
Vol 302 (10) ◽  
pp. G1163-G1170 ◽  
Author(s):  
Kazuhiko Uchiyama ◽  
Yuji Naito ◽  
Tomohisa Takagi ◽  
Katsura Mizushima ◽  
Yasuko Hirai ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mrna Expression ◽  
Real Time ◽  
Neutrophil Elastase ◽  
Colonic Mucosa ◽  
Clinical Samples ◽  
Active Ulcerative Colitis ◽  
Inflammatory Infiltration ◽  
Serpin B1

Serpin B1 is a monocyte neutrophil elastase (NE) inhibitor and is one of the most efficient inhibitors of NE. In the present study, we investigated the role of serpin B1 in the pathogenesis of ulcerative colitis by using clinical samples and an experimental model. The colonic expression of serpin B1 was determined by real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistological studies in both normal and inflamed mucosa from patients with ulcerative colitis. Serpin B1 mRNA expression was determined by real-time PCR in the mouse dextran sodium sulfate (DSS)-induced colitis model. Young adult mouse colonic epithelial (YAMC) cells were used to determine the role of serpin B1. Serpin B1 gene transfected YAMC cells were treated with H2O2 to measure cell viability. The expression of NE was determined in YAMC cells treated with H2O2. NE-silenced YAMC cells were also treated with H2O2 and then measured for viability. Upregulated expression of serpin B1 in colonic mucosa was confirmed from patients with active ulcerative colitis. Immunohistochemical studies showed that serpin B1 expression was localized not only in inflammatory infiltration cells but also in epithelial cells. Serpin B1 mRNA expression was also increased in colonic mucosa of mouse DSS-induced colitis. Serpin B1-transfected YAMC cells were resistant against the treatment of H2O2. H2O2 treatment significantly induced NE in YAMC cells, and NE-silenced YAMC cells were also resistant against the treatment of H2O2. These results suggest that serpin B1 may be a novel marker of active ulcerative colitis and may play an important role in the pathogenesis of inflammatory bowel disease.

scholarly journals OP26 The first real-life multicentre prospective validation study of the electronic chromoendoscopy score (Paddington International Virtual ChromoendoScopy ScOre) and its outcome in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S023-S024 ◽  
Author(s):  
M Iacucci ◽  
S C Smith ◽  
A Bazarova ◽  
U N Shivaji ◽  
P Bhandari ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Validation Study ◽  
Real Life ◽  
Mucosal Healing ◽  
Vascular Changes ◽  
Important Goal ◽  
Kaplan Meier ◽  
Virtual Chromoendoscopy

Abstract Background Mucosal healing is an important goal in the treatment of ulcerative colitis (UC). The newly published PICaSSO score characterises subtle mucosal and vascular changes and defines mucosal healing. We aimed to validate in real-life the PICaSSO score and assess its ability to predict relapse. Methods Patients with UC were prospectively recruited from 11 international centres. Participating endoscopists experienced in IBD received training on PICaSSO before starting the study. The rectum and sigmoid were examined using iScan 1,2 and 3 (Pentax, Japan) and inflammatory activity was assessed using UCEIS and PICaSSO. Biopsies were taken for the histological assessment using Robarts Histological Index (RHI) and Nancy. Follow-up was obtained at 12 months. Results A total of 278 patients were recruited (Table 1). The diagnostic performance in predicting histologic healing is shown in Table 2. When using PICaSSO score of ≤3 for mucosal and vascular architecture the AUROC to predict healing by RHI is 0.79 (95% CI 0.74–0.85) and 0.73 (95% CI 0.68–0.80) respectively and when using the Nancy score the AUROC is 0.78 (95% CI 0.72–0.84) and 0.77 (0.71–0.84). A total PICaSSO score of ≤8 and UCEIS score of ≤1 predicts remission at 12 months with an AUROC of 0.73 (0.65–0.80) and 0.71 (0.64–0.79). A Kaplan–Meier curve shows a favourable survival probability without relapse with a PICASSO score of ≤8 (Figure 1). Conclusion This real-life validation study shows the PICaSSO score can predict accurately histological healing and long-term remission and can be a useful tool in the management of UC.

scholarly journals MODERATE TO SEVERE ENDOSCOPIC INFLAMMATION IS FREQUENT AFTER ACHIEVING CLINICAL REMISSION IN PEDIATRIC ULCERATIVE COLITIS

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S13-S13
Author(s):  
Chen Sarbagili-Shabat ◽  
Dror Weiner ◽  
Joram Wardi ◽  
Lee Abramas ◽  
Michal Yaakov ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Residual Disease ◽  
Activity Index ◽  
Final Analysis ◽  
Mucosal Healing ◽  
Sustained Remission ◽  
High Relapse Rate ◽  
Mayo Score

Abstract Background Pediatric ulcerative colitis (UC) is characterized by low sustained remission rates and frequent extension of disease even if clinical remission is obtained with therapy. Moderate to severe endoscopic activity is a risk factor for relapse while evidence regarding early mucosal healing or persistence of inflammation after remission in children is not available. Our aim was to evaluate if persistence of significant inflammation is common and could explain the high relapse rate in pediatric UC. Methods Pediatric UC patients with clinical remission, defined as pediatric UC activity index (PUCAI) scores &lt; 10, were prospectively assessed for mucosal healing by endoscopy 3–5 months after remission was documented. Mayo score was assessed for each segment by a blinded adult gastroenterologist using central reading. Symptomatic patients prior to sigmoidoscopy were excluded Sustained remission was assessed retrospectively at 18 months follow-up. Results Forty-six children were enrolled, 28 children in continuous clinical remission at time of sigmoidoscopy were included in the final analysis. Mayo 0 was present in 12/28 (42.86%), Mayo 1 in 2/28 (7.1%) and Mayo 2–3 in 14/28 (50.0%) endoscopies. Among 23/28 patients with follow-up through 18 months, remission was sustained in 2/11 (18.18%) of patients with Mayo 2 and 3 versus 6/12 (50.0%) with Mayo score 0–1. Conclusion Over 50% of children assessed for mucosal healing 3–5 months after clinical remission is obtained have residual disease activity, primarily moderate to severe inflammation which was associated with lower sustained remission. Early sigmoidoscopy after clinical remission for assessment of mucosal disease should be considered in pediatric UC.

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