Mucosa associated invariant T and natural killer cells in active and budesonide treated collagenous colitis patients.

Introduction: Collagenous colitis (CC) is an inflammatory bowel disease, which usually responds to budesonide treatment. Our aim was to study the immunological background of the disease. Methods: Analyses of peripheral and mucosal MAIT (mucosa associated invariant T cells) and NK (natural killer) cells were performed with flow cytometry. Numbers of mucosal cells were calculated using immunohistochemistry. We studied the same patients with active untreated CC (au-CC) and again while in remission on budesonide treatment. Budesonide refractory patients and healthy controls were also included. The memory marker CD45R0 and activation marker CD154 and CD69 were used to further study the cells. Finally B cells, CD4+ and CD8+ T cells were also analysed. Results: The percentages of circulating CD56dimCD16+ NK cells as well as MAIT cells (CD3+TCRVa7.2+CD161+) were decreased in au-CC compared to healthy controls. This difference was not seen in the mucosa; where we instead found increased numbers of mucosal CD4+ T cells and CD8+ T cells in au-CC. Mucosal immune cell numbers were not affected by budesonide treatment. In refractory CC we found increased mucosal numbers of MAIT cells, CD4+ and CD8+ T cells compared to au-CC. Discussion: Patients with active collagenous colitis have lower percentages of circulating MAIT and NK cells. However, there was no change of these cells in the colonic mucosa. Most mucosal cell populations were increased in budesonide refractory as compared to au-CC patients, particularly the number of MAIT cells. This may indicate that T cell targeting therapy could be an alternative in budesonide refractory CC.

Prospective comparison of an adult, an intermediate pediatric and a long pediatric colonoscope in the training process of gastrointestinal fellows to achieve high-quality practice in colonoscopy.

Background: Few data are available on the influence of colonoscope type on the training process and quality of colonoscopy. We conducted this prospective observational cohort study to investigate scope suitability for starting colonoscopy training, in relation to technical competence, quality indicators, and the patient's comfort during diagnostic colonoscopy. Methods: A total of 126 consecutive patients were enrolled in the study and assigned to one of 3 groups: adult colonoscope ([AC], n=41); intermediate pediatric colonoscope ([IPC], n=43); and long pediatric colonoscope ([LPC], n=42). Primary outcomes were completeness of the examination and minutes to the cecum. Secondary outcomes included patient tolerance, position change, use of abdominal compression, loop formation, kind of loop, and overall difficulty of the procedure. Results: Cecal intubation rates were not statistically different between the groups: AC/87.8%; IPC/81.4%; and LPC/92.8%. Terminal ileal intubation rate differed significantly among the 3 groups (P=0.015) with LPC having the higher rate (66.7% vs. 60.9%/AC and 37.2%/IPC). There were significant differences in positional changes (fewer with LPC/1.36 vs. AC/2.15 and IPC/2.09, P=0.027) and midazolam administered doses (lower with LPC/0.52 vs. AC/1.07 and IPC/0.93, P=0.032). Loop formation with subsequent resolution was significantly associated with more pain for the patient with all of the 3 colonoscope types. Conclusions: The LPC performs better in trainee hands than AC and IPC in terms of reaching competency, and quality indicators show less discomfort for the patients during colonoscopic procedures (lower midazolam dose and fewer positional changes). It could be considered the most suitable scope for starting high-quality colonoscopy training.

Collagenous Colitis Mucosa Is Characterized by an Expansion of Nonsuppressive FoxP3+ T Helper Cells.

BACKGROUND AND AIM: Increased frequencies of T regulatory (Treg) cells, key players in immune regulation, have been reported in inflammatory bowel diseases, including collagenous colitis (CC). However, traditional Treg identification techniques might have misinterpreted the frequencies of Treg cells in CC. Thus, we investigated the presence of genuine Treg cells in CC. METHODS: Treg cells were analyzed in mucosal and peripheral blood samples of CC patients before and during treatment with the corticosteroid drug budesonide and in healthy controls. Samples were analyzed by flow cytometry by classifying CD3+CD4+ cells as activated FoxP3highCD45RA- Treg cells, resting FoxP3dimCD45RA+ Treg cells, and nonsuppressive FoxP3dimCD45RA- T helper cells. Traditional gating strategies that classified Treg cells as CD25highCD127low, FoxP3+CD127low, and CD4+CD25+FoxP3+ were also used to facilitate comparison with previous studies. RESULTS: Activated and resting Treg cell frequencies did not change in active CC mucosa or peripheral blood and were not affected by budesonide treatment. Instead, nonsuppressive FoxP3dimCD45RA- T helper cells were increased in active CC mucosa, and budesonide helped restore them to normal levels. In contrast, traditional Treg cell gating strategies resulted in increased Treg cell frequencies in active CC mucosa. No alterations were found in peripheral blood samples, independently of patient treatment or gating techniques. CONCLUSION: Previously reported increase of Treg cells is a result of incomplete Treg phenotyping, which included nonsuppressive FoxP3dimCD45RA- T helper cells. Because budesonide did not affect Treg percentage, its therapeutic effect in CC might involve alternative mechanisms.

Single-centre experience with anti-tumour necrosis factor treatment in budesonide-refractory microscopic colitis patients.

Background: Microscopic colitis is an inflammatory bowel disease that causes chronic, watery diarrhoea. Microscopic colitis is usually effectively treated with budesonide, but some patients are refractory. Data on alternative treatments are sparse. Aims: The purpose of this study was to retrospectively evaluate outcome of microscopic colitis patients receiving anti-tumour necrosis factor therapy at our centre. Methods: Treatment results, including side effects, for all microscopic colitis patients receiving anti-tumour necrosis factor therapy were registered at week 12 and at end of follow-up. Clinical remission was defined as a mean of <3 stools and <1 watery stools/day/week and clinical response as a 50% reduction of mean stool frequency/day/week. Induction and maintenance treatment was either adalimumab or infliximab. Results: The study cohort comprised 18 patients; mean age at diagnosis was 47 years (range 19-77). Ten and eight patients, respectively, received adalimumab and infliximab as first-line anti-tumour necrosis factor; seven patients received second-line anti-tumour necrosis factor due to non-response, loss of response or side effects. At week 12, 9/18 patients had achieved remission, 6/18 were responders and 3/18 were non-responders. Of the nine remission patients, 3/18 (16%) had long-lasting clinical remission post-induction therapy alone. Five patients (28%) (one first-line, four second-line anti-tumour necrosis factor) were in remission and one patient (6%) responded to maintenance treatment; follow-up was mean 22 (range 4-60) months. Six patients (33%) had minor, reversible side effects. Conclusions: Over half of budesonide-refractory microscopic colitis patients can achieve clinical remission or response on anti-tumour necrosis factor agents. Prospective studies are mandatory to evaluate the efficacy and safety of anti-tumour necrosis factor treatments in budesonide-refractory microscopic colitis.

How familiar are we with decision-making concerning the treatment of perforation after endoscopic mucosal resection (EMR) in the colon? A case report.

Background and study aims We describe a case of perforation after colonic endoscopic mucosal resection (EMR) that was treated conservatively. We would like to highlight the importance of decision-making mainly based on the endoscopist's point of view in combination with the surgical consultation. Although the radiological imaging is always needed, it cannot solely lead to a decision for operation. Intraperitoneal gas in computed tomography is not always associated with a hole in the endoscopic field and could be possibly explained from a "balloon" phenomenon. The amount of extraluminal air after an EMR does not correlate reciprocally with patient's pain after the procedure. Even though perforation is a radiological diagnosis and endoscopists should be aware of the common post-EMR radiological findings, the surgical examination is mandatory and should be coupled with the endoscopic opinion in order to guide appropriately the treatment in patients with acute pain.

Fecal stream diversion and mucosal cytokine levels in collagenous colitis: A case report.

In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1ß, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-γ, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.

An association study between catalase -262C>T gene polymorphism, sodium-lithium countertransport activity, insulin resistance, blood lipid parameters and their response to atorvastatin, in Greek dyslipidaemic patients and normolipidaemic controls.

This study attempted to examine the effect of a functional catalase gene polymorphism, CAT -262C>T, on sodium-lithium countertransport (Na-Li CT) activity, insulin resistance determined as the homeostasis model assessment index (HOMA-IR), blood lipid parameters (cholesterol, triglycerides, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apolipoprotein B, apolipoprotein A-I) and their response to atorvastatin, in previously characterized Greek dyslipidaemic patients and normolipidaemic controls. Putative associations were examined by running univariate analyses with a general linear model, using age, sex, smoking and hypertension as covariates. While no statistically significant associations were detected between the CAT -262C>T polymorphism and either baseline values or their modulation by atorvastatin in the patient group, HOMA-IR values were significantly (p=0.028) lower among CAT -262CC controls compared to their T allele carrier counterparts. A trend towards higher plasma triglyceride values among CAT -262CC genotypes was also detected, in both dyslipidaemic patients and normolipidaemic controls.