(Auto)antibodies in inflammatory bowel diseases

Patients who have inflammatory bowel diseases (IBD) express strong antibody responses to a variety of epitopes. A number of (auto)antibodies have been described in patients who have Crohn's disease or ulcerative colitis. These markers reflect a loss of tolerance toward bacterial and fungal flora and have been studied for their clinical value in IBD patients. However, currently, they have no place in the diagnostic work up. Their real promise may lie in their use as surrogate markers of complicated aggressive disease as shown in various retrospective studies, but prospective data are lacking.     

抗中性粒细胞胞浆抗体在炎性肠病中的意义

目的 研究抗中性粒细胞胞浆抗体（ＡＮＣＡ）在炎性肠病（ＩＢＤ）中的发生率、其针对的靶抗原及其与临床疾病活动性的关系。方法 用间接免疫荧光法对７６例溃疡性结肠炎（ＵＣ）、３６例克隆病（ＣＤ）及２１０例正常者进行ＡＮＣＡ的筛选测定,用ＥＬＩＳＡ检测ＡＮＣＡ针对的不同靶抗原。结果 ７６例ＵＣ患者中血清ＡＮＣＡ阳性者占７１．１％,均为核周型染色,明显高于ＣＤ患者ＡＮＣＡ的阳性率（８．３％,Ｐ〈０．００１）     

Portal vein thrombosis in inflammatory bowel diseases: A single-center case series

Background and methodsPortal vein thrombosis (PVT) has been reported as a complication of IBD in some case reports. We describe the presentation, diagnostic approaches, underlying risks factors and clinical outcome of 8 IBD patients with PVT.Case-seriesThe patients presented with partial PVT (4 patients) or portal cavernoma. Five patients had undergone surgery. In 2 patients portal biliopathy was diagnosed after detection of PVT. In 4 patients, the diagnosis of PVT was made while IBD was in remission.Five patients showed at least one risk factor for hypercoagulability: lupus anti-coagulant (one patient), increased von Willebrand factor (2 patients) or homocysteine levels (4 patients).Four patients received anticoagulant therapy for 6 months. None experienced other thrombotic events during a median of 5 years (range 2–8 years).ConclusionPVT is a potential complication of IBD, usually associated with acquired or inherited risks factors for hypercoagulability and with a benign outcome.     

Cytomegalovirus colitis complicating inflammatory bowel disease

When patients with inflammatory bowel disease (IBD) are admitted to the hospital with a flare of acute severe colitis, the possibility of a concurrent cytomegalovirus (CMV) infection causing or worsening the colitis is often considered. IBD patients are usually immunosuppressed, and therefore presumably at increased risk for active CMV infection and disease. Multiple techniques are used to diagnose CMV infection, including endoscopy, histology, serology, viral culture, CMV antigen testing, and CMV DNA testing. Immunohistochemistry (IHC) performed on colon biopsy specimens with monoclonal antibodies directed against CMV immediate early antigen is considered by most to be the current gold standard for diagnosis. The prevalence of CMV infection in acute severe colitis appears to be 21-34%, and the prevalence of CMV infection in the steroid refractory subgroup of these patients is 33-36%. After antiviral therapy, colitis remission rates in IBD patients with CMV infection range from 67% to 100%, though CMV histological infection or the presence of circulating virus alone is not always associated with steroid resistance, and may not require antiviral therapy.     

Salmonella infections complicating inflammatory bowel disease

One hundred and five of 267 patients with inflammatory bowel disease at a community hospital had recorded diarrhea, but only one had Salmonella (0.9%). Two additional patients, one from another institution, are also reported. A literature review disclosed only 37 cases, 18 of which were adequately defined clinically. Patients with IBD may not be at an increased risk for Salmonella infection. Salmonella infection may increase the severity of IBD, and therefore antibiotics may be necessary.     

Venous thrombosis in inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) have a threefold increased risk of venous thrombosis, a major cause of morbidity and mortality. Although the exact mechanism explaining the initiation of thrombosis remains unclear, it is likely to be a multifactorial process. Reported abnormalities include activation of markers of the coagulation cascade, disturbed fibrinolysis and the activation of platelets. The contribution of thrombophilic disorders such as factor V Leiden, prothrombin gene mutations and hyperhomocysteinaemia are discussed, but their role in thrombosis associated with IBD has remained unclear. Recent research has examined elevated CD40, P-selectin levels and tissue factor-bearing microvesicles in venous thrombosis, and the relevance of these observations to IBD is reviewed.     

Dysplasia in inflammatory bowel diseases

In both Crohn's disease and ulcerative colitis, the secondary prevention of colorectal cancer basically relies on the histological detection of dysplasia. In inflammatory bowel diseases, dysplasia identifies the subgroup of patients eligible for stricter surveillance (or prophylactic colectomy).In clinical practice, a number of issues may influence the benefits of clinico-pathological surveillance for inflammatory bowel disease patients with dysplasia, including: sampling errors, inconsistent biopsy assessments, patients’ compliance with follow-up requirements, and how heath care is organized. Even in such a multifaceted context, it has been demonstrated that dysplasia surveillance is effective in reducing colorectal cancer-related mortality and morbidity.This paper focuses on current issues concerning the histological assessment of inflammatory bowel disease-associated dysplastic lesions.     

Anti-neutrophil cytoplasmic antibodies (ANCA) and inflammatory bowel diseases in Chinese

Inflammatory bowel diseases are uncommon in the Chinese, but the incidence is rising. Their differentiation from infective colitis is often not clear-cut and diagnosing inflammatory bowel diseases can be difficult in Asia. We have studied Chinese patients with ulcerative colitis (N=19) and Crohn's disease (N=12) for anti-neutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISA). Patients with enteric fever (N=29) and irritable bowel syndrome (N=24) were recruited as controls. Seventy-three percent of ulcerative colitis patients exhibited either p-ANCA (31%) or c-ANCA (42%) by IIF. Twenty-five percent of Crohn's disease patients were found to be p-ANCA positive. However, these ANCA were nonreactive to anti- granule, antiproteinase 3, antimyeloperoxidase, or antilactoferrin. All positive patients had extensive colitis. Sera collected from patients suffering from enteric fever and irritable bowel syndrome were negative for ANCA by IIF and ELISA. We concluded that the detection of ANCA is helpful in diagnosing inflammatory bowel diseases. Further attempts to characterize these autoantibodies are needed.This study was partly supported by the Croucher Foundation (grant 1634-29) and Research Grant Committee (grant CUHK/34/92M).     

Antineutrophil cytoplasmic autoantibodies and anti-Saccharomyces cerevisiae antibodies in inflammatory bowel diseases.

BACKGROUND/AIMS: Perinuclear antineutrophil cytoplasmic autoantibody is a marker for ulcerative colitis, and anti-Saccharomyces cerevisiae antibody is known to be associated with Crohn's disease. The purpose of this study was to search the value of detecting perinuclear antineutrophil cytoplasmic autoantibody and anti-Saccharomyces cerevisiae antibody for the diagnosis of Turkish inflammatory bowel disease patients. METHODS: Serum samples were obtained from 80 patients with ulcerative colitis, 61 patients with Crohn's disease and 40 healthy controls. Determination of both anti-Saccharomyces cerevisiae antibody and antineutrophil cytoplasmic autoantibody was performed with the standardized enzyme-linked immunosorbent assay. RESULTS: In cases with ulcerative colitis, 65% tested seropositive for antineutrophil cytoplasmic autoantibody, whereas the controls showed 2.5% positivity. In cases with Crohn's disease, 63.9% tested seropositive for anti-Saccharomyces cerevisiae antibody, whereas the controls showed 2.5% seropositivity. The combination of a positive anti-Saccharomyces cerevisiae antibody test and a negative antineutrophil cytoplasmic autoantibody yielded a sensitivity and specificity of 32.0% and 97.5%, respectively. The combination of a positive perinuclear antineutrophil cytoplasmic autoantibody and a negative anti-Saccharomyces cerevisiae antibody test yielded a sensitivity and specificity of 44.2% and 97.5%, respectively. CONCLUSIONS: Both serologic tests may aid in the differential diagnosis of inflammatory bowel disease.     

Chemokines in inflammatory bowel diseases

Uncontrolled activation of mucosal effector cells has been identified as the main pathogenic mechanism involved in the initiation and perpetuation of mucosal inflammation in inflammatory bowel diseases (IBD). The sustained activation of these cells leads to the aberrant production of various pro-inflammatory mediators, which co-ordinated action amplifies the inflammatory process. In this setting a network of tissue-specific chemoattractant cytokines (chemokines) and their corresponding receptors have been implicated as main contributors in the initiation and perpetuation of the inflammatory reaction in IBD. They are produced by a variety of inflammatory cells present in IBD lesions, as well as endothelial and epithelial cells. Chemokines not only control the multistep process of leukocyte adhesion to and migration across the endothelium, but also the release of lipid mediators and oxygen radicals from leukocytes, the modulation of tumorigenesis, release of matrix metalloproteinases and tissue fibrosis. Numerous data indicate that that intestinal chemokine expression is non-selectively up-regulated in IBD and correlates with disease activity. The development of selective inhibitors for chemokines or chemokine receptors, based on a more complete understanding of the immunopathogenic role of chemokines in intestinal inflammation, will be of great interest as potential novel therapeutic strategies in IBD.     

Endoscopy in inflammatory bowel diseases

A correct diagnosis, adequate assessment of disease activity, avoidance of surgery by endoscopic interventions, and effective cancer surveillance make endoscopy crucial in the management of inflammatory bowel diseases (IBDs). Impressive technical developments of several endoscopic techniques over the past few decades have allowed a detailed visual impression of the affected gut and enable tissue sampling and various therapeutic interventions. Here we propose guidelines for endoscopy in inflammatory bowel disease, and review all currently available endoscopic techniques relevant to the proper treatment of IBD patients.     

Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases

Anti-tumor necrosis factor(TNF) antibodies are successfully used in the therapy of inflammatory bowel diseases(IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNF, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNF antibodies were shown to differ in their mode-of-action in vivo and in vitro. Furthermore, the anti-TNF agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn's disease patients, suggesting different contributions of TNF in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNF agents in general and analyze comparatively different effects of each antiTNF agent such as TNF neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membranebound form of TNF compared to the soluble form for the immunopathogenesis of IBD. Furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with antiTNF antibodies in chronic intestinal inflammation, by predicting response to therapy.     

Mesenteric venous thrombosis in inflammatory bowel disease

Mesenteric venous thrombosis (MVT) is a rare but potentially catastrophic clinical complication, which may lead to ischemia or infarction of the intestine and/or the emergence of portal hypertension. An association between inflammatory bowel disease (IBD) and MVT has previously been described, but clinical factors that may contribute to this complication in the setting of IBD are not well characterized. Diagnosis of MVT in IBD is difficult, as patients frequently present with nonspecific abdominal discomfort, which may delay diagnosis and initiation of treatment. We report 6 of 545 IBD patients at our center (1.1%) that developed MVT, and describe presentation, diagnostic approaches, treatment options, underlying contributing factors, and outcome. The diagnosis was determined with abdominal computed tomography (CT) in 5 of 6 cases. Clinical factors, which were thought to contribute to MVT, included underlying hypercoagulability, low-flow state, uncontrolled inflammation, perioperative time period, and prior surgical manipulation of the portal vein following orthotopic liver transplantation. There were no deaths as a result of MVT, although 1 patient developed severe portal hypertension and another experienced intestinal infarction requiring extensive resection. We conclude that MVT is an important clinical consideration in IBD patients, specifically during the perioperative setting, and diagnosis is facilitated with the use of CT scan.