炎症性肠病临床表型与免疫标记物的相关性

炎症性肠病(IBD)是一种病因不明的慢性肠道疾病,包括克罗恩病(CD)和溃疡性结肠炎(UC)。研究显示,多种免疫标记物与IBD的临床表型密切相关,正确认识这些标记物将有助于IBD的诊断分型、判断疾病活动程度以及预测疾病预后等。本文就免疫标记物与IBD临床表型的关系作一综述。     

Anti-Saccharomyces cerevisiae Antibodies in Inflammatory Bowel Disease: a Family Study

Background: Antibodies to Saccharomyces cerevisiae (ASCA) have been described as specific markers for Crohn disease (CD). The reason for this disease specific generation of antibodies is not clear. Therefore, a family study was performed to evaluate whether the antibody production was due to genetic or environmental factors. Methods: Seventy-one patients with CD, 25 patients with ulcerative colitis (UC), their 282 first-degree relatives, and 32 spouses were included. As controls, 43 sera from healthy persons and 69 sera from patients with various autoimmune disorders were tested for ASCA by indirect immunofluorescence and ELISA. Results: ASCA were detected in 68% of the patients with CD and in none of the controls, UC patients included. Forty-eight (25%) first-degree relatives ofpatients with CD were ASCA-positive. ASCA status of relatives was not related to the fact whether these persons lived in the same household with the patients or not. However, one of the spouses of CD patients (4%) was found to be ASCA-positive and the antibody was also found in 5 (6%) ofthe relatives of UC patients. Conclusions: ASCA are specific markers for CD. Since these antibodies are found in 25% of first-degree relatives, the generation of ASCA may be mainly related to genetic influences although environmental factors may also play a certain role.     

Musculoskeletal Manifestations in a Population-based Cohort of Inflammatory Bowel Disease Patients

Background: Musculoskeletal disorders are the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). Wide ranges of prevalence have been reported depending on the criteria used to define spondylarthropathy and on the selection of patients. We aimed to evaluate the prevalence and clinical spectrum of musculoskeletal manifestations in an inception cohort of European IBD patients. Methods: From 1 October 1991 to 30 September 1993, 202 IBD patients were diagnosed in three centres of two countries (Italy and The Netherlands) by means of a population-based inception cohort study. Of this group of patients, 160 (79%) were interviewed and examined by a rheumatologist and a gastroenterologist in the period June-September 1996. A total of 139/160 patients had an anteroposterior radiograph of the pelvis, and in 140/160 HLA-B27 was determined. Results: 53 (33.1%) of the 160 patients had experienced at least one musculoskeletal manifestation, 29 (18.1%) satisfied the European Spondylarthropathy Study Group (ESSG) criteria for spondylarthropathy and 5 (3.1%) satisfied the modified New York criteria for ankylosing spondylitis. However, 23 (14.4%) patients developed one or more spondylarthropathy-related manifestations without fulfilling any of the classification criteria. In patients satisfying ESSG criteria a significantly higher frequency of women ( P = 0.03), of ocular and liver involvement ( P = 0.01 and P = 0.03, respectively), and use of immunosuppressive drugs ( P = 0.02) was observed. Conclusion: Our study shows a high prevalence of musculoskeletal manifestations in an inception cohort of IBD patients. The clinical spectrum is broader than that defined by spondylarthropathy criteria.     

Increased Serum Levels of Eotaxin in Patients with Inflammatory Bowel Disease

Background: The CC-chemokines eotaxin and eotaxin-2, produced by epithelial and phagocytic cells, are potent and selective chemoattractants for eosinophils and basophils. The eosinophil is a potent inflammatory cell thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD). In this study we investigated the serum concentrations of eotaxin and eotaxin-2 in patients with Crohn disease and ulcerative colitis. Methods: Thirty-one patients with Crohn disease, 35 patients with ulcerative colitis and 41 control patients were studied. Eotaxin and eotaxin-2 serum levels were measured with solid phase sandwich enzyme-linked immunosorbent assays. Results:     

Staphylococcus aureus in Inflammatory Bowel Disease

Background: The potential role of superantigens in inflammatory bowel disease (IBD), particularly Crohn disease, has been broached in studies of the functions of T cell receptors. Staphylococcal cells have been found in intestinal lymph follicles of IBDs. To clarify a role of staphylococcal superantigens in IBD, we attempted to determine whether Staphylococcus aureus could be detected in intestinal mucosa, including surgical specimens and lymph follicles of initial cases. Methods: One-hundred-and-six colonic and ileal specimens were obtained from 38 Crohn disease, 25 ulcerative colitis and 36 non-IBD patients through therapeutic surgery or endoscopic biopsy. In Crohn disease, 23 surgical specimens and 11 biopsy specimens from initial cases were included. DNA was extracted with phenol-chloroform after homogenization and proteinase K treatment in 73 mucosal specimens. Using an inverted microscope, lymph follicle tissue was microdissected from the remaining 33, mostly biopsy, specimens. DNA was then extracted by freeze-thawing. A coagulase gene characteristic of S. aureus was sought. A nested polymerase chain reaction was performed utilizing primers that amplify a region of the coagulase gene. Polymerase chain reaction products were analyzed with polyacrylamide gel electrophoresis. Results: Only one surgically resected colonic specimen, from a 42-year-old male ulcerative colitis patient, registered positive staphylocoagulase amplification. Conclusions: Staphylococcal superantigens are not involved in either the early lesions or the established lesions of Crohn disease. However, S. aureus infection occasionally may occur during the course of IBD.     

炎症性肠病患者外周血淋巴细胞功能相关抗原-1的表达与临床特征的关系

背景：淋巴细胞功能相关抗原-1（LFA-1）是B2整合素家族成员,广泛表达于几乎所有白细胞中。LFA-1／ICAM-1共刺激分子在炎症性肠病（IBD）的发生中发挥重要作用。目的：研究IBD患者外周血LFA-1的表达变化,分析其与患者临床特征的相关性。方法：纳入20名健康体检者和93例IBD患者（其中CD66例,UC27例）,流式细胞术检测外周血CD4＋细胞和外周血单个核细胞（PBMC）中LFA-1的平均荧光强度（MF1）,并分析其与疾病活动度、疾病部位、疾病行为和临床指标的相关性。结果：CD和UC患者PBMC中LFA-1的MFI均显著低于健康对照组（P〈0．05）。CD和UC患者缓解期外周血CD4＋细胞和PBMC中LFA-1的MFI与活动期无明显差异。空回肠型CD患者外周血CIM’细胞和PBMC中LFA-1的MFI较回肠型、结肠型、上消化道型CD患者明显升高（P〈0．05）;狭窄型CD患者外周血CD4＋细胞中LFA-1的MFI显著高于非狭窄非穿透型CD患者（P〈0．05）;有2种肛周病变的CD患者外周血CD4＋细胞和PBMC中LFA-1的MFI显著高于有1种肛周病变者（P〈0．05）。ESR、血清CRP与CDAI评分、Mayo评分呈正相关（P〈0．05）;HCT、Hb、血清ALB与CDAI评分、Mayo评分呈负相关（P〈0．05）。结论：LFA．1参与IBD的发病过程,与CD疾病行为的关系尤为密切,但用于判断疾病活动度尚需进一步研究。     

C反应蛋白反映炎症性肠病的活动性

背景：临床上评估炎症性肠病活动性的方法有临床活动度、C反应蛋白（CRP）和血沉等，三者常不一致。目的：探讨CRP评估炎症性肠病活动性的价值。方法：以Logistic回归法分析80例克罗恩病（CD）、70例溃疡性结肠炎（UC）患者血清CRP与血沉、临床活动度、内镜表现活动性、组织学活动性、低白蛋白血症、贫血、白细胞升高的关系；比较临床严重度、病变部位和药物治疗对CRP的影响。结果：CD中CRP与血沉相关；UC中CRP与血沉、外周血白细胞升高相关。CRP在活动性CD中显著升高（P〈0．01），重度CD和结肠CD中CRP升高较其他各组明显（P〈0．05）；活动性UC中CRP亦显著升高（P〈0．01），重度组中CRP升高较其他组明显（P〈0．05）。药物有效控制临床表现时．CRP显著下降（P〈0．01），复发时重新升高（P〉0．05）。结论：CRP升高更适于反映中至重度结肠CD和UC的活动性：具有快速反映药物治疗有效性的特点。     

炎症性肠病的鉴别诊断

近年来我国炎症性肠病的发病率和患病率均呈上升趋势．作为临床难点的鉴别诊断问题日益引起临床医师的高度重视。本文对炎症性肠病与感染性结肠炎和非感染性结肠炎的鉴别诊断进行阐述．强调应对慢性腹泻、腹痛患者进行及时准确的诊断和鉴别诊断,以最大程度地降低临床漏诊率和误诊率。     

血清分子标记物和易感基因对炎症性肠病鉴别诊断的研究进展

炎症性肠病(IBD)包括克罗恩病(CD)和溃疡性结肠炎(UC),目前两者的鉴别诊断依赖临床症状、内镜检查、病理活检以及实验室和影像学检查等。近年来,IBD相关的生物标记物检测因无创、操作简单、易被患者接受而发展迅速。此外,随着全基因组关联分析(GWAS)的开展,对CD和UC相关遗传突变位点和易感基因的研究取得了较大进展,为疾病诊断提供了新方向。本文就血清分子标记物和易感基因对IBD鉴别诊断的研究进展作一综述。     

英夫利昔单抗治疗炎症性肠病的研究进展

肿瘤坏死因子－α（TNF－α）是一种促炎细胞因子,在炎症性肠病（IBD）的发病过程中起重要作用。英夫利昔,单抗（infliximab）是一种人-鼠嵌合型TNF-αIgGl单克隆抗体,与体内多种形式的TNF-α有较强结合能力。美国食品药品管理局（FDA）于1998年批准该制剂用于治疗传统药物治疗无效的中重度或合并瘘管的克罗恩病（CD）,试验显示其对难治性活动性溃疡性结肠炎（UC）亦有一定疗效。英夫利昔单抗的使用已积累了10年的经验,本文对其作用机制、疗效、安全性方面的研究进展作一综述。     

炎症性肠病基础研究进展——与临床的联系

炎症性肠病（IBD）包括溃疡性结肠炎（UC）和克罗恩病（CD）,是一组反复发作的非特异性慢性肠道炎症性疾病,其病因尚未完全阐明。近年来随着基因组学、免疫遗传学、分子生物学等的发展以及DNA重组动物模型技术的日趋成熟,IBD病因学和发病机制的研究进展迅猛．取得了巨大的成绩。IBD易感基因的发现,驱动了肠道共生菌与肠上皮屏障相互作用致肠黏膜免疫失衡以及天然性免疫与适应性免疫的相互作用等多方面的进展,对IBD发病机制和疾病本质的揭示起到了重要作用。     

炎症性肠病治疗中的新概念

炎症性肠病（IBD）主要包括溃疡性结肠炎（UC）和克罗恩病（CD）,其治疗疗程长、效果不佳、容易反复,主要原因为目前对该病的发病机制仍不甚了解以及缺乏特异性治疗药物。随着对IBD发病机制认识的不断深入,其发病过程中的炎症和免疫途径不断被揭示,这些新理念的发展直接导致了新的治疗药物和治疗方法的出现。本文主要结合目前IBD发病机制的研究进展,对其治疗中的一些新概念作一论述。     

Disease Outcome in Inflammatory Bowel Disease: Mortality,Morbidity and Therapeutic Management of a 796-Person Inception Cohort in the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD)

Background: The course of inflammatory bowel diseases (IBD) has mainly been studied using different methods in single patient cohorts. The aim of the present study was to assess clinical aspects of disease outcome in a population-based cohort of IBD patients over a 4-year period in multiple centres across Europe. Methods: A total of 796 patients with IBD diagnosed in 10 centres between October 1991 and October 1993, registered at the EC IBD study centre (98% of the original cohort), participated in the study. Investigators filled out a standard follow-up form containing questions on the method of follow-up, vital status of the patient, change in diagnosis, extraintestinal manifestations, medical and surgical treatment, and physician's global assessment of disease activity. Results: Complete relief of the complaints was reported in 255 (48%) patients with ulcerative colitis (UC), 9 (50%) with indeterminate colitis (IC), but only in 87 (35%) of patients with Crohn disease (CD). Improvement was reported in 195 (37%) patients with UC, 113 (45%) with CD and 6 (33%) with IC. During the 4-year follow-up period, 23 patients died (14 UC, 8 CD, and 1 IC). The mean age at death was 69.3 years (s, 14.9 years). The deaths of three patients were recorded as directly due to IBD. Conclusions: With the present approach to therapeutic management the short-term outcome of patients with IBD seems to be favourable in 10 medical centres in the north and south of Europe. However, more detailed studies including both objective and subjective measures are necessary.     

Siblings and the Risk of Inflammatory Bowel Disease

Background: Environmental exposures in early life have been implicated in the aetiology of inflammatory bowel disease (IBD). Siblings are used as proxy markers to characterize patterns of exposure relevant to the risk of IBD. Methods: Some 15,823 patients with ulcerative colitis and 12,668 with Crohn disease from the Swedish In-patient Register were compared with 79,546 and 63,035 controls, respectively, in a case-control study. Multiple logistic regression was used to investigate associations with older and younger siblings, and adjustment was made for sex, year of birth, mother's age, region and, additionally, father's social class. Results: Older siblings are associated with a graded increased risk for ulcerative colitis ( P for trend <0.001) and an adjusted odds ratio of 1.15 (95% CI 1.07-1.24) for three or more older siblings. Younger siblings are associated with a graded decreased risk for Crohn disease ( P for trend <0.001) with an adjusted odds ratio of 0.83 (0.76-0.90) for three or more younger siblings. The greatest protective association with Crohn disease was seen for younger siblings born within 2 years of the subject. Older maternal age is independently associated with a decreased risk of Crohn disease, with P for trend <0.001. Additional adjustment for social class did not substantially alter the results. Conclusions: Having siblings is associated with the risk and phenotype of developing IBD, possibly through their influence on patterns of antigenic exposure in early life. The association of maternal age with Crohn disease may reflect age-related changes in maternal immune profile.     

炎症性肠病流行病学研究进展

炎症性肠病(IBD)在不同地区、种族人群中的发病率有显著差异。近年来,IBD在既往高发病率的西方国家趋于稳定,而在亚洲国家呈逐渐增加趋势。IBD发病率在发展中国家逐年增高,可能与发展中国家经济高速发展、工业化进程加速有关,提示环境因素在IBD病因中扮演重要角色。目前国内关于IBD流行病学的研究处于起步阶段,有待联合更多医学中心进行以人群为基础的IBD流行病学研究。     

肠道菌群在炎症性肠病发生中的作用

炎症性肠病（IBD）是一种慢性非特异性肠道炎症性疾病．其明确病因和发病机制至今仍不清楚。近年来随着微生态学的发展．肠道菌群与IBD发病的关系日益受到关注。多项证据表明IBD患者存在肠道菌群紊乱。本文就肠道菌群在IBD发生中作用的研究进展作一综述。     

糖皮质激素治疗炎症性肠病的相关问题

目前炎症性肠病（IBD）的发病机制尚未完全明确,各种治疗方法虽各有利弊,但均未能达到彻底治愈的理想效果。糖皮质激素（GC）是治疗中-重度和暴发性IBD的有效药物,但不能长期维持炎症缓解,且耐药和毒副作用使GC在临床上的应用受到限制。本文就GC治疗IBD的作用机制、GC耐药、GC制剂布地奈德的应用等作-综述。     

炎症性肠病动物模型研究进展

炎症性肠病（IBD）包括溃疡性结肠炎（UC）和克罗恩病（CD）。目前IBD的确切病因和发病机制尚不清楚。相当一部分IBD的研究成果源于动物模型的研究,因此建立合适的动物模型至关重要。本文就几种常用的IBD实验动物模型作一综述。     

炎症性肠病生物药物治疗现状和前景

炎症性肠病(IBD)包括溃疡性结肠炎(UC)和克罗恩病(CD),是一种病因不明的慢性非特异性炎性病变。随着免疫学和生物学的发展,越来越多的生物制剂用于IBD的治疗,这是其药物治疗的发展方向。本文就IBD生物药物治疗现状和前景作一简要综述。     

炎症性肠病患者血浆Frat1水平及其临床意义

进展期T细胞淋巴瘤常见重排蛋白1（Frat 1）作为Wnt信号转导通路的激活蛋白在胚胎发育、肿瘤发生等过程中发挥作用,而Wnt信号通路异常与炎症性肠病（IBD）的发病相关.目的：探讨活动性IBD患者血浆Frat 1水平及其临床意义.方法：纳入2009年6月-2010年5月上海华东医院42例克罗恩病（CD）患者、55例溃疡性结肠炎（UC）患者和56名正常对照者,应用酶联免疫吸附测定（ELISA）检测血浆Frat 1水平,以受试者工作特征（ROC）曲线分析血浆Frat 1水平对IBD的诊断价值,应用Pearson相关分析研究血浆Frat 1水平与临床疾病活动性的相关性.结果：UC患者血浆Frat 1水平显著低于正常对照组（6.55 pg/ml对17.81 pg/m1,P〈0.001）,CD患者血浆Frat 1水平与正常对照组相比差异无统计学意义（P=0.8995）.ROC曲线分析表明血浆Frat 1水平对鉴别UC患者和正常对照者无意义（P=0.2736）.UC患者血浆Frat 1水平与红细胞沉降率（P=0.5994）,C反应蛋白（P=0.4685）和Mayo评分（P=0.3663）之间均无相关性.结论：UC患者血浆Frat 1水平降低,可能与UC的发生存在潜在的联系.