抗酿酒酵母抗体和抗中性粒细胞胞质抗体对炎症性肠病的诊断价值

目的 了解抗酿酒酵母抗体(ASCA)和核周型抗中性粒细胞胞质抗体(pANCA)的分布,观察其在炎症性肠病(IBD)诊断及鉴别诊断中的意义.方法 选择2002年9月至2007年7月在北京协和医院就诊并行ASCA、pANCA检查的IBD患者175例,其中克罗恩病(CD)62例、溃疡性结肠炎(UC)97例、未定型16例.另取对照者167例.采用酶联免疫吸附法测定血清ASCA水平,间接免疫荧光法测定血清pANCA水平.结果 在CD、UC、未定型者、对照者中,ASCA的阳性率分别为45.2%、14.4%、11/16、29.3%,pANCA的阳性率分别为4.8%、56.7 0A、1/16、4.8%.对照者中,ASCA在恶性肿瘤、嗜酸性粒细胞增多症、自身免疫性肝病、弥漫性结缔组织病及肠结核中的阳性率较高(分别为42.1%、2/5、4/10、4/19、4/14).ASCA诊断CD的敏感性、特异性及阳性预测值分别为45.2%、85.6%、66.7%.pANCA诊断UC的敏感性、特异性及阳性预测值分别为56.7%、95.2%、94.8%.联合检测ASCA+/pANCA-诊断CD的敏感性、特异性及阳性预测值分别为41.9%、93.8%,81.3%.联合检测ASCA-/pANCA+诊断UC的敏感性、特异性和阳性预测值分别为48.5%、98.4%、97.9%.结论 ASCA和pANCA不适于作为IBD筛查指标,联合检测有利于UC与CD的鉴别诊断.     

炎症性肠病患者血清中自身抗体检测的临床意义

目的研究抗酿酒酵母抗体(ASCA)和抗中性粒细胞胞浆抗体(pANCA)在炎症性肠病诊断与鉴别诊断中的意义。方法间接免疫荧光生物薄片法检测29例溃疡性结肠炎(UC)、34例克罗恩病(CD)及25例正常对照者血清中ASCA和pANCA的表达。结果pANCA在CD组、UC组和正常对照组中的阳性率分别为47.1%、69.0%和16.0%,UC组显著高于CD组(P<0.05)和正常对照组(P<0.05)。ASCA在上述3组中的阳性率分别为11.8%、58.6%和8.0%,UC组亦显著高于CD组(P<0.05)和正常对照组(P<0.05)。ASCA /pANCA-诊断CD的敏感性、特异性、阳性预测值分别是0、89.7%和0;pANCA /ASCA-诊断UC的敏感性、特异性和阳性预测值分别是20.7%、64.7%和33.3%。结论ASCA和pANCA阳性有利于炎症性肠病的诊断却不能敏感地筛选患者;ASCA和pANCA联合检测不能作为汉族UC和CD鉴别诊断的指标。     

Partial overlap of anti-mycobacterial, and anti- Saccharomyces cerevisiae mannan antibodies in Crohn＇s disease

AIM： To test whether humoral immune reaction against mycobacteria may play a role in anti- Saccharomyces cerevisiae antibodies （ASCA） generation in Crohn＇s disease （CD） and/or whether it correlates with clinical subtypes.
METHODS： The dominant ASCA epitope was detected by Galanthus nivalis lectin （GNL）-binding assay. ASCA and IgG against mycobacterial lysates （M avium, M smegmatis, M chelonae, M bovis BCG M avium ssp. paratuberculosis （MAP）] or purified lipoarabinomannans （LAM） were detected by ELISA. ASCA and anti-mycobacterial antibodies were affinity purified to assess cross-reactivities. Anti-mycobacterial IgG were induced by BCG-infection of mice.
RESULTS： GNL bound to different extents to mycobacterial lysates, abundantly to purified mannosecapped （Man） LAM from M tuberculosis, but not to uncapped LAM from M srnegrnatis. Fifteen to 45% of CD patients but only 0%-6% of controls were seropositive against different mycobacterial antigens. Anti-mycobacterial IgG correlated with ASCA （r = 0.37-0.64; P = 0.003-P 〈 0.001）. ASCA-positivity and deficiency for mannan-binding lectin synergistically associated with anti-mycobacterial IgG. In some patients, anti-mycobacterial antibodies represent crossreactive ASCA. Vice-versa, the predominant fraction of ASCA did not cross-react with mycobacteria. Finally, fistulizing disease associated with antibodies against M avium, M smegmatis and MAP （P = 0.024, 0.004 and 0.045, respectively）.
CONCLUSION： Similar to ASCA, seroreactivity against mycobacteria may define CD patients with complicated disease and a predisposition for immune responses against ubiquitous antigens. While in some patients anti-mycobacterial antibodies strongly cross-react with yeast mannan; these cross-reactive antibodies only represent a minor fraction of total ASCA. Thus, mycobacterial infection unlikely plays a role in ASCA induction.     

Clinical presentation of Crohn's disease. association between familial disease, smoking, disease phenotype, extraintestinal manifestations and need for surgery

BACKGROUND/AIMS: Recent molecular data suggest that genetic factors may underlie the disease heterogeneity observed in Crohn's disease (CD). It was also suggested that familial inflammatory bowel disease (IBD) is a homogenous subgroup, phenotypically different from sporadic disease. Our aim was to determine the clinical presentation in a large CD population. METHODOLOGY: 564 CD patients (m/f: 278/286, age: 37.4 (SD 12.7) yrs, duration: 8.4 (7.1) yrs) were included. Disease phenotype was determined according to Vienna classification. Familial disease, extraintestinal manifestations (EIM), need for surgery and smoking habits were also analyzed. RESULTS: Familial IBD was present in 73 (12.9%) patients. Age at onset and presence of EIMs was associated with familial disease. Penetrating (44.6% vs. <10 yrs: 29.1%, P<0.0001) and ileocolonic disease (54.4% vs. 42.8%, P=0.03) were more common in patients with a disease duration of > or =10 yrs. In a logistic regression model female gender, colonic/ileocolonic location, smoking and familial IBD were independent risk factors for EIMs, while ileal and non-inflammatory disease increased the risk for resections. Smoking was also associated with frequent relapses. CONCLUSIONS: Familial IBD was associated with the presence of EIMs, while ileal involvement and noninflammatory behavior independently increased the risk for surgery. Since penetrating and extensive disease was more frequent in patients with longer disease duration our data support a possible change in location and behavior during the course of disease.     

Lack of association between smoking and Crohn's disease but the usual association with ulcerative colitis in Jewish patients in Israel: a multicenter study

OBJECTIVE: The association between smoking and inflammatory bowel disease (IBD) is well established, but data in Jewish patients in Israel were discrepant. The aim of this study was to examine the smoking habits of Jewish IBD patients in Israel in a large scale, multicenter study. METHODS: Patients with established IBD aged 18-70 yr were interviewed in relation to smoking and other habits. Two controls (one clinic and one neighborhood control matched by age, sex, community group, and education) were sought for each subject. RESULTS: A total of 534 patients (273 ulcerative colitis [UC], and 261 Crohn's disease [CD]), along with 478 clinic controls and 430 neighborhood controls, were interviewed. There was no significant difference in the smoking habits between CD patients and their controls. Of patients with CD, 24.5% were current smokers, as compared to 19.9% of clinic controls and 25.2% of neighborhood controls (NS).The odds ratio for CD in current smokers was 1.30 (95% confidence interval 0.85-1.99) versus clinic controls, and 0.96 (0.63-1.46) versus neighborhood controls. There were also no significant differences in the proportion of ex-smokers between the groups. Only 12.9% of UC patients were current smokers versus 21.9. % Clinic controls, and 26.4% community controls (p<0.005). The proportions of ex-smokers were higher in UC patients 29.7% versus 25.9%, and 19.5% in their respective controls (p<0.001 vs. community controls). No significant differences were found in the proportions of never-smokers between IBD patients and controls. All the above trends were similar in four different parts of the country. The proportion of current smokers in UC decreased with the extent of disease (19.7% in proctitis, 13.6% in left-sided, and 4.5% in total colitis) (p<0.05). Patients with UC were more likely to be light smokers(1-10 cigarettes/day), whereas patients with CD were more likely to be moderate smokers (11-20 cigarettes/day) in comparison to their controls. CONCLUSIONS: The lack of association between smoking and CD has now been established in Jewish patients in Israel. The association was found in UC. The stronger genetic tendency in CD may contribute to this discrepancy.     

Association of perinuclear antineutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies with Vienna classification subtypes of Crohn's disease

BACKGROUND: The Vienna classification of Crohn's disease (CD) subdivides patients according to their age at diagnosis (A), disease location (L), and disease behavior (B).AIM The aim of this study was to test whether perinuclear antineutrophil cytoplasmic antibodies (pANCAs) or anti-Saccharomyces cerevisiae antibodies (ASCAs) correlate to subtypes of CD according to this classification. METHODS: pANCA, ASCA-immunoglobulin (Ig) A, and ASCA-IgG were detected by indirect immunofluorescence in 120 sera of patients with CD and compared with their Vienna classification. RESULTS: Patients with diagnosis of CD at an age of 40 years or older (A2) were more frequently pANCA-positive than those whose disease started at a younger age (A1) (19% vs. 5%, p < 0.05). pANCA-positive patients almost exclusively belonged to the nonpenetrating disease groups (B1 and B2); only one patient had penetrating disease (B3) (B3 vs. non-B3: p = 0.02). There was a cluster of pANCA-positive patients within the A1 B2 L3 subgroup (B2: stricturing disease; L3: ileocolonic involvement). Only 7.5% of ASCA-IgA-positive patients presented with CD that was limited to the colon (L2). ASCA-IgA and ASCA-IgG were more frequently found in patients with upper gastrointestinal disease (L4) (ASCA-IgA: 66.7% vs. 31.5% in non-L4, p < 0.05; ASCA-IgG: 44.4% vs. 27.9%, p < 0.05). CONCLUSION: pANCA and ASCA may be useful in predicting subtypes of CD. They therefore may be helpful in developing subtype-specific disease management strategies.     

Oral contraceptive use and cigarette smoking in Crohn's disease

Previous studies have consistently found strong positive associations between smoking and Crohn's disease. The association between oral contraceptive use and Crohn's disease remains, however, controversial. In order to analyze whether smoking and oral contraceptive use are independent risk factors a case-control study was performed. In 90 women with Crohn's disease and 90 community controls information was assessed about their smoking habits and their use of oral contraceptives. Smoking and oral contraceptive use were associated with one another. After adjusting for oral contraceptive use, the relative risk for smokers compared with nonsmokers was 3.0 (1.3–6.8). After controlling for smoking, the relative risk estimates for oral contraceptive use were for no use, 1–3 years, and >3 years of use 1.0, 2.5 (1.0–6.6), and 4.3 (1.3–14.4), respectively. When oral contraceptive use was stratified by smoking habits, the data show that oral contraceptives only increased the risk for Crohn's disease in nonsmokers. From the lack of increase in risk for combined exposure, it is concluded that both factors might act through a common mechanism.     

Familial expression of anti-Saccharomyces cerevisiae Mannan antibodies in Crohn's disease and ulcerative colitis: a GISC study

OBJECTIVES: Recent studies in familial Crohn's disease (CD) have suggested that anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) may represent a new specific marker of genetic susceptibility. In this study we aimed to assess the importance of ASCAs by comparing their presence in a large number of patients with sporadic and familial occurrence of CD or ulcerative colitis (UC) and their unaffected relatives. METHODS: Serum samples from 96 patients with sporadic CD, 97 patients with sporadic UC, and 50 unrelated healthy controls were tested for ASCAs by a standard ELISA method. Moreover, 73 families with two or more members affected by CD and/or UC were recruited. From these families 58 CD patients, 84 UC patients, and 216 unaffected first degree relatives were investigated. RESULTS: ASCAs were detected in 34 of 96 patients with sporadic CD (35%, p < 0.01 vs controls), 11 of 97 patients with sporadic UC (12%), and two of 50 controls (4%). ASCAs were significantly (p < 0.04) more frequent in patients with familial CD (55%) and familial UC (25%) than in sporadic cases. Moreover, ASCAs were found in 25% of unaffected relatives, and this rate did not significantly differ in CD, UC, and mixed families (28%, 26%, and 22%, respectively). CONCLUSIONS: In this study we confirm that ASCAs occur particularly frequently in CD patients, especially with the presence of a positive family history. However, they are also significantly increased in UC patients with a family history and in a considerable number of unaffected relatives of inflammatory bowel disease families, irrespective of the characteristics of their families (UC, CD, mixed, ASCA positive, and ASCA negative). The presence of ASCAs in unaffected relatives might point toward a genetic predisposition to either CD or UC.     

Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in affected and unaffected relatives of patients with Crohn's disease

BACKGROUND: Crohn's disease is a familial disorder, and antiglycan antibodies to the cell wall mannan of Saccharomyces cerevisiae (ASCA) are highly correlated with Crohn's disease. AIMS: To determine whether there is a familial pattern for expression of serum levels of anti-mannan Ig, and whether this trait is expressed in clinically unaffected Crohn's disease family members. METHODS: 349 patients with Crohn's disease, 87 Crohn's disease affected relatives, 333 inflammatory bowel disease (IBD) free relatives, 58 spouses, and 190 healthy control patients were studied. Serum IgG and IgA binding activity to S cerevisiae cell wall mannan was quantitated by ELISA. RESULTS: A high percentage of patients with Crohn's disease (51.9%) and affected family members (56.3%) were seropositive for anti-mannan Ig, compared with the normal control population (3.7%). Seropositive and seronegative phenotypes of Crohn's disease probands were correlated among all affected relatives, and this association was stronger in affected first degree relatives. Statistical intraclass correlations of quantitative anti-mannan Ig levels revealed significantly less variation within, rather than between families. A significant familial aggregation was observed for affected relatives; this was even stronger for unaffected relatives. While a significant familial aggregation was observed among unaffected siblings pairs, there was no significant correlation among marital pairs. CONCLUSION: Results show that anti-mannan Ig in family members affected and unaffected with Crohn's disease is a familial trait for both affected and unaffected relatives. The lack of concordance in marital pairs indicates that familiality is due in part to a genetic factor or childhood environmental exposure.     

Serum antibodies to Mycobacterium avium subspecies paratuberculosis combined with anti-Saccharomyces cerevisiae antibodies in Crohn's disease patients: prevalence and diagnostic role

Background  

Because Mycobacterium avium subspecies paratuberculosis (MAP), the etiologic agent of Johne’s disease in ruminant, has been identified in the mucosal layer and deeper bowel wall in CD patients, the seroactivity against MAP may define a distinct subset of patients requiring individual treatment. The aim of this study was to assess the performance of anti-MAP antibodies in the diagnostic strategy for CD.     

Recurrent myopericarditis in association with Crohn's disease

Myopericarditis is a rare extraintestinal complication of inflammatory bowel disease (IBD). It has also been described as a side-effect of the treatment of IBD. We report a 37-year-old-woman with Crohn's disease who had several mild episodes of myopericarditis, two of which were associated with a pleural effusion, and two with conduction abnormalities in the atrioventricular node. During the last episode, a nodal rhythm was followed by a third-degree atrioventricular block and a prolonged pause, resulting in loss of consciousness and convulsions. A permanent pacemaker was implanted. Our patient is also human lymphocyte antigen (HLA) B27-positive. HLA B27 is known to be associated with conduction disturbances in the AV node. Recurrent myopericarditis can be a sign of IBD.     

Sjogren's syndrome in association with Crohn's disease

SUMMARY: Crohn's disease has many autoimmune extraintestinal manifestations, such as arthritis, polymyositis, and erythema nodosum. However, an association between Crohn's disease and Sjogren's syndrome, an autoimmune disease, has rarely been reported. We describe the fourth case of Sjogren's syndrome in association with Crohn's disease. The patient is a 43-year-old African-American female diagnosed with Crohn's disease in 1981. Twenty years later, she developed abdominal pain, arthralgias, and sicca symptoms. Further evaluation led to a diagnosis of Sjogren's syndrome. Sjogren's syndrome should be considered in patients with underlying Crohn's disease who develop a constellation of constitutional, joint, and sicca symptoms.     

Helping patients with Crohn's disease quit smoking

Smoking is not only a risk factor for Crohn's disease, but ongoing smoking is associated with a poorer disease course. Therefore, smoking cessation should be an important treatment strategy for Crohn's disease patients who smoke tobacco. Recent improvements in understanding how people quit smoking and the development of pharmacological interventions, such as nicotine patches and bupropion, have improved cessation rates. In this article, we first briefly review the evidence supporting the adverse effects of smoking on the disease course. We next review the current understanding of how people change addictive behaviors, such as smoking. We then describe how the gastroenterologist can aid the patient with Crohn's disease to quit smoking, including appropriate and brief counseling strategies and the use of adjunctive treatments. Given the improvements in smoking cessation strategies, all patients with Crohn's disease should be strongly advised to quit smoking and be aided in doing so.     

Anti-Saccharomyces cerevisiae antibodies in coeliac disease

OBJECTIVE: To evaluate, retrospectively, the frequency of anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with coeliac disease. MATERIAL AND METHODS: ASCA, IgG and IgA were determined by ELISA in sera of 238 coeliac patients. The patients were divided into three groups: group I - 125 untreated patients; group II - 42 patients under a strict gluten-free diet (GFD); and group III - 71 patients who did not comply with a GFD. Sera of 80 healthy blood donors served as controls. RESULTS: The frequency of ASCA (IgG or IgA) was significantly higher in untreated coeliac patients than in the control group (27.2% versus 3.7%, p=10(-5)). In 238 coeliac patients, the frequency of ASCA was significantly higher in adults than in children (35.4% versus 21.1%, p=0.01). In group III, the frequency of ASCA was significantly higher in adults than in children (60% versus 26.1%, p=0.004). In 238 coeliac patients, ASCA IgG were significantly more frequent than ASCA IgA in both children (19% versus 6.3%, p=0.001) and adults (33.3% versus 12.5%, p=5.10(-4)). In children, ASCA IgG were negative in group II and positive in 20% of group I (p=0.01). In adults, the frequency of ASCA IgG was also significantly lower in group II than in group I (9.5% versus 34%, p=0.03). CONCLUSIONS: A high frequency of ASCA has been found in coeliac patients. The frequency of ASCA was not statistically different between patients with successful adherence to GFD and healthy controls.     

Effects of disease activity on anti-Saccharomyces cerevisiae antibodies: implications for diagnosis and follow-up of children with Crohn's disease

BACKGROUND: To determine diagnostic accuracy of anti-Saccharomyces cerevisiae antibodies (ASCA) in identifying children with inflammatory bowel disease (IBD) and to differentiate Crohn's disease (CD) from other IBD forms; and to determine the effect of medical or surgical treatment and of disease location and activity on ASCA titers. METHODS: Serum samples were obtained from 196 IBD children and 142 controls. ASCA IgA and IgG titers were measured by ELISA. Measurements were repeated during the follow up of CD children. RESULTS: ASCA titers were significantly higher in CD than in other IBD and in control patients. Combination of IgA and IgG ASCA positivity was highly specific for CD. Medical treatment and disease location did not influence assay results. Significantly lower ASCA titers were obtained in CD children with intestinal resection compared to CD-affected children who did not undergo surgical resection. ASCA titers correlated significantly with disease activity, and children with severe active disease showed higher ASCA values compared to those in remission. A significant reduction of ASCA was observed during the follow-up of CD children when clinical remission was achieved. CONCLUSIONS: The diagnostic accuracy of ASCA is influenced by disease activity and this suggests an additional use for the follow-up of CD children of this assay.