炎症性肠病内镜活检标本的诊断及鉴别诊断

目的探讨炎症性肠病(inflammatory bowel disease,IBD)内镜活检标本的病理诊断及鉴别诊断。方法对209例内镜下活检诊断为IBD的HE切片重新阅片,按照系统性诊断步骤,即组织结构、上皮及固有层的改变综合评估,进行病理形态分析。结果溃疡性结肠炎(ulcerative colitis,UC)108例,克罗恩病(Crohn disease,CD)19例,不能排除CD 20例,不能确定为UC或CD 27例,按系统性诊断方法,其中35例不能诊断为IBD。结论按照系统性诊断步骤,IBD不易漏诊,也不会过诊断。内镜活检标本诊断UC较容易,诊断CD较难,除非看到非干酪样上皮样肉芽肿,CD内镜活检的主要目的是排除淋巴瘤和肠结核。     

Mannan-binding lectin (MBL) gene polymorphisms in ulcerative colitis and Crohn's disease

The inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis (UC), are complex multifactorial traits involving both environmental and genetic factors. Mannan-binding lectin (MBL) plays an important role in non-specific immunity and complement activation. Point mutations in codons 52, 54 and 57 of exon 1 of the MBL gene are associated with decreased MBL plasma concentrations and increased susceptibility to various infectious diseases. If these MBL mutations could lead to susceptibility to putative IBD-etiological microbial agents, or could temper the complement-mediated mucosal damage in IBD, MBL could function as the link between certain microbial, immunological and genetic factors in IBD. In this study, we investigated the presence of the codon 52, 54 and 57 mutations of the MBL gene in 431 unrelated IBD patients, 112 affected and 141 unaffected first-degree relatives, and 308 healthy control individuals. In the group of sporadic IBD patients (n = 340), the frequency of the investigated MBL variants was significantly lower in UC patients when compared with CD patients (P = 0.01) and with controls (P = 0.02). These results suggest that MBL mutations which decrease the formation of functional MBL could protect against the clinical development of sporadic UC, but not of CD. This could be explained by the differential T-helper response in both diseases.     

Alternative Medicines as Emerging Therapies for Inflammatory Bowel Diseases

Inflammatory bowel disease (IBD) can be divided into two major categories, ulcerative colitis (UC) and Crohn disease (CD). While the main cause(s) of IBD remain unknown, a number of interventional and preventive strategies have been proposed for use against CD and UC. Many reports have focused on the use of alternative natural medicines as potential therapeutic interventions in IBD patients with minimal side effects. While the use of alternative medicines may be effective in IBD patients that are refractory to corticosteroids or thiopurins, alternative treatment strategies are limited and require extensive clinical testing before being optimized for use in patients.     

Review of Saccharomyces boulardii as a treatment option in IBD

Abstract

Context: Review of the yeast Saccharomyces boulardii as a treatment option for the inflammatory bowel diseases (IBD) ulcerative colitis and Crohn’s disease.

Objective: IBD is caused by an inappropriate immune response to gut microbiota. Treatment options could therefore be prebiotics, probiotics, antibiotics and/or fecal transplant. In this review, we have looked at the evidence for the yeast S. boulardii as a treatment option.

Material and methods: Searches in PubMed and the Cochrane Library with the MeSH words ‘Saccharomyces boulardii AND IBD’, ‘Saccharomyces boulardii AND Inflammatory Bowel Disease’, ‘Saccharomyces boulardii AND ulcerative colitis’ and ‘Saccharomyces boulardii AND Crohn’s disease’ gave total a total of 80 articles. After exclusions because of irrelevance, articles in other languages and some articles that were not available, 16 articles were included in this review.

Results: Three of the clinical trials showed a positive effect of S. boulardii in IBD patients (two Crohn’s disease, one ulcerative colitis), while there was one trial that didn’t prove any effect (Crohn’s disease). Included Animal trials and cell assays describes different anti-inflammatory mechanisms of S. boulardii supporting a possible effect when treating IBD patients.

Discussion: The number of studies of S. boulardii as treatment for IBD is limited. Furthermore, the existing trials have small populations and short duration.

Conclusion: We do not have enough evidence to prove the effect of S. boulardii in IBD. Saccharomyces boulardii is, however, a plausible treatment option in the future, but more placebo-controlled clinical studies on both patients with ulcerative colitis and Crohn’s disease are needed.     

Presence of Anti-proteinase 3 Antineutrophil Cytoplasmic Antibodies (Anti-PR3 ANCA) as Serologic Markers in Inflammatory Bowel Disease

Anti-proteinase 3 anti-neutrophil cytoplasmic antibodies (anti-PR3 ANCA) represent an established serologic marker of active granulomatosis with polyangiitis, but their role as a serologic marker in inflammatory bowel disease (IBD) remains uncertain. This study evaluates the presence of anti-PR3 ANCA and their validity as a serologic marker to aid in the diagnosis of IBD. Retrospectively, 142 serum samples obtained at early stages of the disease were analyzed with a new chemiluminiscent assay for the measurement of anti-PR3 ANCA. The results were correlated to the diagnosis, clinical, and therapeutic data, and ANCA and anti-Saccharomyces cerevisiae antibody (ASCA) measurements available from routine clinical practice. Anti-PR3 ANCA were significantly more prevalent (p?<?0.0001) and their titers significantly higher (p?<?0.0001) among ulcerative colitis compared with Crohn’s disease patients. Receiver operating characteristic curve analysis performed with anti-PR3 ANCA titers to assess the diagnostic accuracy of the assay gave an area under the curve of 0.81 (95 % CI (0.76–0.89); p?<?0.0001), with a cut-off titer of 11.8 chemiluminescent units displaying 52.1 % sensitivity and 97.3 % specificity for ulcerative colitis. Combining anti-PR3 ANCA positivity with IgA ASCA negativity as the diagnostic parameter demonstrated highest diagnostic utility, with a sensitivity and specificity of 47.5 % and 98.2 %, respectively. In our cohort, anti-PR3 ANCA was significantly more prevalent in ulcerative colitis than in Crohn’s disease patients, which suggests a possible role of anti-PR3 ANCA as a serologic marker to aid in the diagnosis of IBD.     

Effect of Trichinella spiralis intervention on TNBS-induced experimental colitis in mice

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease (CD), are chronic autoimmune diseases with a high recurrence rate. Epidemiological data have shown that the incidence of IBD increases annually because of improved sanitary conditions and reduced parasitic infection rates. In this experiment, experimental colitis was induced in mice by administering 2,4,6-trinitrobenzene sulfonic acid (TNBS) 28?days after they were infected with Trichinella spiralis to confirm that T. spiralis infection could alleviate the severity of TNBS-induced colitis.Thirty-six male BALB/c mice aged 6–8 weeks were randomly divided into four groups: control group (with 50% ethanol, Control), T. spiralis-infected group (TS-Control), TNBS-induced colitis model group (Colitis), and T. spiralis-pre-infected and TNBS-induced colitis group (TS-Colitis). The mice were sacrificed 3, 7, and 14?days after the model was established. Changes in various colitis indicators to investigate the effect of T. spiralis infection on TNBS-induced murine CD model.Results showed that the weight, DAI score, and macroscopic and microscopic colon damage in the TS-Colitis significantly decreased compared with those in the Colitis. ELISA revealed that the IFN-γ expression decreased and the IL-4 expression increased in the TS-Colitis compared with those in the Colitis. Western Blotting results revealed that the NF-κB expression increased in the Colitis and higher than those in the TS-Colitis. And Flow cytometry results revealed that the percentage of CD4+CD25+Foxp3+ Treg cells significantly increased in the TS-Colitis.T. spiralis-infected mice induced Th2 immune responses and balanced Th1 immune responses stimulated by TNBS to ameliorate intestinal inflammation.     

细胞因子在炎症性肠病中作用机制的研究进展

炎症性肠病(IBD),包括克罗恩病和溃疡性结肠炎两种类型.它是在多种致病因素共同作用下由肠道免疫调节紊乱引发的炎症性疾病.近年来的研究发现,多种免疫细胞和细胞因子参与了两型IBD的发生和发展,其中ICE、辅助T细胞Th1/Th2在两型IBD中的功能和角色受到重视.对细胞因子在炎症性肠病中作用机制的深入研究为IBD的治疗提供了新的线索.     

Leukocyte traffic control: a novel therapeutic strategy for inflammatory bowel disease – an update

Adhesion molecules play a key role in the pathogenetic mechanisms of inflammatory bowel disease (IBD), both in Crohn’s disease (CD) and ulcerative colitis (UC). In the last decade, some progress has been made in understanding their key role in leukocyte trafficking control in terms of basic research, but evidence of clinical efficacy is lacking. In the last 2 years, new molecules directed against integrins and integrin receptors have been developed and investigated in clinical trials, showing that anti-α4β7 integrin agents can be effective and safe for the induction and maintenance of remission in active CD and UC. Preliminary data show that anti-MAdCAM, anti-β7 and anti-integrin receptor agents are not all effective in IBD. Such results open new perspectives on clinical management of IBD, and new directions in understanding the role of adhesion molecules and leukocyte recruitment both in CD and UC.     

Increased Fecal Levels of Chromogranin A, Chromogranin B, and Secretoneurin in Collagenous Colitis

Interactions between the enteric nervous system and the immune system are suggested to play an important role in the pathophysiology of inflammatory bowel disease (IBD). This study aims to determine if chromogranin A (CgA), chromogranin B (CgB), and secretoneurin (SN) are detectable in feces (F) from patients with collagenous colitis (CC) and to compare the levels found in patients with ulcerative colitis (UC) and Crohn’s disease (CD) before and during treatment. Patients with CC (n = 12) were studied before and after 3, 7, 28, and 56 days of treatment. Patients with IBD (UC, n = 21; CD, n = 11) were studied before and after 28 and 56 days of treatment. Clinical data were recorded, and fecal samples were collected at each occasion. F-CgA, F-CgB, and F-SN were measured by RIA. Eleven patients with CC, 21 with UC, and 10 with CD achieved remission. On inclusion, CC patients had higher levels of F-CgA, F-CgB, and F-SN than patients with IBD and controls. Patients with IBD expressed markedly lower levels of F-SN than controls. During treatment, F-SN in CC patients decreased to control levels but remained low in IBD patients. No change was found in F-CgA or F-CgB in any of the groups. In conclusion, CgA, CgB, and SN are detectable in feces, and CC patients express higher values than patients with IBD and controls. During treatment, F-SN decreased to control levels in CC. These findings suggest that the enteric nervous system is clearly involved in the pathophysiology of CC.     

Met-enkephalins in patients with inflammatory bowel diseases

PurposeOpioid peptides provide a link between the neuroendocrine and immune systems. They modify the inflammatory process through their effect on the synthesis and secretion of cytokines and on the proliferation of leukocytes to the inflammatory lesion. The evaluation analyzed changes in free met-enkephalin concentration values in the serum and colon mucosal biopsy specimens of patients with inflammatory bowel disease (IBD).Material and MethodsIn serum and colon mucosal biopsy specimens, free met-enkephalin levels were determined in 43 patients with ulcerative colitis (UC) and 38 individuals with Crohn's disease (CD). The evaluation analyzed the effect of disease activity, inflammatory lesions of the colon and laboratory parameters, on the level of the investigated marker. The control group consisted of 45 healthy volunteers.ResultsSerum free met-enkephalin levels were depressed in patients with CD (85.4pg/ml) and UC (101.5pg/ml) as compared to the controls (119.4pg/ml). Met-enkephalin levels in colonic biopsies collected from inflammatory lesions in IBD patients were significantly higher as compared to sections without inflammatory lesions (6.59pg/mg vs. 2.89pg/mg, p < 0.01 in the CD group and 6.12pg/mg vs. 3.47pg/mg, p < 0.05 in the UC group) and their level correlated with disease activity.ConclusionsThe present investigation is the first study that demonstrates changes in free met-enkephalin levels in IBD that may play a role in the pathogenesis and course of the disease. Further studies are necessary to assess the anti-inflammatory effect of opioid peptides.     

Treatment of inflammatory bowel disease by chemokine receptor-targeted leukapheresis

Leukapheresis removes circulating leukocytes en route to the target organ. Hitherto unspecific matrixes have been used to remove leukocytes in inflammatory bowel disease (IBD). This report describes a novel selective leukapheresis column based on chemokine–chemokine receptor interaction. We found an increased expression of the gut homing chemokine receptor CCR9 on CD14⁺ monocytes and on CD3⁺ T lymphocytes from IBD patients. Biologically active CCL25 was coupled to a Sepharose matrix and demonstrated to selectively remove CCR9-expressing cells leaving other cell populations largely unaffected. A patient with active ulcerative colitis, was subjected to CCL25-column leukapheresis. Four days after treatment, he experienced clinical improvement and stable disease improvement ensued. The study illustrates that specific cells can be targeted using high affinity interactions, i.e., CCL25–CCR9 interactions to remove pathogenic gut-homing cells. Leukapheresis using the bCCL25 column should be investigated in a clinical phase I trial of patients with inflammatory bowel disease.     

Towards a molecular risk map—Recent advances on the etiology of inflammatory bowel disease

Recent advances have enabled a comprehensive understanding of the genetic architecture of inflammatory bowel disease (IBD) with over 30 identified and replicated disease loci. The pathophysiological consequences of disease gene variants in Crohn disease and ulcerative colitis, the two main subentities of IBD, so far are only understood on the single disease gene level, yet complex network analyses linking the individual risk factors into a molecular risk map are still missing. In this review, we will focus on recent pathways and cellular functions that emerged from the genetic studies (e.g. innate immunity, autophagy) and delineate the existence of shared (e.g. IL23R, IL12B) and unique (e.g. NOD2 for CD) risk factors for the disease subtypes. Ultimately, the defined molecular profiles may identify individuals at risk early in life and may serve as a guidance to administer personalized interventions for causative therapies and/or early targeted prevention strategies. Due to this comparatively advanced level of molecular understanding in the field, IBD may represent precedent also for future developments of individualized genetic medicine in other polygenic disorders in general.     

Gene expression in mononuclear cells from patients with inflammatory bowel disease

OBJECTIVES: Discovery of Nod2 as the inflammatory bowel disease 1 (IBD1) susceptibility gene has brought to light the significance of mononuclear cells in inflammatory bowel disease pathogenesis. The purpose of this study was to examine changes in gene expression in peripheral blood mononuclear cells in patients with untreated Crohn's disease (CD) and ulcerative colitis (UC) as compared to patients with other inflammatory gastrointestinal disorders and to healthy controls. METHODS: We used a 2400 gene cDNA glass slide array (MICROMAX) to examine gene expression in peripheral blood mononuclear cells from seven patients with Crohn's disease, five patients with ulcerative colitis, 10 patients with other inflammatory gastrointestinal disorders, and 22 age- and sex-matched controls. Results. Novel categories of genes differentially expressed in Crohn's disease and ulcerative colitis patients included genes regulating hematopoietic cell differentiation and leukemogenesis, lipid raft-associated signaling, the actin cytoskeleton, and vesicular trafficking. Conclusions: Altered gene expression in mononuclear cells may contribute to inflammatory bowel disease pathogenesis.     

杀菌/通透性增加蛋白基因Glu216Lys多态性与中国汉族人群炎症性肠病无关

 目的：探讨杀菌/通透性增加蛋白（BPI）基因Glu216Lys多态性与中国汉族人群炎症性肠病（IBD）发病及各种临床特征的相关性。方法：纳入286例确诊的汉族IBD患者［173例克罗恩病（CD）和113例溃疡性结肠炎（UC）］及年龄、性别匹配的332名健康人进行病例对照研究。采用引物介导的限制性分析PCR方法检测基因分型;应用单因素分析和Logistic回归模型分析该位点多态性对IBD发病及临床特征的影响。结果：CD和UC病例组与正常对照组间Glu216Lys基因型和等位基因频率差异均无统计学意义（均P>0.05）;进一步分析Glu216Lys与CD和UC的临床特征关系,差异均无统计学意义（P>0.05）。结论：BPI基因 Glu216Lys多态性与中国汉族人群IBD发病和临床特征无明显相关。IBD的遗传易感性具有种族差异性。     

Association between CARD8 rs2043211 Polymorphism and Inflammatory Bowel Disease: A Meta-Analysis

Objective: The aim of this study was to determine whether caspase recruitment domain-containing protein 8 (CARD8) rs2043211 polymorphism was associated with susceptibility to inflammatory bowel disease (IBD).

Methods: Relevant studies were searched using PubMed and Embase up to February 2014. A meta-analysis was conducted on the association between rs2043211 polymorphism and IBD using: (1) allele contrast, (2) the dominant model, (3) the recessive model, and (4) homozygote contrast. The pooled estimated of risk was obtained by random-effects model or fixed-effects model. Publication bias was assessed by Egger’s test.

Results: Eight relevant articles with a total of 10?534 IBD patients [6785 Crohn’s disease (CD), 3713 ulcerative colitis (UC) and 36 indeterminate colitis (IC)] and 6755 healthy controls were included in the meta-analysis, which consisted of 12 studies, 12 for CD, 10 for UC, 2 for IC. There was no significant association between rs2043211 polymorphism and IBD, CD, and IC in overall population. However, stratified meta-analysis by ethnicity showed significant association between rs2043211 polymorphism and CD in the European population under the dominant model [odds ratio (OR)?=?1.210, 95% confidence interval (CI)?=?1.013–1.445, p?=?0.036] and homozygote contrast (OR?=?1.212, 95% CI?=?1.005–1.461, p?=?0.044).

Conclusions: Our meta-analysis results indicated significant association between rs2043211 polymorphism and the susceptibility to CD under the dominant model and homozygote contrast in the European population.     

Clinical predictors of inflammatory bowel disease in a genetically well-defined Caucasian population

Background  

Crohn's disease (CD) and ulcerative colitis (UC), the two main types of inflammatory bowel disease (IBD), are multifactorial conditions of unknown etiology. The objective of this study is to examine the combined gene-environment interactions influencing IBD susceptibility in a well-defined Caucasian cohort in rural mid-America.     

Th17 cells: interactions with predisposing factors in the immunopathogenesis of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic inflammatory state of the GI tract of unknown etiology. Classically, tissue injury in IBD is thought to be primarily mediated by Th1 cells in Crohn’s disease or Th2 cells in ulcerative colitis. The discoveries of new subsets of T-helper cells, especially Th17 cells, have revolutionized our understanding of the disease immunopathology. Th17 cells seem to affect both innate and adaptive immune responses by the release of regulatory cytokines. Understanding the role of Th17 cells in IBD pathogenesis and targeting their regulatory cytokines may provide potential therapeutic approaches for the treatment of IBD in the future.     

Clinical significance of soluble immunoglobulins A and G and their coated bacteria in feces of patients with inflammatory bowel disease

Background

Immunoglobulin A (IgA) and IgG are major components in human intestinal mucosal surface and sera, and IgA- or IgG-coated bacteria play a vital role in the intestinal homeostasis. However, the correlation of IgA, IgG and their coated bacteria with the clinical characteristics of inflammatory bowel disease (IBD) has not been fully clarified.

Methods

The levels of soluble IgA and IgG in sera and feces were detected by ELISA, and the percentage of IgA- and IgG-coated bacteria in feces was analyzed by flow cytometry. Crohn’s disease activity index (CDAI) and Simple Endoscopic Score for Crohn’s disease (SES-CD) for Crohn’s disease (CD) or Mayo score and ulcerative colitis endoscopic index of severity (UCEIS) for ulcerative colitis (UC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to evaluate the disease activity.

Results

178 patients with CD, 75 patients with UC and 41 healthy donors were recruited in this study. We found that the concentrations of soluble IgA and IgG in feces of active IBD patients were significantly higher than those in healthy controls and that the levels of soluble IgA and IgG in feces from IBD patients were positively correlated with CRP, ESR, Mayo score, UCEIS, SES-CD, and CDAI, respectively. Moreover, we also observed that the percentage of IgA- and IgG-coated bacteria markedly increased in feces of IBD patients, especially in CD patients at the age of 17 to 40 years old, with terminal ileal lesions and perianal lesions, as well as from E2 UC patients, and was closely associated with disease activities.

Conclusions

The levels of soluble IgA and IgG and the percentage of IgA- and IgG-coated bacteria strikingly increase in feces of IBD patients and correlate with disease activity.

     

Clinical value of serum eosinophilic cationic protein assessment in children with inflammatory bowel disease

Introduction

Eosinophils contribute to the pathogenesis of inflammatory bowel disease (IBD) in the intestine. Eosinophilic cationic protein (ECP) is one of the most important eosinophilic specific mediators released during activation. The aim of the study was to evaluate the clinical value of serum ECP determination in children with active and inactive IBD and its correlation with disease activity.

Material and methods

There were 125 children with IBD (63 with Crohn''s disease – CD, 44 with ulcerative colitis – UC, 18 indeterminate colitis – IC) enrolled in the study. Among them 83 children were in the active phase of the disease, while the remaining 42 were in remission. The control group consisted of 56 healthy children. The ECP was assessed three times in children with active IBD, at baseline and after 2 and 6 weeks of treatment and once in children with inactive IBD and controls using fluoroenzymeimmunoassays.

Results

We found elevated ECP at baseline in the total active IBD group when compared to the inactive IBD and control groups, decreasing during treatment. Serum ECP was also elevated in the active UC and CD groups when compared to the inactive UC and CD groups, and correlated with clinical UC and CD activity (R = 0.57 and R = 0.52, p < 0.05, respectively) and duration of the clinical manifestation in UC (R = 0.62, p < 0.05) but not with the disease location in the gastrointestinal tract, or endoscopic and histopathological activity.

Conclusions

Evaluation of serum ECP in children with IBD may be useful in disease activity assessment at onset and during the treatment.