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J F Colombel

Publications and source records attributed to J F Colombel.

At least 91 records · Page 5Linked to original sources

Anti-Saccharomyces cerevisiae mannan antibodies in familial Crohn's disease.

OBJECTIVE: Anti-Saccharomyces cerevisiae mannan antibodies (ASCA) are associated with Crohn's disease. The aim of this study was to determine the prevalence of ASCA in families in which at least two members were affected with Crohn's disease. METHODS: A total of 20 families including two (n=15) or more (n=5) patients with Crohn's disease were tested for ASCA with use of an ELISA method. Overall, 51 affected members, 66 healthy first degree relatives, and 163 healthy control subjects were studied. RESULTS: ASCA were detected in 35 of 51 (69%) patients with Crohn's disease and in 13 of 66 (20%) healthy relatives versus one of 163 healthy control subjects (p < 0.0001 and p < 0.001). ASCA-positive relatives were distributed in 12 of 20 families. ASCA were present in eight healthy parents and four healthy siblings. The prevalence of ASCA in relatives did not depend on the ASCA status of affected members. CONCLUSION: ASCA in 20% of healthy first degree relatives of patients with Crohn's disease suggest that these antibodies might be a subclinical marker for Crohn's disease in families. Whether ASCA reflect environmental or genetic factors or a combination of both is unknown.

Adolescent↗

Abnormal mucus in cap polyposis.

BACKGROUND: Cap polyposis is a rare disease characterised by mucoid and bloody diarrhoea, with polyps covered by a cap of mucoid and fibrinopurulent exudate. The pathogenesis is not known. AIMS: To pour some light on cap polyposis pathogenesis, by examining the mucus of patients and analysing the expression of five mucin genes, MUC2, MUC3, MUC4, MUC5AC, and MUC5B. PATIENT AND METHODS: The study was performed on biopsy specimens taken from a patient with recurrent cap polyposis. Histochemical examination, electron microscopy, and mRNA in situ hybridisation were used. RESULTS: The mucus of cap polyposis differed in three respects from that of normal adult colon: abnormal ultrastructure of the mucus in the goblet cells, predominance of non-sulphated mucins, abnormal expression of the MUC4, MUC3, and MUC5AC genes. CONCLUSIONS: Most of these abnormalities have been reported for other pathological situations, suggesting that the abnormalities observed in the mucus of this patient with cap polyposis are probably secondary phenomena rather than primary. However, the mucin abnormalities detected, which reflect deregulation of the expression of three apomucin genes, abnormal glycosylation, and abnormalities of the secretion process, are also probably involved in the clinical manifestations of cap polyposis.

Adult↗

Anticipation in familial Crohn's disease.

BACKGROUND: Offspring with a family history of Crohn's disease have an earlier age of onset than their parents. This might be due to genetic anticipation, characterised by earlier and/or more severe disease in subsequent generations. AIMS: To investigate the possibility of genetic anticipation in affected parent-child pairs with Crohn's disease from France and Belgium. PATIENTS AND METHODS: In a cohort of 160 multiply affected families with Crohn's disease, 57 parent-first affected child pairs were detected. Clinical characteristics (age at diagnosis, disease extent, and type) of both parents and children were registered and compared. RESULTS: Children were younger than their parents at diagnosis in 48/57 (84%) pairs. The median age at diagnosis was 16 years younger in children than in parents (p < 0.0001). However, the difference was related to the age at diagnosis in the parents and was not present in 12 parent-child pairs with an early age at diagnosis for the parents. In most cases, disease extent and type were not considered more severe in children than in parents. Parental sex affected neither age at diagnosis nor extent and type of disease in children. CONCLUSION: Patients in the second affected generation acquire their disease at an earlier time in life in some but not all familial cases of Crohn's disease. Several explanations including genetic anticipation and environmental factors might explain this phenomenon.

Adolescent↗

Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role.

BACKGROUND: Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) are a well recognised marker for ulcerative colitis. Antibodies to oligomannosidic epitopes of the yeast Saccharomyces cerevisiae (ASCA) are a new marker associated with Crohn's disease. AIMS: To assess the value of detecting pANCA and/or ASCA for the diagnosis of ulcerative colitis and Crohn's disease. METHODS: Serum samples were obtained from 100 patients with Crohn's disease, 101 patients with ulcerative colitis, 27 patients with other miscellaneous diarrhoeal illnesses, and 163 healthy controls. Determination of pANCA and ASCA was performed using the standardised indirect immunofluorescence technique and an ELISA, respectively. RESULTS: The combination of a positive pANCA test and a negative ASCA test yielded a sensitivity, specificity, and positive predictive value of 57%, 97%, and 92.5% respectively for ulcerative colitis. The combination of a positive ASCA test and a negative pANCA test yielded a sensitivity, specificity, and positive predictive value of 49%, 97%, and 96% respectively for Crohn's disease. Among patients with miscellaneous non-inflammatory bowel disorders, three were ASCA positive and two were pANCA positive. One control was ASCA positive. The presence of ASCA in patients with Crohn's disease was associated with small bowel involvement. CONCLUSION: ASCA and pANCA are strongly associated with Crohn's disease and ulcerative colitis, respectively. Combination of both tests could help the diagnosis of inflammatory bowel disease.

Adult↗

Evidence of linkage of the inflammatory bowel disease susceptibility locus on chromosome 16 (IBD1) to ulcerative colitis.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) of unknown aetiology which are characterised by chronic inflammation of the gastrointestinal tract. Epidemiological studies suggest the presence of a genetic component in the aetiology of both CD and UC. A susceptibility gene for Crohn's disease has recently been mapped to the pericentromeric region of chromosome 16 (IBD1), and this finding has been replicated in two subsequent studies. Although CD and UC are distinct clinical entities, the fact that both disorders occur in a significant proportion of families with multiple cases of IBD suggests that overlapping sets of susceptibility genes may be involved. We have addressed this question for IBD1 by typing eight microsatellite markers from the locus in 70 kindreds affected with either UC only or with both UC and CD and analysing the data for linkage by both non-parametric and parametric methods. Evidence for linkage was detected in families affected with only UC, with a mean proportion of 0.70 affected sib pairs sharing alleles identical by descent at D16S3136 (p=0.01), and a peak non-parametric linkage score of 2.02 at D16S3120 with the GENEHUNTER program (p=0.02). The estimated sib relative risk attributable to IBD1 in these families was 1.46. Surprisingly, no evidence of linkage was detected in the families affected with both UC and CD (p>0.2). The data suggest that IBD1 may also contribute to susceptibility to ulcerative colitis, and that it is likely to be located in the 12 cM interval between D16S419 and D16S409.

Chromosomes, Human, Pair 16↗

[The synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, a rare extra-digestive manifestation of Crohn's disease. Presentation of 1 case and review of the literature].

We report the case of a 33-year-old man with a severe Crohn's disease since the age of sixteen. He presented with acne and palmoplantar pustulosis associated with a right knee synovitis. Investigations revealed a major axial bone condensation. The association synovitis-acne-pustulosis-hyperostosis-osteitis leaded to the diagnosis of SAPHO syndrome associated with Crohn's disease.

Acne Vulgaris↗

Circulating growth-regulator oncogene alpha contributes to neutrophil priming and interleukin-8-directed mucosal recruitment into chronic lesions of patients with Crohn's disease.

Crohn's disease (CD) lesions are characterized by a marked neutrophilic infiltrate associated with enhanced mucosal IL-8, contrasting with low serum IL-8 levels. The aim of this study was to investigate the effects of circulating GROalpha and IL-8 on neutrophil priming and migration. The expression of surface molecules involved in rolling (CD62L, CD15) and firm adhesion (Mac-1 and LFA-1) to endothelial cells was assessed by flow cytometry, while the chemotactic response of PMN to IL-8 and to fMLP was investigated in a Boyden chamber assay. In addition, IL-8 and GROalpha levels were determined by ELISA in plasma samples and in culture supernatants of purified polymorphonuclear neutrophils (PMN) and peripheral blood mononuclear cells (PBMC) from patients with CD and healthy blood donors. This study revealed an upregulation of CD11b (Mac-1) membrane expression on circulating PMN from patients with CD, as assessed by the mean fluorescence intensity which reflects antigen density. Furthermore, an enhanced chemotactic response towards both fMLP and IL-8 of PMN from CD patients was observed. Despite often undetectable levels of circulating IL-8, all plasma samples were positive for GROalpha, with a significant increase in CD patients when compared to donors. In vitro, equivalent concentrations of GROalpha were able to increase the IL-8 driven chemotaxis of PMN. In conclusion, blood PMN from patients with CD showed an enhanced capacity to be recruited into inflammed intestinal mucosa, which could be due to an increased expression of CD11b (Mac-1) as well as an increased chemotactic response toward fMLP or IL-8. This priming effect of PMN in CD may partly occur through elevated circulating GROalpha levels.

Case-Control Studies↗

Distinct cytokine patterns in early and chronic ileal lesions of Crohn's disease.

BACKGROUND & AIMS: Chronic intestinal lesions of patients with Crohn's disease (CD) are associated with a T helper (Th) 1-type cytokine profile, including high levels of interleukin 2 (IL-2) and interferon gamma (IFN-gamma). However, the mechanisms involved in the pathogenesis of the early mucosal lesions are poorly known. The aim of this study was to examine the pattern of Th1- and Th2-type (IL-4, IL-5, and IL-13) cytokines in the early ileal lesions occurring in patients with CD 3 months after ileal resection and ileocolonic anastomosis. Cytokines were also examined in the chronic ileal lesions to look for cytokine patterns related to disease progression. METHODS: Ileal biopsy specimens were obtained from 17 patients with CD and 11 controls. Mucosal IL-2, IFN-gamma, IL-4, IL-5, and IL-13 messenger RNA (mRNA) was evaluated by competitive reverse-transcription polymerase chain reaction. RESULTS: The early ileal lesions of patients with CD were associated with a significant increase of IL-4 mRNA and a decrease of IFN-gamma mRNA compared with the normal mucosa of patients with CD or controls. A Th1-type pattern was observed in the chronic ileal lesions. CONCLUSIONS: Divergent cytokine patterns are observed during different clinical stages of CD. These observations need to be considered in the development of newer specific therapeutic agents to prevent CD recurrences.

Adult↗

Immunoglobulin G subclass distribution of anti-endothelial cell antibodies (AECA) in patients with ulcerative colitis or Crohn's disease.

Anti-endothelial cell antibodies have been described in sera from patients with inflammatory bowel disease. The aim of this study was to determine, by ELISA, the IgG subclass distribution of anti-endothelial cell antibodies, in patients with ulcerative colitis (N = 28) or Crohn's disease (N = 82) as compared with blood donors (N = 95). Thirty-six percent of ulcerative colitis and 23% of Crohn's disease patients were positive for at least one of the IgG anti-endothelial cell subclasses. Interestingly, the pattern of IgG anti-endothelial cell subclass observed in the two inflammatory bowel diseases differs. In Crohn's disease, the IgG1 anti-endothelial cell antibody level was significantly increased (P < 0.05) while IgG2 and IgG4 anti-endothelial cell antibody levels were decreased (P < 0.0001 and P < 0.01, respectively) as compared to ulcerative colitis patients. The immunoglobulin G3 anti-endothelial cell antibody level was decreased in both ulcerative colitis and Crohn's disease patients as compared to healthy blood donors. No relationship was detected between disease activity of ulcerative colitis or Crohn's disease patients and anti-endothelial cell IgG subclasses. Finally, the disparity of IgG anti-endothelial cell subclass distribution in these two inflammatory bowel diseases suggests that the ability to activate effector mechanisms is not identical, and hence, deals with the concept of distinctive pathogenetic mechanisms in these two diseases.

Adolescent↗

Fecal beta-D-galactosidase production and Bifidobacteria are decreased in Crohn's disease.

Digestive bacterial microflora play a major role in the pathogenesis of Crohn's disease (CD). Bacterial enzyme activities, especially beta-D-galactosidase, are decreased in fecal extracts from CD patients. We hypothesized that an alteration of the colonic flora might be responsible for this decrease. Indeed, we demonstrate that beta-D-galactosidase production in supernates of anaerobic cultures was significantly (P < 0.01) reduced in feces from patients with active Crohn's disease (N = 7), when compared to healthy controls (N = 8). Therefore using X-gal and selective media, we enumerated bacteria able to release beta-D-galactosidase in feces from patients with active (N = 16) or quiescent disease (N = 5) and healthy controls (N = 14). Bifidobacteria numbers were significantly reduced in patients (P < 0.01 for active; P < 0.02 for quiescent disease) whereas Bacteroides and Lactobacilli counts remained unchanged. beta-D-Galactosidase activity and Bifidobacteria counts were significantly correlated (P < 0.03). Bifidobacteria are regarded as beneficial for the host. The reduction in Bifidobacteria is responsible for decreased beta-D-galactosidase activity. Thus oral administration of prebiotics that promote their growth might have potential therapeutic interest.

Adolescent↗

Nitrate-reducing bacteria in diversion colitis: a clue to inflammation?

A pathogenic role of nitric oxide has been suggested in acute and chronic intestinal inflammation. We took the opportunity offered by studies in patients with excluded colon, which represents a model of chronic intestinal inflammation with no exogenous nitrite or nitrate supply, to evaluate the quantity and the quality of nitrate reducers in diversion colitis. Thirty patients (17 men, 13 women, mean age 45 years) having an excluded colon for various reasons were sampled by rectal swabs and compared to 30 healthy controls (11 men, 19 women, mean age 28 years). The percentage of nitrate-reducers among the total count of subcultured bacteria was 46 +/- 41% (mean +/- SD) in patients with diversion colitis as compared to 19 +/- 24% in healthy controls. This difference was significant (P < 0.05) despite great heterogeneity in individual values. In patients with diversion colitis, 75/254 (29.5%) different isolated bacterial strains were nitrate-reducers as compared to 61/294 (21%) (P < 0.05) in controls. Among the 75 nitrate-reducing strains isolated from patients with diversion colitis, 55 were aerobes. Pseudomonas species were only encountered in this population. The predominant group was enterobacteria with a high isolation rate of species belonging to the genera Proteus, Providencia, and Morganella. In healthy controls nitrate-reducing anaerobes were nearly as frequent as aerobes. The most frequent species was Eubacterium lentum, followed by Clostridium perfringens. It could be suggested that nitric oxide synthase might produce a bacterial substrate increasing the growth of bacteria with a high pathogenic potential, creating conditions for chronic inflammation and infection in patients with excluded colon.

Adult↗

Association between myelodysplastic syndromes and inflammatory bowel diseases. Report of seven new cases and review of the literature.

We report seven patients with both myelodysplastic syndrome (MDS) and inflammatory bowel disease (IBD): Crohn's disease in six cases, ulcerative colitis in one case. We describe their characteristics, and those of 10 previously published similar cases are presented here. Median age at diagnosis of IBD (61 years) was high, as compared to the usual age at diagnosis of IBD. IBD was diagnosed first in nine cases, MDS first in one patient, and both diseases were diagnosed simultaneously in seven cases. Concerning IBD, there was a strong predominance of Crohn's disease (15/17 cases), with an unusually high frequency of colonic involvement (11/15 cases). MDS, in 12/17 cases, showed no excess of marrow blasts. Cytogenetic analysis was abnormal in five of the 13 evaluable cases. These observations suggest that the association between MDS and IBD may not be fortuitous in some cases, and that, in particular, patients with IBD and anemia of nonobvious origin should be evaluated for MDS. The pathogenesis of those associations, however, remains unclear.

Adult↗

TAP gene transporter polymorphism in inflammatory bowel diseases.

BACKGROUND: Many studies suggest the implication of genetic factors in inflammatory bowel diseases. Despite some associations with HLA genes, the lack of definite data may be due to ethnic variations, clinical heterogeneity, or the involvement of additional susceptibility genes beside or within the major histocompatibility complex (MHC), such as TAP genes. The aim of this study was to analyze in patients with ulcerative colitis (UC) or Crohn's disease (CD) the polymorphism of TAP genes that encode the proteins necessary for the transfer of antigenic peptides through the endoplasmic reticulum membrane. METHODS: One hundred and one UC and 148 CD patients were compared with 173 unrelated healthy controls. Dimorphisms within the TAP1 and TAP2 alleles were analyzed by sequence-specific oligonucleotide typing. RESULTS: No difference was found between patient groups and controls. However, when CD patients were classified on the basis of their responsiveness to steroid therapy, a significant decrease of TAP2 AA (*0101/*0101) genotype was found in CD patients who did not respond to steroid therapy (22.9% versus 43.7% in steroid responder group; Pc < 0.05; odds ratio = 2.6; 95% confidence limits (CL) = 1.2-5.9). These data appear independent of the distribution of HLA DRB1*01 or DRB1*03 alleles despite a significant linkage disequilibrium between these alleles and TAP2A. CONCLUSIONS: This result suggests, despite the absence of arguments favoring a genetic susceptibility to CD, that the TAP2 gene or other genes located on chromosome 6 may be involved in the genetic heterogeneity of CD.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Colonic xanthelasma due to glyceride accumulation associated with an adenoma.

The case is reported of a 66-year-old woman who presented with endoscopic and histological features of multiple lipid deposits in the mucosa of the sigmoid colon associated with an adenoma. Associated clinical features were abdominal pain and diarrhea. Colectomy led to the complete resolution of symptoms. Biochemical analysis disclosed the presence of glycerides in the mucosa. The pathogenesis of lipid deposits and the possible link with the formation of an adenoma is discussed.

Adenomatous Polyps↗

[Chronic pancreatitis: an extraintestinal manifestation of hemorrhagic rectocolitis?].

We reported here a case of unexplained chronic pancreatitis diagnosed 4 years before the onset of ulcerative colitis. The diagnosis of chronic pancreatitis was confirmed by recurrent pancreatitis and irregularities of the main pancreatic duct on retrograde pancreatography. None of the classical etiologies for chronic pancreatitis was found. Chronic pancreatitis associated with ulcerative colitis has already been reported in 5 cases. Our case reinforces the hypothesis of a non fortuitous association between both diseases.

Adult↗