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.     

Use of biological molecules in the treatment of inflammatory bowel disease

The introduction of biological agents (i.e. antitumour necrosis factor-α and anti-integrin treatments) for the treatment of inflammatory bowel disease (IBD) [i.e. Crohn's disease (CD) and ulcerative colitis] has led to a substantial change in the treatment algorithms and guidelines, especially in CD. However, many questions still remain about the true efficacy and the best treatment regimens. Thus, a need for further treatment options still exists as up to 40% of IBD patients treated with the presently available biologicals do not have positive clinical responses. Better patient selection might maximize the clinical benefit for those in most need of an effective therapy to avoid disabling disease whilst also minimizing the complications associated with therapy. Further, the 'trough-level strategy' may help clinicians to optimize therapy and to avoid loss of response and/or immunogenicity. The idea behind this dosage regimen is that correct dosing must ensure that the patient's lowest level of drug concentration (i.e. the trough level) occurring just before the next drug administration is high enough for the full effect to be seen. Controversy continues regarding the appropriate use of biologicals; therefore, in this review, we focus on considerations that might lead to a more rational strategy for antitumour necrosis factor-α agents in IBD, emphasizing the situations in which the risks may outweigh the benefits. Finally, the need for an appropriate strategy for stopping biological treatment is discussed.     

Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease

BACKGROUND: Activated T cells are more susceptible to apoptosis than resting T cells. As intestinal T cells normally exhibit a higher state of activation, increased apoptosis may be necessary to maintain immune homeostasis in the specialised microenvironment of the mucosa. On the other hand, in Crohn's disease (CD) mucosal T cells are resistant to apoptosis, suggesting abnormal regulation of cell death mechanisms. AIMS: To investigate differences in expression of anti- and proapoptotic Bcl-2 family proteins, key regulators of apoptosis, between circulating and mucosal T cells, and possible alterations in CD. PATIENTS AND METHODS: Lamina propria T cells (LPT) were isolated from 10 control, seven CD, and eight ulcerative colitis (UC) patients, and peripheral blood T cells (PBT) from healthy volunteers. Purified T cells were stained intracellularly for Bcl-2, Bcl-x(L), and Bax, and mean fluorescence intensity measured by flow cytometry. RESULTS: Compared with PBT, the expression level of Bcl-2 and Bax, but not Bcl-x(L), was significantly greater in LPT, resulting in lower Bcl-x(L)/Bax ratios. In PBT, Bax expression was highly and significantly correlated with both Bcl-2 and Bcl-x(L), but correlation with Bcl-2 was absent in LPT. Bax expression in CD, but not UC, LPT was significantly lower than in control LPT, resulting in a significantly higher Bcl-x(L)/Bax ratio. The significant correlation of Bcl-x(L) to Bax was preserved in CD, but not UC, LPT. CONCLUSIONS: Regulation of Bcl-2 family protein expression differs between circulating and mucosal T cells, probably underlying diverse survival potentials. In CD LPT, a low Bax expression and a high Bcl-x(L)/Bax ratio favour resistance to apoptosis and may contribute to the chronicity of inflammation.     

Racial differences in the prevalence of ulcerative colitis and Crohn's disease in Singapore

BACKGROUND: The aim of this study was to determine the prevalence rates of inflammatory bowel disease in the different races in Singapore. METHODS: The patients studied consisted of 58 people with an established diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) as determined by a combination of clinical, radiological, endoscopic and histological criteria. The patients were residents of a well-defined geographical area in the northern part of Singapore and had been referred to the single regional hospital. Epidemiological data including sex, age, ethnicity, family history and disease type and extent were collected from case records and patient interviews. RESULTS:There were 37 UC and 21 CD patients. Of the patients with UC, 67.5% were Chinese, 13.5% were Malay and 19% were Indian. The CD group consisted of 81% Chinese, 9.5% Malay and 9.5% Indian patients. The study population from which the patients were drawn was approximately 0.5 million in size. CONCLUSIONS: The overall prevalence of UC was 6 per 100,000 and of CD was 3.6 per 100,000 in Singapore. There were disproportionately more Indians suffering from UC, with a prevalence of 16.2 per 100,000 in comparison with six per 100,000 for Chinese and seven per 100 000 for Malays. The relative risk of UC in Indians is 2.9-fold greater than for the Chinese (CI= 1.25-6.7) which was statistically significant. This trend was not seen for CD.     

Clinical features and pattern of indeterminate colitis: Crohn's disease with ulcerative colitis-like clinical presentation

Background.Although an accurate diagnosis of inflammatory bowel disease (IBD) and differentiation between ulcerative colitis (UC) and Crohn's disease (CD) can be made in most patients, it is sometimes impossible to distinguish UC from CD even after thorough pathological study. Recently, clinicians have used the term indeterminate colitis (IC) for patients with features of both diseases that overlap temporarily or persistently. The frequency, reasons, and outcome of patients with a clinical diagnosis of IC based on radiological, endoscopic, and histopathological findings were investigated retrospectively. Methods. Based on records of 735 patients with IBD, IC was defined as having features of both UC and CD, with differentiation from each other impossible at least once during the observation period (average 6.8 years) based on diagnostic criteria using endoscopic, radiological, and histological findings. Results. Twenty-three patients were identified as having IC. They were classified into three patterns according to the clinical cource and the final diagnosis: (1) UC changing to CD (n = 8); (2) CD changing to UC (n = 5); and (3) UC or CD (n = 10). The frequency of IC was 24.5%–43.4% of colitis-type CD (n = 53), 2.3%–6.5% of all CD (n = 352), and 3.1% of IBD (n = 735). The reasons for the indetermination were temporary (56.5%) or persistent (43.5%) overlapping of UC-like and CD-like presentations. Treatment of IC was inappropriate in only two patients, and the prognoses of all patients except one were fairly good. Conclusions. Overlapping of UC-like presentations (persistent bloody stool and diffuse colitis) was frequently observed with Crohn's colitis but less so in CD patients during their clinical course. The basis of differentiation and treatment of IC needs more attention.     

Decreased Gelatin-Binding Fibronectin in Patients with Chronic Inflammatory Bowel Diseases

The plasma fibronectin concentration (PF) was measured in 48 patients with chronic inflammatory bowel disease (CIBD) and in 48 age- and sex-matched healthy controls, using electroimmunoassay and a functional (gelatin-binding) assay. Whereas no difference in immunochemically measured PF was found between the two groups, patients with CIBD had significantly lower gelatin-binding PF than healthy controls (p < 0.001). Immunochemically measured PF increased, whereas functionally measured PF tended to decrease with increasing disease activity.     

PMN-elastase in assessment of patients with inflammatory bowel disease

PMN-elastase is a proteinase released by activated neutrophils. PMN-elastase was determined in two independent populations with inflammatory bowel disease. In an unselected population of 70 consecutive patients with Crohn's disease and 24 patients with ulcerative colitis with different degrees of disease activity plasma PMN-elastase levels were statistically significantly higher in patients with active than in patients with inactive disease [Crohn's disease: 80.5±33.2 ng/ml vs 60.1±24.6 ng/ml (means±sd),P=0.0017; ulcerative colitis: 98.2±54.9 ng/ml vs 59.2±16.8 ng/ml,P=0.026]. PMN-elastase levels in feces were also higher in patients with active Crohn's disease (23.6±15.3 ng/g vs 13.6±12.5 ng/g,P=0.0021) and active ulcerative colitis (46.5±60.5 ng/g vs 20.2±25.0 ng/g,P=0.46), but the difference reached significance only in Crohn's disease. Correlation of disease activity and PMN-elastase in individual patients showed a statistically significant correlation between plasma and fecal elastase concentrations and disease activity in ulcerative colitis (plasma:r=0.72,P<0.001; feces:r=0.423,P<0.001) but not fecal elastase concentrations (r=0.0083,P=0.485) correlated significantly with disease activity. Plasma PMN-elastase correlated weakly with fecal PMN-elastase levels in Crohn's disease (r=0.431,P<0.01) and in ulcerative colitis (r=0.515,P=0.05). In 28 patients with highly active Crohn's disease [median severity activity index (SAI) 203] and 11 patients with highly active ulcerative colitis [median Rachmilewitz index (RI) 14] studied before and four weeks after steroid therapy, treatment lowered the median SAI to 140 and the median RI to 4.5. Mean plasma elastase concentrations decreased concomitantly from 83±44.9 ng/ml to 61.8±25.8 (P=0.0035) in patients with Crohn's disease and from 110±49.5 to 71.6±28.8 ng/ml (P=0.0069) in patients with ulcerative colitis. In conclusion, there is a release of PMN-elastase in active IBD, which can be detected in plasma as well as in feces. Plasma elastase levels reflect disease activity in patients with IBD. The variation of the data and the large overlap between different groups, however, strongly reduce the clinical value.This research was supported by the SFB 154 of the Deutsche Forschungsgemeinschaft. V. Gross is supported by a Heisenberg-Stipendium of the Deutsche Forschungsgemeinschaft.     

Understanding the complications of anti‐tumor necrosis factor therapy in East Asian patients with inflammatory bowel disease

Remarkable advances have been made in the treatment of inflammatory bowel disease since the introduction of anti‐tumor necrosis factor‐α agents, especially for patients who are refractory to or cannot tolerate conventional therapies. Currently, infliximab, adalimumab, and golimumab are available in the East Asian medical market, and these agents have been shown to be effective for inducing and maintaining long‐term remission of inflammatory bowel disease. Despite their clinical benefits, anti‐tumor necrosis factor therapy can also lead to increased vulnerability to infections, development of autoimmune diseases and malignancy, and decreased immunogenicity of vaccinations. Because infectious diseases, such as tuberculosis, hepatitis, and influenza, remain major health problems in East Asia, more cautious use of biologics is needed. To further improve treatment efficacy and safety, close monitoring of inflammation, regular surveillance for malignancy, and regularly scheduled vaccinations are needed. Treatment strategies for biologics should be customized to meet the needs of different patients.     

Monozygotic twins with Crohn's disease and ulcerative colitis: a unique case report

Background—A large number of monozygotic anddizygotic twin pairs with inflammatory bowel disease have beenreported. To date no twin pair has developed phenotypically discordantinflammatory bowel disease. This case report is the first documentedoccurrence of discordant inflammatory bowel disease occurring inmonozygotic twins.
Case report—Twenty two year old identical maletwins presented within three months of each other with inflammatorybowel disease that proved to be discordant in overall disease type,disease distribution, clinical course, and histopathological findings. Twin 1 developed a severe pancolitis necessitating total colectomy while twin 2 developed a predominantly distal patchy colitis with frequent granulomas, controlled by aminosalicylates. Twin 1 was antineutrophil cytoplasmic antibody (ANCA) negative at the time oftesting while twin 2 (Crohn's disease) was ANCA positive.Significantly, the twins possessed the HLA type DR3-DR52-DQ2 previouslyassociated with extensive colitis.
Conclusion—This case report confirms the importantrole played by genetic factors in the development of inflammatory bowel disease. It also highlights the crucial role of undeterminedenvironmental agents in dictating disease expression and phenotype.

Keywords:monozygotic twins; ulcerative colitis; Crohn'sdisease; inflammatory bowel disease

     

Fatigue in a population-based cohort of patients with inflammatory bowel disease 20 years after diagnosis: The IBSEN study

Objective: Fatigue is a major concern for patients with ulcerative colitis (UC) and Crohn’s disease (CD), but evidence from population-based studies regarding fatigue in long-standing inflammatory bowel disease (IBD) patients is scarce. Our aims were to assess fatigue scores and the prevalence of chronic fatigue in IBD patients 20 years after diagnosis and to identify variables associated with fatigue in this cohort.

Methods: Twenty years after diagnosis, patients from a cohort with incident IBD were invited to a follow-up visit that included a structured interview, a clinical examination, laboratory tests and the Fatigue Questionnaire (FQ). Fatigue scores were obtained, and factors associated with fatigue were assessed via linear and logistic regression analyses.

Results: Of the 599 invited patients, 440 (73.5%) completed the FQ. Among those with active disease, we found significantly higher fatigue scores than among those with quiescent disease (fatigue scores: UC 17.1 versus 12.4, p?<?.001, and CD 17.5 versus 13.3, p?<?.001). The fatigue scores of those with quiescent disease were comparable with those of the reference population. Chronic fatigue was more frequent among IBD patients than in the reference population. Factors associated with fatigue included self-perceived disease activity, poor sleep quality, anxiety and depression.

Conclusion: At 20 years after IBD diagnosis, fatigue scores were higher and chronic fatigue was more frequent among IBD patients with active disease than in the reference population and among those with quiescent IBD. Subjectively perceived disease activity, sleep quality, anxiety and depression were associated with fatigue in IBD patients.     

Serious infections in patients with inflammatory bowel disease receiving anti-tumor-necrosis-factor-alpha therapy: an Australian and New Zealand experience

Background and Aim: Anti‐tumor‐necrosis‐factor‐alpha (anti‐TNF‐α) medications are effective in inflammatory bowel disease (IBD), but have an increased risk of tuberculosis (TB) and serious infections. The aim of this study was to examine the Australian/New Zealand experience of serious infections and TB in IBD patients receiving anti‐TNF‐α therapy from 1999–2009. Methods: Serious infections, defined as ‘requiring hospital admission’ and TB cases in patients receiving, or within 3 months following, anti‐TNF‐α therapy were analyzed across Australia and New Zealand. Patient demographics, IBD medications, duration of anti‐TNF‐α therapy, and infection details were collected. Results: A total of 5562 IBD patients were managed across the centers. Of these, 489 (16.8%) Crohn's disease and 137 (5.2%) ulcerative colitis patients received anti‐TNF‐α therapy. There were three cases of latent TB that received prophylaxis prior to anti‐TNF‐α therapy. No cases of active TB were reported. Fourteen (2.2%) serious infections occurred. Seven occurred in patients receiving anti‐TNF‐α therapy for less than 6 months, including two cases of primary Varicella zoster (VZV), two cases of Pneumocystis jiroveci pneumonia, two cases of Staphylococcus aureus bacteremia, and one severe flu‐like illness. Six patients were taking additional immunosuppressive medications. The other seven infections occurred after 6 months (mean 32.6 ± 24.3 months) and included one case of primary VZV, one flu‐like illness, and five bacterial infections. All infections resolved with treatment. Conclusion: TB is a very rare complication of anti‐TNF‐α therapy in Australia and New Zealand. Serious infections are uncommon but early opportunistic infections with Pneumocystis jiroveci pneumonia suggest a need for vigilance in patients on multiple immunosuppressive medications. VZV vaccination prior to immunosuppressive therapy should be considered in VZV‐naïve patients.     

Decreased trabecular bone mineral density in newly diagnosed inflammatory bowel disease patients in Korea

BACKGROUND: Decreased bone mineral density (BMD) is common in Western patients with inflammatory bowel disease (IBD). However, BMD has never been studied in Asia where the demographic and socio-economic status are different from the West. The aim of this study was to investigate the prevalence and mechanisms of osteopenia in newly diagnosed Korean patients with IBD. METHODS: We studied 14 patients with Crohn's disease (CD) and 25 patients with ulcerative colitis (UC), all of whom had never been treated with corticosteroids. Bone mineral density was measured in the lumbar spine and the femoral neck by dual energy X-ray absorptiometry. Biochemical parameters including serum osteocalcin, parathyroid hormone, plasma inactive and active vitamin D, and urinary deoxypyridinoline were measured. RESULTS: The BMD Z score at the lumbar spine was lower both in CD and in UC patients, but there was no significant difference between the two groups. There was no significant difference in nutritional status or biochemical parameters of bone metabolism between patients with a normal BMD and those with a decreased BMD. CONCLUSIONS: Low BMD at the lumbar spine is common in newly diagnosed Korean patients with IBD, a result which is similar to Western studies. The mechanism for low bone mass remains undetermined; however, nutritional status and hormonal parameters of bone metabolism, and ethnic differences are not likely to be an important factor in the pathogenesis of this bone loss.     

Cyclosporin Pharmacokinetics after Intravenous and Oral Administration in Patients with Crohn's Disease

Cyclosporin kinetics were estimated after single-dose intravenous and oral administration in 12 patients with Crohn's disease in accordance with a three-compartment model with zero-order inputs. Cyclosporin was measured in whole blood with a specific monoclonal radioimmunoassay. The median bioavailability (f) was 23.7% (range, 0–49.1%); the distribution volume at steady state, 2.31/kg (range, 1.0–3.5 1/kg); clearance (CL), 7.6ml/min/kg (range, 4.8–10.8 ml/min/kg); and t_1/2(z) 7.9 h (range, 3.2–13.9 h). Both the extent and rate of bioavailability were significantly lower in six of the patients, who had low or undetectable cyclosporin levels during a preceding therapeutic trial. After repeated oral administration significant correlations were found between the single-dose f/CL ratios and the steady-state blood concentrations, indicating that the kinetics did not change markedly with time. We conclude that the disposition kinetics of cyclosporin in patients with Crohn's disease are comparable to those of other groups. whereas the bioavailability may be decreased. It is suggested that cyclosporin levels should be monitored closely, and intravenous treatment should be considered in patients with a rapid gut transit time. because cyclosporin absorption seems to follow zero-order kinetics.     

Fracture risk is increased in Crohn's disease, but not in ulcerative colitis

AIMS: To study fracture rates and risk factors for fractures in patients with Crohn's disease and ulcerative colitis. METHODS: 998 self administered questionnaires were issued to members of the Danish Colitis/Crohn Association, and 1000 questionnaires were issued to randomly selected control subjects. 845 patients (84.5%) and 645 controls (65.4%) returned the questionnaire (p<0.01). 817 patients and 635 controls could be analysed. RESULTS: Analysis was performed on 383 patients with Crohn's disease (median age 39, range 8-82 years; median age at diagnosis 26, range 1-75 years), 434 patients with ulcerative colitis (median age 39, range 11-86 years; median age at diagnosis 29, range 10-78 years), and 635 controls (median age 43, range 19-93 years, p<0.01). The fracture risk was increased in female patients with Crohn's disease (relative risk (RR) = 2.5, 95% confidence interval (CI) 1.7-3.6), but not in male patients with Crohn's disease (RR = 0.6, 95% CI 0.3-1.3) or in patients with ulcerative colitis (RR = 1.1, 95% CI 0.8-1.6). An increased proportion of low energy fractures was observed in patients with Crohn's disease (15.7% versus 1.4 % in controls, 2p<0. 01), but not in patients with ulcerative colitis (5.4%, 2p=0.30). The increased fracture frequency in Crohn's disease was present for fractures of the spine, feet, and toes and fractures of the ribs and pelvis. Fracture risk increased with increasing duration of systemic corticosteroid use in Crohn's disease (2p=0.028), but not in ulcerative colitis (2p=0.50). CONCLUSIONS: An increased risk of low energy fractures was observed in female patients with Crohn's disease, but not in male patients with Crohn's disease or in patients with ulcerative colitis.     

Diagnostic role of anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic antibodies in patients with inflammatory bowel disease

PURPOSE: Perinuclear antineutrophil cytoplasmic autoantibody is known to be a marker for ulcerative colitis, and anti-Saccharomyces cerevisiae Mannan antibody is a serologic marker associated with Crohns disease. The aim of this study was to assess the value of detecting perinuclear antineutrophil cytoplasmic autoantibody and/or anti-Saccharomyces cerevisiae Mannan antibody for the diagnosis of ulcerative colitis, Crohns disease, Behçets colitis, and tuberculous colitis. METHODS: Serum samples were obtained from 85 patients with Crohns disease, 77 with ulcerative colitis, 36 with Behçets colitis, 14 with tuberculous colitis, 20 healthy controls, and 21 first-degree relatives of patients with Crohns disease. Determination of perinuclear antineutrophil cytoplasmic autoantibody and anti-Saccharomyces cerevisiae Mannan antibody was performed with the standardized indirect immunofluorescence technique and an enzyme-linked immunosorbent assay, respectively. RESULTS: A relatively high percentage of patients with Crohns disease (49.4 percent), relatives of Crohns disease patients (61.9 percent), and patients with Behçets disease (41.7 percent) tested seropositive for anti-Saccharomyces cerevisiae Mannan antibody compared with normal controls (10 percent). In cases of ulcerative colitis, 44.2 percent tested seropositive for perinuclear antineutrophil cytoplasmic autoantibody, whereas the controls showed 0 percent positivity. The combination of a positive anti-Saccharomyces cerevisiae Mannan antibody test and a negative perinuclear antineutrophil cytoplasmic autoantibody yielded a sensitivity and specificity of 48.2 and 87 percent, respectively, for Crohns disease. The combination of a positive perinuclear antineutrophil cytoplasmic autoantibody test and a negative anti-Saccharomyces cerevisiae Mannan antibody test yielded a sensitivity and specificity of 36.4 and 97.6 percent, respectively, for ulcerative colitis. CONCLUSION: Anti-Saccharomyces cerevisiae Mannan antibody may be associated with Crohns disease and Behçets disease and perinuclear antineutrophil cytoplasmic autoantibody with ulcerative colitis. A combination of both tests may aid the differential diagnosis of inflammatory bowel disease.     

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

The Asia–Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia–Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all‐encompassing, and future revisions are likely as new data continue to emerge.     

Anti-pancreatic antibody in Turkish patients with inflammatory bowel disease and first-degree relatives

AIM: To identify the role of anti-pancreatic antibody (PAB) in the diagnosis of inflammatory bowel diseases (IBD) among Turkish patients, and its frequency in firstdegree relatives.METHODS: PAB and anti-Saccharomyces cerevisiae (ASCA) were examined in serum samples of 214 subjects including patients with Crohn’s disease (CD, n = 64), ulcerative colitis (UC, n = 63), first-degree relatives of patients with CD (n = 25), first-degree relatives of patients with UC (n = 28),and a control group with gastrointestinal symptoms other than (IBD) (n = 34) by indirect immunofluorescence Positivity of PAB and ASCA was compared in terms of Vienna classification, disease activity and medications used.RESULTS: In terms of PAB positivity, no difference was found between patients with CD (14.1%) and UC (7.9%) however, significant difference was observed between patients with CD and subjects in the control group (P < 0.05). No difference was found between patients with CD and their relatives in terms of ASCA positivity, whereas a significant difference was found between other groups (P < 0.001). Compared to ASCA, the sensitivity of the PAB was 19% (7/37), its specificity was 93% (25/27), positive predictive value was 77% (7/9) and negative predictive value was 45% (25/55). ASCA was found with significantly higher prevalence in patients with CD activity index > 150 (P < 0.05).CONCLUSION: PAB is valuable in the diagnosis of IBD rather than CD, but cannot be used alone for diagnostic purposes. PAB is not superior to ASCA in CD diagnosis and in detecting CD among relatives of patients with CD.     

Detection of Listeria monocytogenes by polymerase chain reaction in intestinal mucosal biopsies from patients with inflammatory bowel disease and controls

BACKGROUND AND AIMS: Components of the intestinal microflora are believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD) in genetically susceptible hosts acting either as a non-specific antigenic stimulus or as a specific pathogen. Listeria monocytogenes has been suggested as an organism with the potential to cause IBD. The objective of the present study was to investigate the prevalence of L. monocytogenes DNA in intestinal biopsies from patients with IBD and from non-IBD controls by using nested polymerase chain reaction (PCR). METHODS: The DNA was extracted from 274 colonoscopic biopsies, which were obtained from 23 patients with Crohn's disease (CD), 28 with ulcerative colitis (UC) and 39 non-IBD control patients. Nested PCR amplification was used to detect the presence of the L. monocytogenes listeriolysin O (hly) gene. The sequences of positive PCR products were determined and compared with databases. RESULTS: The sensitivity of our nested PCR was 10 fg L. monocytogenes DNA. Overall, L. monocytogenes DNA was detected in 13.0% patients with CD, 17.9% patients with UC and 25.6% non-IBD control patients or in 29 of 274 (10.6%) endoscopic biopsies. Among them, L. monocytogenes DNA was detected in four of 67 (6%) biopsies from patients with CD, five of 94 (5.3%) biopsies from patients with UC and 20 of 113 biopsies (17.7%) from non-IBD control patients. Sequence analysis of positive PCR products demonstrated more than 95% similarity to the hly gene sequence of L. monocytogenes, confirming the authenticity of our PCR products. CONCLUSION: Listeria monocytogenes DNA was detected in the intestine of both patients with IBD and in non-IBD control patients, probably reflecting the widespread presence of this organism in the environment. The low yield of positive biopsies in our IBD patients (5-6%) and the fact that the detection rate of L. monocytogenes DNA was similar in endoscopic biopsies from IBD patients and non-IBD controls does not support a direct role for L. monocytogenes in the pathogenesis of IBD, at least in New Zealand patients.