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PubMed1996

Neutrophil antibodies (pANCA) in chronic liver disease and inflammatory bowel disease: do they react with different antigens?

OBJECTIVE: A high frequency of perinuclear neutrophil antibodies (pANCA) has been described in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We evaluated the presence of pANCA in chronic liver disease and compared the immunoglobulin G (IgG) subclasses of pANCA in inflammatory bowel disease with chronic liver disease. Since the antigen reacting with pANCA could not be determined, the antigenic role of various neutrophil antigens was evaluated. SUBJECTS AND METHODS: Detection of pANCA and their IgG subclass was performed by immunofluorescence. One hundred and forty patients with chronic liver disease, 96 patients with inflammatory bowel disease and 40 healthy controls were tested for pANCA. pANCA positive and negative sera were evaluated for their reactivity with different neutrophil antigens in an enzyme-linked immunosorbent assay (ELISA) system. RESULTS: pANCA were found in 8 of 23 patients (35%) with autoimmune hepatitis, in 6 of 21 patients (28%) with primary biliary cirrhosis (PBC), in 18 of 25 patients (72%) with PSC, in 3 of 48 patients (6%) with viral hepatitis, in 30 of 48 patients (62%) with UC, and in 2 of 48 patients (4%) with Crohn's disease. All 20 patients with alcoholic liver disease and 40 healthy controls were negative for pANCA. In contrast to the patients with UC who had 83% IgG1 and only 13% IgG3 antibodies, patients with PSC and PBC had an overexpression of IgG3 antibodies (PSC: 50% IgG3; PBC: 67% IgG3). A proportion of pANCA positive sera recognized lactoferrin, myeloperoxidase, cathepsin G, laminarase and alpha 1-antitrypsin. CONCLUSION: pANCA is not present only in patients with UC but in autoimmune liver diseases such as PSC, autoimmune hepatitis and PBC. Considering the IgG subclass of pANCA, the antibody response of patients with UC is different from patients with liver disease. No unique pANCA specific antigen could be detected, so heterogeneity of pANCA has to be considered.

Adolescent↗

PubMed2000

Epstein-Barr virus-positive primary gastrointestinal Hodgkin's disease: association with inflammatory bowel disease and immunosuppression.

Inflammatory bowel disease (IBD) is associated with an increased risk of lymphoma, which is usually extraintestinal but sometimes may involve the diseased bowel itself. Most lymphomas described in this setting are of non-Hodgkin's type, but rare cases of Hodgkin's disease (HD) have been reported. We describe the clinicopathologic and molecular features of four patients with primary gastrointestinal HD. Three patients had preexistent Crohn's disease (CD), for which two of them had received immunosuppressive therapy. The fourth patient had a longstanding history of diverticulitis and myasthenia gravis and was receiving immunosuppressive therapy for the latter. Multifocal involvement of the bowel by HD was noted in all four cases. Disease was staged as IVA in one patient, IIIB in one patient, and IE in one patient, and the fourth patient died in the postoperative period before further workup. Two patients received chemotherapy, one of whom was dead at 9 months, whereas the other has no evidence of disease at 25 months' follow-up. The patient with IE disease did not receive any therapy because only a few microscopic foci of disease were present and is also without any evidence of disease at 17 months. The Reed-Sternberg (RS) cells in all four cases expressed CD30, CD15, EBER-1, and LMP-1; two of four were focally CD20-positive. VJ-polymerase chain reaction for immunoglobulin heavy chain (IgH) rearrangement showed a polyclonal pattern in all four cases. In two cases, laser capture microdissection was used to isolate individual RS and Hodgkin's cells, which contained rearranged immunoglobulin genes, confirming a B-cell genotype. Whereas one case showed a dominant clonal band present in all isolates, cells from the patient with stage IE disease clearly showed a polyclonal population of RS cells. Our findings indicate that HD arising in the setting of IBD or chronic inflammation is the result of an Epstein-Barr virus-driven lymphoproliferation, analogous to that found in other immunodeficient states. Disordered immunoregulation inherent to CD and immunosuppressive therapy for the latter may contribute to its development. The finding of polyclonal RS cells in a patient with early stage disease and apparent cure by surgical resection versus monoclonal RS cells in the patient with disseminated disease suggests that HD in the setting of immunodeficiency also may show molecular progression, in a manner similar to that occurring in conventional B-cell lymphoproliferative disorders arising in the same setting.

Adult↗

PubMed2006

Inflammatory bowel disease after liver transplantation: risk factors for recurrence and de novo disease.

Inflammatory bowel disease (IBD) is associated with primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) and can recur or develop de novo after orthotopic liver transplantation (OLT). The aim of this study was to investigate the incidence and severity of IBD after liver transplantation and to perform a multivariate analysis for possible risk factors. In this retrospective study, 91 patients transplanted for PSC or AIH, without prior colectomy, were included. Sixty patients were transplanted for PSC, 31 for AIH. IBD activity before and after OLT and other possible risk factors were analysed in a multivariate model. Forty-nine patients (54%) had IBD before OLT. Forty patients (44%) had active IBD after transplantation: recurrence in 32 and de novo in 8. Cumulative risk for IBD after OLT was 15, 39 and 54% after 1, 5 and 10 years, respectively. In 59% of patients with IBD prior to OLT the disease was more active after transplantation. Risk factors for recurrent disease were: symptoms at time of OLT, short interval of IBD before OLT and use of tacrolimus. 5-aminosalicylates were protective. A cytomegalovirus positive donor/negative recipient combination increased the risk for de novo IBD.

Adult↗

PubMed2001

Unusual presentation of Hodgkin's disease mimicking inflammatory bowel disease.

A case of a 32-years old man with a long lasting history of inflammatory bowel disease (IBD) is described. He was treated in the past with adequate medical therapy with considerable improvement of the symptoms. However, after the resolution of the last episode of abdominal pain and diarrhoea, because of multiple protruding masses and sub-stenotic regions found during a colonoscopy, the patient underwent a right enlarged hemicolectomy with jejunal resection. During the surgical procedure 16 enlarged lymphnodes were removed. The histological examination of the surgical specimen showed the presence of numerous Reed-Sternberg cells, compatible with a diagnosis of Hodgkin's disease (HD). None of the removed lymphnodes showed the presence of tumor cells, and in addition the systemic staging procedure was negative. After staging, the ABVD regimen was started, achieving a complete clinical and pathological response. This is a rare case of primary extranodal HD localized to the colon, in a patient with a long standing history of IBD, who showed an optimal response to chemotherapy. The case and the differential diagnosis with other pathological entities of the bowel is discussed.

Adult↗

PubMed2001

[Initial experience with detection of Saccharomyces cerevisiae antibodies in patients with primary nonspecific inflammatory bowel disease].

INTRODUCTION: Inflammatory bowel diseases (IBD), with Crohn's disease (CD) and ulcerative colitis (UC) as the two main disorders, is a heterogeneous group of diseases of unknown etiology. Actually we have no ideal disease marker, to identify people at risk of the disease, which can differentiate CD from UC, be highly specific for CD or UC and easily applicable in routine laboratory praxis. AIMS: Determine the clinical significance of serological testing p-ANCA and ASCA in patients with IBD. METHODS: P-ANCA in IgG isotype were detected by indirect fluorescence assay on human ethanol-fixed granulocytes, ASCA antibodies in IgG and IgA isotypes were determined by ELISA with mannan as a target antigen. RESULTS: P-ANCA and ASCA were studied in a group of 86 patients (38 CD, 26 UC, 3 non-inflammatory gastrointestinal disorder, 19 health controls). P-ANCA was associated with UC in 46%. ASCA was associated with CD in 76%. Specificity of ANCA for UC compared to healthy controls was 100%, specificity of ASCA for CD compared to healthy controls was 89.5%. CONCLUSION: Although the sensitivity of ASCA and p-ANCA is low, their specificity is high, especially when combining these two markers. We think that combined assay for ASCA and p-ANCA is more useful in IBD.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2001

Neuronal COX-2 expression in human myenteric plexus in active inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with changes in colonic motility which may contribute to the pain and diarrhoea associated with exacerbations of this disease. These changes may be mediated by prostaglandins which are increased in this condition. Increased expression of the inducible isoform of cyclo-oxygenase (COX-2) has been found in active IBD although its cellular distribution remains uncertain. AIMS: To evaluate the cellular distribution of COX-2 in active IBD. PATIENTS AND METHODS: Using reverse transcription-polymerase chain reaction, in situ hybridisation, and immunohistochemistry, COX-2 expression was evaluated in 12 colectomy specimens from patients with active ulcerative colitis (UC), and six specimens from patients with Crohn's colitis that had failed medical therapy. Histologically normal colon was obtained from 12 patients having resection for colorectal neoplasia and evaluated as above, acting as control specimens. RESULTS: All specimens expressed COX-2 mRNA, with some 6-8-fold increase in inflamed tissues on densitometric analysis (both UC and Crohn's) compared with controls. In situ hybridisation localised this mRNA to myenteric neural cells, surrounding smooth muscle cells, and inflammatory cells of the lamina propria in the IBD specimens, with some weaker labelling seen in the epithelium. No COX-2 labelling was seen in normal tissues. Immunohistochemistry confirmed these sites of COX-2 expression in all inflamed specimens, with absence of immunoreactivity in control tissues. CONCLUSIONS: These findings provide the first evidence of COX-2 expression in neural cells of the myenteric plexus in active IBD which, via increased prostaglandin synthesis at this site, may contribute to the dysmotilty seen in this condition.

Adult↗

PubMed2006

Inflammatory bowel diseases.

The inflammatory bowel diseases remain at the forefront of clinical investigation. Immunologic and genetic advances are fueling an explosion of novel diagnostic and therapeutic modalities. With further breakthroughs, there is hope that in the near future, these illnesses will no longer be considered either idiopathic or chronic.

Adult↗

PubMedDate not supplied

[Quality of life assessment in Inflammatory Bowel Disease (IBD): German version of the Inflammatory Bowel Disease Questionnaire (IBDQ-D; disease-specific instrument for quality of life assessment) -- first application and comparison with international investigations].

BACKGROUND: Health-related quality of life (HRQOL) is an important outcome-parameter in health research and care. The aim of the working group Quality of Life in the Competence Network Inflammatory Bowel Disease (IBD; in the original German: "Kompetenznetz chronisch entzündliche Darmerkrankungen") is to generate instruments for assessment of HRQOL and its implementation as standards in clinical trials, health care and research in IBD. METHODS: The Inflammatory Bowel Disease Questionnaire (IBDQ) is an international validated disease specific instrument for HRQOL-assessment. A German version of the IBDQ was elaborated and tested in 415 outpatients with Crohn's disease (CD, n = 306) and ulcerative colitis (UC, n = 109). The aim of the study was to compare the results of HRQOL-assessment (IBDQ-D) with international investigations, to correlate HRQOL results with disease activity and to preform a pretest of psychometric properties. RESULTS: International data suggest that the IBDQ-D is a suitable instrument for HRQOL-assessment in CD and UC. For both disease a statistically significant negative correlation with disease activity was found. Tested psychometric properties do not suggest that a revision of the IBDQ-D is required. The IBDQ-D offers the HRQOL-assessment as an primary or secondary outcome in clinical trials in IBD in Germany.

Adult↗

PubMed1988

Inverse relationship between colonic (Na+ + K+)-ATPase activity and degree of mucosal inflammation in inflammatory bowel disease.

In inflammatory bowel disease (IBD), mucosal damage and loss of colonic function are regarded as major consequences of inflammation. Decreased colonic (Na+ + K+)-ATPase activities with diminished reabsorption of sodium and water have been found in active stages of ulcerative colitis. In this study, we report an inverse relationship between colonic (Na+ + K+)-ATPase activity and the degree of mucosal inflammation in 19 patients with IBD of mild to moderate disease activity. Various macroscopic and histologic types of mucosal lesions were differently associated with the (Na+ + K+)-ATPase activities. 5'-nucleotidase activity was not associated with the degree of mucosal inflammation or the kind of macroscopic or histologic lesions. Our findings support the view that, in contrast to 5H-nucleotidase, (Na+ + K+)-ATPase activity may better reflect the severity of mucosal damage and the degree of inflammation in IBD.

5'-Nucleotidase↗

PubMed1997

Synergistic effect of immunoregulatory cytokines on peripheral blood monocytes from patients with inflammatory bowel disease.

Active inflammatory bowel disease (IBD) is characterized by increased monocyte secretion of proinflammatory cytokines. Immunoregulatory cytokines such as Interleukin (IL)-4, IL-10, and IL-13 are capable of inhibiting the proinflammatory cytokine response of activated monocytes. The aim of our study was to determine the effect of different antiinflammatory cytokines under various culture conditions and to evaluate combinations of antiinflammatory cytokines in down-regulating monocyte response in IBD. Peripheral monocytes from patients with active IBD were isolated and stimulated with pokeweed mitogen (PWM). IL-4, IL-10, IL-13 and a combination of IL-4/IL-10 and IL-10/IL-13 were added at different concentrations and different times. Secretion of IL-1beta and TNF-alpha was assessed using sandwich ELISA systems. There was a diminished down-regulation of TNF-alpha by IL-4 and IL-13 in IBD when the cytokines were added at the time of stimulation, while there was a significantly higher down-regulation when monocytes were primed with these Th-2 cytokines 24 hr before activation. IL-10 plus IL-4 and IL-10 plus IL-13, respectively, inhibited the proinflammatory cytokine response of monocytes as well as matured macrophages much more than IL-4, IL-10, or IL-13 alone. Even at suboptimal concentrations for each cytokine alone, a combination of cytokines showed synergistic inhibitory effects. In summary, a combination of antiinflammatory cytokines is more effective in down-regulating the response of activated monocytes than using the cytokines alone and thus may have a potential therapeutic benefit for patients with IBD.

Cells, Cultured↗

PubMed1998

Association of HLA class-II genes and anti-neutrophil cytoplasmic antibodies in Chinese patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is common in the West but rare in China. The genetic factor predisposing to the disease is unclear. Ulcerative colitis (UC) is found to be associated with HLA DR2 alleles in the West. Subgroups of UC patients have been further defined by the presence of anti-neutrophil cytoplasmic antibodies (ANCA). METHODS: We attempted to define the HLA class-II genes (DRbeta, DQalpha, DQbeta) and their relationship with ANCA in southern Chinese patients with UC. Patients were tested for class-II genes by restriction fragment length polymorphism and polymerase chain reactions. The indirect immunofluorescence test was used to detect ANCA in the sera. Ethnically matched normal controls were used for comparison. RESULTS: In ANCA-positive UC patients (n = 18) there was a strong association with HLA-DQalpha1c allele (P < 0.0001) when compared with controls (n = 104). This association was not found in ANCA-negative UC patients (n = 10) (P = 0.21). CONCLUSIONS: In Chinese UC patients positive ANCA is associated with the HLA-DQalpha1c allele, which is not the case in Caucasian patients.

Adult↗

PubMed2006

Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases.

BACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by a breakdown of colon epithelial barrier function. Antimicrobial peptides like cathelicidins are molecules of the innate immune system located at epithelial surfaces. Cathelicidins influence microbial growth and inflammation and may play a role in IBD. In this study, the expression of human cathelicidin hCAP18/LL-37 was investigated in the intestinal mucosa from patients suffering from ulcerative colitis or Crohn's disease. METHODS: Biopsy material from colon and ileal mucosa of a total of 89 patients (34 with Crohn's disease, 27 with ulcerative colitis, 28 control patients) was evaluated for cathelicidin expression by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. Colon epithelial cells were stimulated in vitro with various cytokines to evaluate mechanisms that influence cathelicidin production. RESULTS: Cathelicidin expression was significantly increased in inflamed and non-inflamed colon mucosa from ulcerative colitis patients compared to non-inflamed control mucosa. In patients with Crohn's disease cathelicidin expression was not changed in inflamed or non-inflamed colon or ileal mucosa independent of NOD2 status. Biopsies evaluated by immunohistochemistry showed epithelial cathelicidin expression in the upper crypt that was diffuse in controls and only basal in IBD patients. Inflammation mediators, alone or in combination with the known cathelicidin inducer butyrate, had no effect on cathelicidin expression in cultured colon cells. CONCLUSIONS: In IBD the colonic expression of human cathelicidin is altered: cathelicidin expression is increased in inflamed and non-inflamed mucosa in patients suffering from ulcerative colitis but not in Crohn's disease. This deficiency may further compromise the antimicrobial barrier in Crohn's disease.

Adult↗

PubMedDate not supplied

Antibody secretion by human intestinal mononuclear cells from normal controls and inflammatory bowel disease patients.

Inflammatory bowel disease (IBD) intestinal mononuclear cells (MNC) exhibit decreased spontaneous IgA secretion with an increased percentage of monomeric IgA and IgA subclass 1 in both ulcerative colitis and Crohn's disease patients. When compared with control intestinal MNC, a marked increase in spontaneous secretion of IgG is observed from IBD MNC. The greatest increase in spontaneous IgG secretion is seen with ulcerative colitis intestinal MNC, due to the secretion of large amounts of IgG subclass 1. Crohn's disease intestinal MNC have increased IgG subclass 2 secretion. Similar differences in IgG subclass concentrations also occur in the sera of active, untreated, IBD patients. Therefore, major alterations occur with regard to spontaneous antibody secretion of IgA and IgG subclasses in IBD. Because intestinal MNC comprise a unique immunologic compartment, it will be important to better understand the regulatory mechanisms, effector capabilities, and inducing antigens involved in intestinal IgA and IgG subclass secretion in IBD.

Antibody Formation↗

PubMed1986

Surgical management of nonspecific inflammatory bowel disease.

Nonspecific inflammatory bowel disease is principally represented by Crohn's disease and ulcerative colitis. This article reviews the radical changes in the surgical treatment of these conditions that may avert life-threatening situations and dramatically improve the quality of life.

Colitis, Ulcerative↗

PubMed1985

Psoas abscess in inflammatory bowel disease.

The inflammatory bowel disease (IBD) is sometimes complicated by the development of a psoas abscess. We recently encountered three patients of IBD with psoas abscess. Two patients had Crohn's ileocolitis and one with ulcerative colitis. During 1979-1984, 23 patients with psoas abscess due to a variety of underlying disease processes were seen at our institution. At the same time period, 483 cases of Crohn's disease and 283 cases of ulcerative colitis were encountered. Therefore, of 766 patients with IBD only three were complicated by psoas abscess (incidence ratio = 0.6%). Thus, psoas abscess was a very rare complication of IBD in patients seen at our institution. In our series of 23 psoas abscess patients, IBD was not a major causative factor. Additionally, to our knowledge, psoas abscess complicating ulcerative colitis has not been reported previously.

Abscess↗

PubMed2002

The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease.

BACKGROUND & AIMS: Mutations in the NOD2 gene are strongly associated with susceptibility to Crohn's disease (CD). We analyzed a large cohort of European patients with inflammatory bowel disease to determine which mutations confer susceptibility, the degree of risk conferred, their prevalence in familial and sporadic forms of the disease, and whether they are associated with site of disease. METHODS: Individuals were genotyped for 4 NOD2 mutations: P268S, R702W, G908R, and 3020insC. Allelic transmission distortion to 531 CD- and 337 ulcerative colitis-affected offspring was assessed by the transmission disequilibrium test. Association was also tested in an independent cohort of 995 patients with inflammatory bowel disease and 290 controls. Cases were stratified by disease site and compared across NOD2 genotypes. RESULTS: R702W, G908R, and 3020insC were strongly associated with CD but not with ulcerative colitis. Linkage disequilibrium was observed between P268S and the other mutations, forming 3 independent disease haplotypes. Genotype relative risks were 3.0 for mutation heterozygotes and 23.4 for homozygotes or compound heterozygotes. The frequency of NOD2 mutations was higher in cases from families affected only with CD and was significantly increased in ileal-specific disease cases compared with colon-specific disease (26.9% vs. 12.7%, P = 0.0004). CONCLUSIONS: The R702W, G908R, and 3020insC mutations are strong independent risk factors for CD and are associated particularly with ileal disease.

Carrier Proteins↗

PubMedDate not supplied

Perinuclear antineutrophilic cytoplasmic antibody and response to treatment in diarrheic dogs with food responsive disease or inflammatory bowel disease.

The goal of this study was to investigate the correlation between perinuclear antineutrophilic cytoplasmic antibody (pANCA) and clinical scores before and after treatment in diarrheic dogs with food-responsive disease (FRD) or inflammatory bowel disease (IBD). pANCA serology was evaluated prospectively by indirect immunofluorescence in 65 dogs with signs of gastrointestinal disease, and if positive, pANCA antibody titers were determined. Thirty-nine dogs with FRD responded to a novel diet, and 26 dogs with IBD were treated with corticosteroids. The severity of clinical signs was scored by means of a canine IBD activity index (CIBDAI). At initial examination, a significantly (P = .002) higher percentage of dogs were pANCA-positive in the FRD group (62%) compared with the IBD group (23%). pANCA titers were significantly higher (P = .003) before treatment in the FRD group (median titer 100) compared with the IBD group (median titer 1). However, there was no difference in pANCA titers between the groups after respective treatments because dogs in the IBD group had a significant increase in pANCA titer after treatment. The CIBDAI score decreased significantly (P < .001) after treatment in both groups (74% moderate to severe in FRD dogs before versus 8% after treatment; 85% moderate to severe in IBD dogs before versus 32% after treatment). There was no correlation between pANCA status in FRD or IBD dogs before treatment and scores for CIBDAI, endoscopy, or histopathology before or after treatment, except for the endoscopic duodenal score in dogs with FRD after treatment (P = .03). A positive pANCA test before therapy may aid in the diagnosis of FRD.

Animals↗

PubMed1998

[Diagnosis in chronic inflammatory bowel diseases--report of the Austrian Chronic Inflammatory Bowel Disease Study Group].

Diagnostic procedures in inflammatory bowel diseases (IBD) serve to secure the diagnosis and to optimize treatment. Upon initial diagnosis endoscopy up to the terminal ileum is mandatory including multiple step biopsies. When diagnostic guidelines are followed and adequate clinical information is available, IBD will be correctly classified in about 80 to 90% of cases upon first examination. In contrast endoscopic studies are only of limited value in monitoring treatment. The decision if and when to perform endoscopy during exacerbation of disease must be an individual one. When disease activity is evaluated, a distinction must be made between degree of activity as reflected by laboratory parameters and severity of illness as reflected by the clinical presentation with abdominal complaints, fistulas, abscesses, etc. Distinct activity indices are useful in clinical studies to obtain an objective evaluation of activity and severity of disease. At clinical routine visits questions should not only concern the basic illness but also ask for quality of life and psychosocial status. Only a small number of laboratory tests are needed for basic diagnosis and follow-up. A small bowel enteroclysis should always be performed upon primary diagnosis of Crohn's disease and during the course of disease when there is suspicion of small-bowel involvement. Double contrast barium enema should be limited to special indications as incomplete colonoscopy e.g. due to stenosis or suspected fistula. Sonography is the primary investigation when complications are suspected. CT is useful as an adjunct or when the afore mentioned methods do not show clear findings. NMR is the procedure of choice for detection of pararectal fistulas and abscesses. Transrectal endosonography is comparably good but limited to the experience of the investigators and by patient's tolerability.

Biopsy↗