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.     

Plasma leptin and ghrelin concentrations in patients with Crohn＇s disease

AIM: To determine the concentrations of leptin and ghrelin, which have opposite effects on appetite, energy expenditure, and weight control, in the plasma of patients with Crohn's disease (CD), which is often associated with weight loss and malnutrition. METHODS: Plasma leptin and ghrelin concentrations were determined in 28 outpatients with CD by radioimmunoassay. Age- and sex-matched controls with and without Helicobacter pylori (H pylori) infection (28 for each) were enrolled in the study. Circulating levels of these hormones were assessed with respect to CD activity, disease localization and medical treatment. RESULTS: There were no significant differences in ghrelin levels between CD patients and H pylori -negative controls. However, circulating ghrelin levels were significantly lower in H pylori-infected subjects than in CD patients and uninfected controls. Plasma leptin levels were comparable among the groups. Localization and medication profile had no significant impact on circulating ghrelin and leptin levels. CONCLUSION: Apart from H pylori infection, CD itself has no significant influence on circulating ghrelin and leptin levels in the outpatients who were mostly in inactive state.     

Gallbladder bile composition in patients with Crohn＇s disease

AIM:To further elucidate the pathogenesis andmechanisms of the high risk of gallstone formation inCrohn's disease.METHODS:Gallbladder bile was obtained from patientswith Crohn's disease who were admitted for electivesurgery (17 with ileal/ileocolonic disease and 7 withCrohn's colitis).Fourteen gallstone patients servedas controls.Duodenal bile was obtained from tenhealthy subjects before and after the treatment withursodeoxycholic acid.Bile was analyzed for biliary lipids,bile acids,bilirubin,crystals,and crystal detection time(CDT).Cholesterol saturation index was calculated.RESULTS:The biliary concentration of bilirubin wasabout 50% higher in patients with Crohn's disease thanin patients with cholesterol gallstones.Ten of the patientswith Crohn's disease involving ileum and three of thosewith Crohn's colitis had cholesterol saturated bile.Fourpatients with ileal disease and one of those with colonicdisease displayed cholesterol crystals in their bile.About1/3 of the patients with Crohn's disease had a shortCDT.Treatment of healthy subjects with ursodeoxycholicacid did not increase the concentration of bilirubin induodenal bile.Several patients with Crohn's disease,with or without ileal resection/disease had gallbladderbile supersaturated with cholesterol and short CDT andcontained cholesterol crystals.The biliary concentrationof bilirubin was also increased in patients with Crohn'scolitis probably not due to bile acid malabsorption.CONCLUSION:Several factors may be of importance forthe high risk of developing gallstones of both cholesteroland pigment types in patients with Crohn's disease.     

Crohn＇s disease and risk of fracture： does thyroid disease play a role？

AIM: To assess the role of thyroid disease as a risk for fractures in Crohn‘s patients.METHODS: A cross-sectional study was conducted from 1998 to 2000. The study group consisted of 210 patients with Crohn‘s disease. A group of 206 patients without inflammatory bowel disease served as controls. Primary outcome was thyroid disorder. Secondary outcomes included use of steroids, immunosuppressive medications, surgery and incidence of fracture.RESULTS: The prevalence of hyperthyroidism was similar in both groups. However, the prevalence of hypothyroidism was lower in Crohn‘s patients (3.8 % vs 8.2 %, P=0.05).Within the Crohn‘s group, the use of immunosuppressive agents (0 % vs11%), steroid usage (12.5 % vs37 %), small bowel surgery (12.5 % vs 28 %) and large bowel surgery(12.5 % vs 27 %) were lower in the hypothyroid subset as compared to the euthyroid subset. Seven (3.4 %) Crohn‘s patients suffered fracture, all of whom were euthyroid.CONCLUSION: Thyroid disorder was not found to be associated with Crohn‘s disease and was not found to increase the risk for fractures. Therefore, screening for thyroid disease is not a necessary component in the management of Crohn‘s disease.     

Epidemiology and outcome of Crohn＇s disease in a teaching hospital in Riyadh

AIM: To know the epidemiology and outcome of Crohn‘s disease at King Khalid University Hospital, Riyadh, Saudi Arabia and to compare the results from other world institutions.METHODS: A retrospective analysis of patients seen for 20 years (between 1983 and 2002). Individual case records were reviewed with regard to history, clinical, findings from colonoscopy, biopsies, small bowel enema, computerized tomography scan, treatment and outcome.RESULTS: Seventy-seven patients with Crohn‘s disease were revisited, 13% presented the disease in the first 10 years and 87% over the last 10 years. Thirty-three patients (42.9%) were males and 44 (57.1%) were females. Age ranged from 11-70 years (mean of 25.3+11.3 years). Ninety-two (92%) were Saudi. The mean duration of symptoms was 26+34.7 mo. The mean annual incidence of the disease over the first 10 years was 0.32:100 000 and 1.66:100 000 over the last 10 years with a total mean annual incidence of 0.94:100 000 over the last 20 years. The chief clinical features included abdominal pain, diarrhea, weight loss,anorexia, rectal bleeding and palpable mass. Colonoscopic findings were abnormal in 58 patients (76%) showing mostly ulcerations and inflammation of the colon. Eighty nine percent of patients showed nonspecific inflammation with chronic inflammatory cells and half of these patients revealed the presence of granulomas and granulations on bowel biopsies. Similarly, 69 (89%) of small bowel enema results revealed ulcerations (49%), narrowing of the bowel lumen (42%), mucosal thickening (35%) and cobblestone appearance (35%). CT scan showed abnormality in 68 (88%) of patients with features of thickened loops (66%) and lymphadenopathy (37%). Seventy-eight percent of patients had small and large bowel disease, 16% had small bowel involvement and only 6% had colitis alone. Of the total 55 (71%) patients treated with steroids at some point in their disease history, a satisfactory response to therapy was seen in 28 patients (51%) while 27 (49%) showed recurrences of the condition with mild to moderate symptoms of abdominal pain and diarrhea most of which were due to poor compliance to medication. Seven patients (33%) remained with active Crohn‘s disease. Nine (12%) patients underwent surgery with resections of some parts of bowel, 2 (2.5%) had steroid side effects, 6 (8%) with perianal Crohn‘s disease and five (6.5%) with fistulae.CONCLUSION: The epidemiological characteristics of Crohn‘s disease among Saudi patients are comparable to those reported from other parts of the world. However the incidence of Crohn‘s disease in our hospital increased over the last 10 years. The anatomic distribution of the disease is different from other world institutions with less isolated colonic affection.     

Intestinal permeability and its association with the patient and disease characteristics in Crohn＇s disease

AIM：To assess the intestinal permeability （IP） in patients with Crohn＇s disease （CD） and study the association of IP with the patient and disease characteristics.
METHODS： One hundred and twenty five consecutive patients of CD （Males： 66） were diagnosed on the basis of a combination of standard clinical, endoscopic, imaging and histological features. CD activity index （CDAI） was used to calculate the activity of the disease while the behavior of the disease was assessed by the modified Montreal classification. IP was measured by the ratio of the percentage excretion of ingested doses of lactulose and mannitol in urine （LMR）. The upper limit of normality of LMR （0.037） was derived from 22 healthy controls.
RESULTS： Thirty six percent of patients with CD had increased IP. There was no significant difference in mannitol excretion （patients vs controls = 12.5% vs 14.2%, P = 0.4652）, but lactulose excretion was significantly higher in patients compared to healthy controls （patients vs controls = 0.326% vs 0.293%, P = 0.0391）. The mean LMR was also significantly higher in the patients as compared to healthy controls [0.027 （0.0029-0.278） vs 0.0164 （0.0018-0.0548）, P = 0.0044]. Male patients had a higher LMR compared to females [0.036 （95% CI 0.029, 0.046） vs 0.022 （95% CI 0.0178, 0.028） （P = 0.0024）, though there was no difference in the number of patients with abnormal IP in boththe sexes. Patients with an ileo-colonic disease had a higher LMR than those with only colonic disease [0.045 （95% CI 0.033, 0.06） vs 0.021 （95% CI 0.017, 0.025） （P 〈 0.001）]. Of patients with ileo-colonic disease, 57.8% had an abnormal IP, compared to 26.7% with colonic and 15.6% with small intestinal disease. Patients with a stricturing disease had significantly higher LMR compared to non-fistulising non-stricturing disease [0.043 （95% CI 0.032, 0.058） vs 0.024 （95% CI 0.019, 0.029） （P = 0.0062）]. There was no correlation of IP with age, disease activ     

Screening for celiac disease in Down＇s syndrome patients revealed cases of subtotal villous atrophy without typical for celiac disease HLA-DQ and tissue transglutaminase antibodies

AIM: To investigate the prevalence of celiac disease (CD) as well as CD marker antibodies and susceptibility HLA-DQ haplotypes in 134 karyotyped Down's syndrome (DS) patients. METHODS: Immunoglobulin A (IgA) and G (IgG) type anti-gliadin antibodies (AGA), IgA type anti-tissue transglutaminase (tTG) antibodies (anti-tTG) with antigen of guinea pig and human source were determined by enzyme-linked immunosorbent assay and endomysium antibodies (EMA) by indirect immunofluoresence test. HLA-DQA1*0501/DQB1*0201 (DQ2) was revealed by polymerase chain reaction. Celiac disease was diagnosed by revised ESPGHAN criteria. RESULTS: 41% of DS patients had AGA, 6.0% IgA anti-tTG with guinea pig antigen, and 3.0 % IgA EMA (all positive for anti-tTG with human tTG). Subtotal villous atrophy was found in 5 out of 9 DS patients who had agreed to small bowel biopsy. One of them had DQA1*0501/DQB1*0201 and anti-tTG and EMA i.e. typical for CD markers (this case also fulfilled the ESPGHAN diagnostic criteria), but other four lacked these markers. Three non-biopsied DS patients had also most probably CD because DQA1*0501/DQB1*0201 and IgA anti-tTG (EMA) were detected. Thus, the prevalence of CD among our DS patients population is 3.0 % (95 % of confidence interval [CI]: 0.1-5.9 %). CONCLUSION: We confirm the increased frequency of CD among DS patients. In addition, we have revealed a subgroup of patients with subtotal villous atrophy but without characteristic for CD immunological and genetic markers. Whether these cases represent CD (with atypical immunopathogenesis) or some other immune enteropathy, requires further investigations.     

Transplantation of an eight-organ multivisceral graft in a patient with frozen abdomen after complicated Crohn＇s disease

To report an extended multivisceral transplantation (MVTx) including right kidney and ascending colon in a patient with complicated Crohn's disease (CD). A 36-year old female suffering from short bowel syndrome and frozen abdomen due to fistulizing CD after multiple abdominal operations underwent MVTx of eight organs including stomach, pancreatoduodenal complex, liver, intestine, ascending colon, right kidney, right adrenal gland, and greater omentum in November 2003. Immunosuppression consisted of alemtuzumab, tacrolimus and steroids. The patient was off parenteral nutrition by postoperative wk 3. She experienced one episode of pneumonia. The patient recovered completely and discharged 2.5 mo and was doing well 30 mo after MVTx. This is one of the very rare cases in which a complete mulitivisceral graft of eight abdominal organs was transplanted orthotopically.     

Effect of infliximab on small bowel stenoses in patients with Crohn＇s disease

AIM： To assess prospectively small bowel stenoses in Crohn＇s disease （CD） patients treated with infliximab using Small Intestine Contrast Ultrasonography （SICUS）. METHODS： Twenty patients （M 12, age, 42.7 ± 11.8 years）, 15 of whom showed obstructive symptoms indicating the presence of small bowel stenosis, and 5 without stenosis, were treated with infliximab （5 mg/kg at wk 0, 2, 6 and 5 mg/kg every 8 wk thereafter） for steroid refractoriness, fistulizing disease, or to avoid high-risk surgery. SICUS was performed at the induction phase and at regular time intervals during the followup period of 34.7 ± 16.1 mo （range 7-58）. Small bowel stenoses were detected by SICUS, endoscopy and MRI. RESULTS： In no case was progression of stenoses or the appearance of new ones seen. Of the 15 patients with stenosis, 5 stopped treatment after the induction phase （2 for no response, 3 for drug intolerance, one of whom showed complete regression of one stenosis）. Among the remaining 10 patients, a complete regression of 8 stenoses （1 stenosis in 5 patients and 3 stenoses in one patient） was observed after 6-22 infliximab infusions. CONCLUSION： In patients with CD treated with infliximab we observed： （a） No progression of small bowel stenosis and no appearance of new ones, （b） Complete regression of 1/22 stenosis after the induction phase and of 8/15 （53.3%） stenosis after 6-22 infusions during maintenance therapy.     

Role of perioperative parenteral nutrition in severely malnourished patients with Crohn＇s disease

AIM: To evaluate the effect of perioperative parenteral nutrition on serum immunoglobulin, weight change, and post-operative outcome in severely malnourished patients with Crohn's disease. METHODS: Thirty-two severely malnourished patients with Crohn's disease who had undergone surgery in our hospital were reviewed. Sixteen patients who received perioperative parenteral nutrition were enrolled in the study group, and the other 16 patients who did not receive parenteral nutrition were enrolled in the control group. Serum immunoglobulin, body mass index (BMI), liver function, weight change, and postoperative complications were evaluated. RESULTS: Serum IgM levels elevated 1 wk before surgery in both groups, and decreased to normal value (from 139±41 to 105±29 mg/dL, P= 0.04) 4 wk after operation in the study group, while no significant changes was noted in the control group (from 133±16 to 129±13 mg/dL, P=0.34). There were no significant changes in concentrations of IgG and IgA. The BMI of the study group increased from 13.9±0.6 to 15.3±0.7 kg/m~2 (P=0.02) with no significant change in the control group (14.1±0.7 and 14.5±0.5, respectively, P= 0.81). The percentage of resuming work was higher in the study group than in the control group. CONCLUSION: Perioperative parenteral nutrition possibly ameliorates the humoral immunity, reverses malnutrition, and facilitates rehabilitation.     

Seroreactivity against Saccharomyces cerevisiae in patients with Crohn′s disease and celiac disease

AIM:To explore whether there was anti-Saccharomyces cerevisiae antibodies (ASCA) positivity in our patients with biopsy-confirmed celiac disease.METHODS: A cohort of patients with inflammatory bowel diseases (42 patients with Crohn's disease and 10 patients with ulcerative colitis) and gluten sensitive enteropathy (16patients) from Debrecen, Hungary were enrolled in the study.The diagnosis was made using the formally accepted criteria.Perinuclear antineutrophil cytoplasmic antibodies (pANCA)and antiS-accharomyces cerevisiae antibodies (ASCA),antiendornysium antibodies (EMA), antigliadin antibodies (AGA) and anti human tissue transglutaminase antibodies (tTGA) were investigated.RESULTS: The results showed that ASCA positivity occurred not only in Crohn's disease but also in Celiac disease and in these cases both the IgG and IgA type antibodies were proved.CONCLUSION: It is conceivable that ASCA positivity correlates with the (auto-) immune inflammation of small intestines and it is a specific marker of Crohn's disease.     

Seroreactivities against Saccharomyces cerevisiae and Mycobacterium avium subsp. paratuberculosis p35 and p36 antigens in Crohn's disease patients

Crohn's disease (CD) is an idiopathic chronic inflammatory bowel disease (IBD). Accurate diagnosis of the disease is of great clinical importance to assess its prognosis and success of therapy. Recent studies have validated and confirmed the potential utility of anti-Saccharomyces cerevisiae (baker's yeast; ASCA) IgG/IgA antibodies and anti-M. avium ss. paratuberculosis p35/p36 antibodies, separately, as serological markers to identify patients with CD. The efficacy of these markers was evaluated in the same patients with Crohn's disease. The anti-ASCA IgA/IgG and the anti-M. avium ss. paratuberculosis p35/p36 antibodies were positive in 60% (36/60) and 86.7% (52/60) of CD patients, respectively. When all the serologic markers were considered, the sensitivity in detecting CD was increased to 95.0% (57/60); 21 of 24 ASCA-negative patients were p35/p36-positive and five of eight of p35/p36-negative patients were ASCA-positive. This investigation further establishes the utility of p35 and p36 recombinant clones for the diagnosis of CD, and reveals the complimentary role of ASCA and p35 and p36 for effective detection of CD. Larger studies are needed to investigate the combined use of these serologic markers for the diagnosis of CD.     

High prevalence of celiac disease among patients affected by Crohn's disease

BACKGROUND: Recent literature has shown a correlation between Crohn's disease (CD) and celiac disease, but a prospective study has not been performed. Our aim was to evaluate the prevalence of celiac disease in a consecutive series of patients affected by CD, in whom the disease was diagnosed for the first time. METHODS: From January to December 2004, we diagnosed 27 patients affected by CD (13 men and 14 women; mean age, 32.3 yrs; range, 16-69 yrs). In all patients, we performed antigliadin, antiendomysium, and antitransglutaminase antibody tests, and the sorbitol H2 breath test evaluation. In case of antibodies and/or sorbitol positivity, esophagogastroduodenoscopy was performed for a small bowel biopsy. RESULTS: Antigliadin, antiendomysium, and antitransglutaminase antibody tests were positive in 8/27 (29.63%), 4/27 (14.81%), and 5/27 (18.52%) patients, respectively, whereas the sorbitol H2 breath test was positive in 11/27 (40.74%) patients: all of them underwent esophagogastroduodenoscopy. Nine of 11 patients showed signs of duodenal endoscopic damage, and 5/9 (55.55%) showed histologic features of celiac disease (18.52% of overall CD population studied): 2 showed Marsh IIIc lesions (1 patient affected by ileal CD and 1 affected by ileo-colonic CD), 2 showed Marsh IIIb lesions (all of them affected by ileo-colonic CD), 1 showed a Marsh IIIa lesion (1 patient affected by colonic CD). CONCLUSIONS: Prevalence of celiac disease seems to be high among patients affected by CD, and this finding should be kept in mind at the time of the first diagnosis of CD; a gluten-free diet should be promptly started.     

Association of asymptomatic celiac disease and Crohn's disease

A 24-year-old woman had Crohn's colitis which had been diagnosed in 1997. The patient was given sulfazalazine and responded well. Antiendomysial and antigliadin antibodies were positive. Diagnosis of celiac disease was confirmed by duodenal biopsy showing villous atrophy and an increased number of lymphocytes infiltrating the epithelium. Few cases associating Crohn's disease and celiac disease have been reported. This case illustrates the complexity of the pathogenic mechanisms in these two disease. Our patient required a gluten-free diet although the celiac disease was asymptomatic, basically to avoid the risk of malignancy associated with celiac disease.     

Decreased anti-Saccharomyces cerevisiae antibody titer by mesalazine in patients with Crohn's disease

BACKGROUND: Saccharomyces cerevisiae may contribute to the pathophysiology of Crohn's disease. We determined serum anti-Saccharomyces cerevisiae antibody (ASCA) levels in patients with inflammatory bowel disease. METHODS AND RESULTS: Immunoglobulin G (IgG) ASCA was measured by using an ELISA in serum samples from 19 patients with ulcerative colitis, 18 patients with Crohn's disease and 7 healthy controls. The ASCA level was significantly higher in patients with ulcerative colitis and patients with Crohn's disease than in controls, and was significantly higher in patients with Crohn's disease compared with patients with ulcerative colitis. Age, gender, disease activity, extent of disease and small bowel involvement each did not affect ASCA levels. The use of elemental or polymeric diet therapy for Crohn's disease and administration of corticosteroids to patients with inflammatory bowel disease also did not affect ASCA levels. The ASCA titer was significantly lower in patients with Crohn's disease taking mesalazine than in those not taking it, although, serum IgG levels did not differ between these two groups, which might imply a suppression of IgG production by mesalazine at the intestinal level. CONCLUSIONS: The finding of increased serum ASCA titers in patients with inflammatory bowel disease suggests that Saccharomyces cerevisiae may play a role in the pathophysiology of this condition.