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J F Colombel

Publications and source records attributed to J F Colombel.

At least 19 recordsLinked to original sources
PubMed2000

Selective expansion of intraepithelial lymphocytes expressing the HLA-E-specific natural killer receptor CD94 in celiac disease.

BACKGROUND & AIMS: Celiac disease is a gluten-induced enteropathy characterized by the presence of gliadin-specific CD4(+) T cells in the lamina propria and by a prominent intraepithelial T-cell infiltration of unknown mechanism. The aim of this study was to characterize the subset(s) of intraepithelial lymphocytes (IELs) expanding during active celiac disease to provide insights into the mechanisms involved in their expansion. METHODS: Flow-cytometric analysis of isolated IELs and/or immunohistochemical staining of frozen sections were performed in 51 celiac patients and 50 controls with a panel of monoclonal antibodies against T-cell and natural killer (NK) receptors. In addition, in vitro studies were performed to identify candidate stimuli for NK receptor expression. RESULTS: In normal intestine, different proportions of IELs, which were mainly T cells, expressed the NK receptors CD94/NKG2, NKR-P1A, KIR2D/3D, NKp46, Pen5, or CD56. During the active phase of celiac disease, the frequency of CD94(+) IELs, which were mostly alphabeta T cells, was conspicuously increased over controls. In contrast, the expression of other NK markers was not modified. Furthermore, expression of CD94 could be selectively induced in vitro by T-cell receptor activation and/or interleukin 15, a cytokine produced by intestinal epithelial cells. CONCLUSIONS: The gut epithelium favors the development of T cells that express NK receptors. In active celiac disease, there is a specific and selective increase of IELs expressing CD94, the HLA-E-specific NK receptor that may be related to T-cell receptor activation and/or interleukin 15 secretion.

Adult↗
PubMed2000

Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy.

BACKGROUND & AIMS: Myelosuppression in patients with Crohn's disease (CD) treated with azathioprine has been attributed to low activity of thiopurine S-methyltransferase (TPMT). Allelic variants of the TPMT gene responsible for changes in the enzyme activity have been characterized. We investigated the distribution of mutant alleles associated with TPMT deficiency in patients with CD and myelosuppression during azathioprine/6-mercaptopurine therapy. METHODS: Forty-one patients with CD were included. They developed leukopenia or thrombocytopenia during azathioprine or 6-mercaptopurine treatment. Polymerase chain reaction-based methods were used to search for mutations associated with TPMT deficiency. RESULTS: Four patients (10%) had 2 mutant alleles associated with TPMT deficiency, 7 (17%) had 1 mutant allele, and 30 (73%) had no known TPMT mutation. The delay between administration of the drug and occurrence of bone marrow toxicity was less than 1.5 months in the 4 patients with 2 mutant alleles, and ranged from 1 to 18 months in patients with 1 mutant allele and from 0.5 to 87 months in patients with normal genotype. CONCLUSIONS: Twenty-seven percent of patients with CD and myelosuppression during azathioprine therapy had mutant alleles of the TPMT gene associated with enzyme deficiency. Myelosuppression is more often caused by other factors. Continued monitoring of blood cell counts remains mandatory in patients treated with azathioprine.

Adolescent↗
PubMed2000

Virus serology in familial Crohn disease.

BACKGROUND: Recent findings that early-in-life virus infections represent a risk factor for Crohn disease, that exacerbations of disease sometimes appear associated with common viral infections, and, in particular, suggestions that Crohn disease may be the result of persistent infection with measles virus prompted serologic studies for antibody to 19 common viruses, Chlamydia psittaci, and Mycoplasma pneumoniae. METHODS: Sera from 14 affected members of 2 French families with a high frequency of Crohn disease and from age- and sex-matched controls, taken in 1990 and 1992, and from unaffected family members were tested. Complement fixation, enzyme immunoassay, and indirect immunofluorescent tests were used. RESULTS: There were no significant differences between patients and controls or between affected and unaffected family members of family 2, with the exception that affected siblings carried higher antibody titers for mycoplasma one year and for varicella another year. There were no differences in measles IgM and IgG or mumps IgG antibody levels between patients and controls, or between patients and unaffected family members. CONCLUSIONS: Serology failed to find evidence of participation by 19 common viruses, C. psittaci, and M. pneumoniae in Crohn disease. The data do not support the hypothesis that persistent measles virus infection causes Crohn disease.

Adolescent↗
PubMed1999

Inflammatory alterations in mesenteric adipose tissue in Crohn's disease.

BACKGROUND & AIMS: Abnormalities of fat in the mesentery including adipose tissue hypertrophy and fat wrapping have been long recognized on surgical specimens as characteristic features of Crohn's disease. However, the importance, origin, and significance of the mesenteric fat hypertrophy in this chronic inflammatory disease are unknown. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a crucial factor involved in the homeostasis of adipose tissue, a major source of biologically active mediators. METHODS: Intra-abdominal fat accumulation was quantified using a magnetic resonance imaging method in patients with Crohn's disease and controls. PPARgamma and inflammatory cytokines synthesized by mesenteric adipose tissues were assessed by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. RESULTS: In vivo, patients with Crohn's disease have an important accumulation of intra-abdominal fat. This mesenteric obesity, present from the onset of the disease, is associated with overexpression of PPARgamma and tumor necrosis factor (TNF)-alpha, synthesized, at least in part, by adipocytes. CONCLUSIONS: These results suggest that confined increased PPARgamma mesenteric concentrations could lead to the mesenteric fat hypertrophy, which could actively participate through the synthesis of TNF-alpha in the inflammatory response.

Abdomen↗
PubMed1999

Acute inflammatory intestinal vascular lesions and in situ abnormalities of the plasminogen activation system in Crohn's disease.

OBJECTIVES: The distribution of the intestinal vascular lesions and their relation with the fibrinolysis process are poorly known in Crohn's disease (CD). The mediators of the plasminogen activator system, namely urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1), are a key complex involved in fibrinolysis. The aims of this study were: (1) to further define vascular lesions and their distribution in the intestine; and (2) to study concomitantly the qualitative in situ expression and the levels of u-PA, t-PA and PAI-1 in the ileum of patients with CD. PATIENTS AND METHODS: Histological, immunohistochemical and ultrastructural studies of vascular lesions in the resected ileum of 27 patients with CD were performed and compared with 36 control patients. Levels of u-PA, t-PA and PAI-1 measured by ELISA methods were compared in healthy and inflamed ileal tissues of 17 patients with CD. RESULTS: Acute vascular lesions involving mainly serosal venules and capillaries were present in 63% of patients with CD vs 3/36 controls and were associated with PAI-1 expression. They were prominent on the mesenteric border beneath macroscopically normal mucosa. In contrast, chronic vascular lesions were present in all layers beneath mucosal ulcerations, where a significant increase of PAI-1 levels was found. CONCLUSIONS: These results suggest that vascular involvement associated with abnormalities of PAI-1 expression is an early and widespread event in CD. Their prominence on the mesenteric border might explain the characteristic location of CD ulceration along the mesenteric margin.

Adolescent↗
PubMed1999

Alpha1-antitrypsin phenotypes and anti-neutrophil cytoplasmic auto-antibodies in inflammatory bowel disease.

OBJECTIVES: Alpha1-antitrypsin (alpha1-AT) is encoded by a highly polymorphic gene with over 75 codominantly expressed alleles at the protease inhibitor (Pi) locus classified as normal, deficient, dysfunctional or null. The aim of this study was to determine in patients with inflammatory bowel disease: (i) the prevalence of anti-neutrophil cytoplasmic auto-antibodies (ANCA) and their antigen specificities; (ii) alpha1-AT Pi phenotypes; and (iii) possible associations between ANCA, disease activity and deficient alpha1-AT alleles. DESIGN: Study of 95 consecutive patients with ulcerative colitis (UC) and 63 patients with Crohn's disease (CD). METHODS: Diagnosis and disease activity were determined by clinical, endoscopic and histological criteria. ANCA by indirect immunofluorescence (IIF) and Pi phenotyping by isoelectric focusing were performed for all patients. Positive IIF sera were tested in antigen-specific enzyme-linked immunosorbent assay: proteinase 3 (PR3), myeloperoxidase (MPO), lactoferrin (LF), lysozyme, human leucocyte elastase (HLE), cathepsin G and bactericidal/permeability increasing protein (BPI). RESULTS: Sixty-one patients with UC (64.2%) and only 11 with CD (17.5%) had ANCA (P < 0.001). Antigen specificities were PR3 (7/61), MPO (3/61), LF (6/61), HLE (1/63) and BPI (10/61) in UC, and PR3 (2/11) and BPI (2/11) in CD. Three PiZ alleles were found, matching the prevalence in the normal French control population. No relationship was found between the presence of ANCA, antibody specificity, disease activity and deficient alpha1-AT alleles. CONCLUSION: ANCA are more frequent in UC than CD and do not correlate with disease activity. ANCA and protease/antiprotease imbalance do not appear to modulate the clinical course of inflammatory bowel disease.

Alleles↗
PubMed1999

Abnormalities in mucin gene expression in Crohn's disease.

Alterations in the structure and/or quantity of mucins could alter the barrier function of mucus and play a role in initiating and maintaining mucosal inflammation in Crohn's disease. To investigate the hypothesis of a mucin gene defect in Crohn's disease, we analyzed the expression of the different mucin genes in the ileal mucosa of patients with Crohn's disease and controls. mRNA expression levels were assessed by a quantitative dot blot analysis and compared (i) between healthy and involved ileal mucosa of patients with Crohn's disease and (ii) between healthy mucosa of patients with Crohn's disease and controls. Expression of the different mucin genes was heterogeneous among controls and patients with Crohn's disease, except for MUC6 in controls. Nevertheless, MUC1 mRNA expression was significantly decreased in the involved ileal mucosa of patients with Crohn's disease when compared to the healthy mucosa (p = 0.02). Moreover, the expression levels of MUC3, MUC4, and MUC5B were significantly lower in both healthy and involved ileal mucosa of patients with Crohn's disease compared to controls (p < or = 0.05). The decrease of expression levels of some mucin genes (more particularly MUC3, MUC4, and MUC5B) in both healthy and involved ileal mucosa suggests a primary or very early mucosal defect of these genes in CD.

Adolescent↗
PubMed1999

Transdermal nicotine decreases mucosal IL-8 expression but has no effect on mucin gene expression in ulcerative colitis.

Our goal was to determine the effect of transdermal nicotine on cytokine and mucin gene transcription in ulcerative colitis (UC). Sixty-four nonsmoking patients with active UC were randomly assigned to transdermal nicotine (maximum dose 22 mg/day) or placebo for 4 weeks. Clinical assessment and colonic mucosal biopsies were obtained at entry and after 4 weeks. Inflammatory and immunoregulatory cytokines were assessed by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR). Based on this initial screen. IL-8 mRNA levels were measured by RT-competitive PCR. MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6 mRNA concentrations were measured by quantitative dot blot analysis. Cytokine mRNA expression, except for IL-8, was similar in all patients. IL-8 mRNA levels were significantly decreased in the colonic mucosa of nicotine-treated patients who improved (p = 0.04). IL-8 mRNA values were similar before and after treatment in nonresponding nicotine-treated patients and in all placebo-treated patients. Mucin gene expression was similar in all patient groups. Beneficial effects of transdermal nicotine in active UC may result from decrease of IL-8 expression at the transcriptional level. Transdermal nicotine has no effect on mucin gene transcription.

Administration, Cutaneous↗
PubMed1999

A controlled trial comparing ciprofloxacin with mesalazine for the treatment of active Crohn's disease. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID).

OBJECTIVE: The aim of this randomized controlled study was to investigate the efficacy of ciprofloxacin compared with mesalazine in treating active Crohn's disease. METHODS: Patients with a mild to moderate flare-up of Crohn's disease (mean Crohn's Disease Activity Index [CDAI]; 217; range, 160-305) were randomized to receive ciprofloxacin 1 g/day or Pentasa 4 g/day for 6 wk. Complete remission was defined at wk 6 as a CDAI < or = 150 associated with a decrease (delta) in CDAI > 75. Partial remission was defined as a CDAI < or = 150 with 50 < delta CDAI < 75 or a CDAI > 150 with delta CDAI > 50 at wk 6. Group sequential procedure with triangular continuation regions was used to monitor the trial through the difference in complete remission rates, every 20 patients included. RESULTS: Inclusion of patients was stopped at the second step, i.e., after 40 inclusions, with the conclusion of no difference in complete remission rates between ciprofloxacin- and Pentasa-treated groups. Among the 18 patients taking ciprofloxacin, two decided to stop treatment during the trial and three were considered as treatment failures because of deterioration at wk 3. Among the 22 patients taking mesalazine, one patient was lost to follow-up and eight patients were considered as treatment failures. Complete remission was observed in 10 patients (56%) treated with ciprofloxacin and 12 patients (55%) treated with mesalazine and partial remission was observed in three and one patient, respectively. CONCLUSIONS: This study suggests that ciprofloxacin 1 g/day is as effective as mesalazine 4 g/day in treating mild to moderate flare-up of Crohn's disease.

Adult↗
PubMed1999

Peroxisome proliferator-activated receptor gamma is induced during differentiation of colon epithelium cells.

Peroxisome proliferator-activated receptor gamma (PPARgamma), a fatty acid-activated nuclear receptor, is implicated in adipocyte differentiation and insulin sensitisation. In view of the association of dietary fat intake and bowel disease, the expression of PPARgamma in rodent and human intestine was studied. Expression of PPARgamma mRNA was examined by Northern blot hybridisation, RNase protection, and/or competitive RT-PCR assays, whereas PPARgamma protein levels were evaluated by immunoblotting and immunohistochemistry. PPARgamma mRNA and protein were abundantly expressed in colon relative to the small intestine both in rodents and in man. Interestingly, expression of PPARgamma was primarily localised in the more differentiated epithelial cells in the colon. The level of expression of PPARgamma in colon was similar to the levels seen in adipose tissue. Expression of PPARgamma increased from proximal to distal segments of the colon in man. In Caco-2 and HT-29 human adenocarcinoma cells, PPARgamma expression increased upon differentiation, consistent with PPARgamma being associated with a differentiated epithelial phenotype. High-level expression of PPARgamma was observed in the colon, but not in the small intestine, suggesting a potential role of this nuclear receptor in the colon.

Aged↗
PubMed1999

[Diffuse jejuno-ileitis of Crohn's disease: a separate form of the disease?].

BACKGROUND AND AIMS: Diffuse jejuno-ileitis of Crohn's disease may be a homogeneous clinical subgroup. The aim of this work was to compare the demographic and clinical data at diagnosis and the initial treatments of patients with diffuse jejuno-ileitis of Crohn's disease and to the ones without this localization. PATIENTS AND METHODS: For demographic and clinical studies, 48 (32M/16F) incident cases of diffuse jejuno-ileitis of Crohn's disease diagnosed between 1988 and 1994 in the EPIMAD register were compared with 96 (48M/48F) controls diagnosed the same year. As far as for the therapeutic management, the 48 incident cases were compared with 48 controls. RESULTS: Diffuse jejuno-ileitis constituted 3.3% of the total incident cases. Median age at diagnosis was significantly lower (20 vs 23 years, P = 0.01) and an upper digestive involvement was more frequent (56% vs 34%, P = 0.03) in patients with diffuse jejuno-ileitis. These patients were more often treated by total parenteral nutrition (43.8% vs 19.6%, P = 0.01) or azathioprine (50% vs 20.8%, P = 0.005). Azathioprine was also introduced earlier (20.7 vs 40.3 months, P = 0.009). Surgery for resection was less often required in diffuse jejuno-ileitis than in controls (65.2% vs 99.8%, P = 0.02) while more stricturoplasties were performed (52.9% vs 10%, P = 0.003); overall surgical rates did not significantly differ in the 2 groups. CONCLUSION: Our series suggest that diffuse jejuno-ileitis of Crohn's disease is a subgroup of patients characterized by a young age at diagnosis, with more frequent and earlier requirement for azathioprine.

Adolescent↗
PubMed1999

[Excluded rectum during Crohn's diseases: what is the risk of dysplasia?].

OBJECTIVES: An excluded rectum may be at risk of carcinoma in the course of Crohn's disease. Surveillance of patients requires detection of dysplasia. The aim of our study was to determine the frequency of dysplasia from secondary proctectomy specimens in active rectal Crohn's disease. METHODS: Twenty three patients (13 women and 10 men, median age 38 years) were studied. The median duration of rectal exclusion was four years. Detection of dysplasia relied upon histopathology. Immunohistochemistry with MIB-1 (Ki-67) and anti-p53 (clone DO7) antibodies was performed as well. RESULTS: Frequency of dysplasia was 30%. This was low grade dysplasia, focally observed in proctectomy specimens. MIB-1 was positive on 46% of dysplastic cells. There was no expression of p53 protein. CONCLUSIONS: These results must be taken into account for decision of secondary proctectomy, in patients having an excluded rectum for Crohn's disease, when ileorectal anastomosis is not possible. Rectal endoscopic surveillance is advisable with multiple biopsies according to focal distribution of dysplasia.

Adolescent↗
PubMed1998

Similar IL-5, IL-3, and GM-CSF syntheses by eosinophils in the jejunal mucosa of patients with celiac disease and dermatitis herpetiformis.

Celiac disease (CD) and dermatitis herpetiformis (DH) are gluten-sensitive diseases with different clinical features that can initiate similar intestinal changes. The flat-destructive stage corresponds to severe lesions involving activated T-cells. However, other inflammatory cells such as eosinophils are also abundant. The mechanisms for the intestinal recruitment of eosinophils in patients with CD and DH remain unknown. Eosinophil recruitment and activation are induced in vitro by three main cytokines: interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte-macrophage colony-stimulating factor (GM-CSF). In this study, IL-3, IL-5, and GM-CSF were detected by immunohistochemistry in all patients with CD and DH but not in the control group. By ultrastructural immunogold staining, these three cytokines had the same subcellular localization in the granule matrix of eosinophils. This result suggests that eosinophils may be involved in the immune response at the flat-destructive stage of both CD and DH.

Adolescent↗
PubMed1998

Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease.

BACKGROUND & AIMS: Infectious agents are suspected of being involved in the pathogenesis of Crohn's disease. This study was designed to look for the presence of virulent Escherichia coli strains associated with the ileal mucosa of patients with Crohn's disease. METHODS: E. coli strains were recovered from resected chronic ileal lesions (n = 20), neoterminal ileum after surgery from patients with (n = 19) and without (n = 11) endoscopic recurrence, and controls (n = 13). Bacterial adhesion was determined in vitro using intestinal cell lines; other associated virulence factors were assessed by DNA hybridization and polymerase chain reaction experiments. RESULTS: None of the strains harbored any of the virulence factor-encoding genes of E. coli involved in acute enteric diseases. However, mannose-resistant adhesion to differentiated Caco-2 cells was found for 84.6% and 78.9% of the E. coli strains isolated from chronic and early recurrent lesions, respectively, compared with 33% of controls (P < 0.02). In addition, 21.8% of the strains induced a cytolytic effect by synthesis of an alpha-hemolysin. CONCLUSIONS: E. coli strains isolated from the ileal mucosa of patients with Crohn's disease adhere to differentiated intestinal cells and may disrupt the intestinal barrier by synthesizing an alpha-hemolysin.

Adult↗