Selected Bacterial Antibodies in Crohn's Disease and Ulcerative Colitis

Auer, I. O.; Röder, A; Wensinck, F.; Merwe, J. P. van de; Schmidt, Hartmut

doi:10.3109/00365528309181586

Cited by 63 publications

(20 citation statements)

References 15 publications

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“…Members of the family Pseudomonadaceae are rare components of fecal bacteria of the colon, usually below the limits of culture detection (16,48). There are reports associating fecal Pseudomonadaceae with CD (17,18), but the findings are inconsistent (3,20,33). Similarly, the present study did not detect fecal P. fluorescens in CD patients, but the limits of detection were 10,000 CFU or 2,000 gene copies per g of stool, respectively, for culture or PCR assay.…”

Section: Discussionmentioning

confidence: 99%

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Pseudomonas fluorescens Encodes the Crohn's Disease-Associated I2 Sequence and T-Cell Superantigen

Wei¹,

Huang

Dalwadi³

et al. 2002

Infect Immun

122

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Commensal bacteria have emerged as an important disease factor in human Crohn's disease (CD) and murine inflammatory bowel disease (IBD) models. We recently isolated I2, a novel gene segment of microbial origin that is associated with human CD and that encodes a T-cell superantigen. To identify the I2 microorganism, BLAST analysis was used to identify a microbial homologue, PA2885, a novel open reading frame (ORF) in the Pseudomonas aeruginosa genome. PCR and Southern analysis identified Pseudomonas fluorescens as the originating species of I2, with homologues detectable in 3 of 13 other Pseudomonas species. Genomic cloning disclosed a locus containing the full-length I2 gene (pfiT) and three other orthologous genes, including a homologue of the pbrA/pvdS iron response gene. CD4؉ T-cell responses to recombinant proteins were potent for I2 and pfiT, but modest for PA2885. pfiT has several features of a virulence factor: association with an iron-response locus, restricted species distribution, and T-cell superantigen bioactivity. These findings suggest roles for pfiT and P. fluorescens in the pathogenesis of Crohn's disease.Human inflammatory bowel disease (IBD) represents a set of a chronic, relapsing, and remitting intestinal inflammatory disorders involving T-cell-mediated mucosal and mural destruction, with polygenic disease susceptibility (4, 13, 38). Although the etiology of these diseases remains uncertain, several lines of evidence implicate commensal bacteria as an important pathogenic element in clinical disease, particularly in Crohn's disease (CD). Patients with CD are sensitive to alteration of fecal flow, and some investigators have reported evidence of a clinical responsiveness to antibiotic therapy (21,24,34). In both pharmacologic and genetic animal models of IBD, development of disease is strictly dependent on the presence of enteric microflora (19,29,(35)(36)(37)40).The identity of colitigenic bacterial species remains uncertain. In humans, a variety of bacterial and viral species have been implicated in CD, mainly on the basis of seroreactivity (3,5,8,28,44). However, CD patients typically express elevated levels of antibodies to many bacterial proteins, perhaps due to mucosal disruption and local immunologic challenge by diverse intestinal microflora. Mycobacterium has received attention as a candidate human pathogen, based on serologic evidence, but the presence of mycobacterial DNA in lesions is controversial (9,12,31,32,43,47). Bacteroides vulgatus and Helicobacter hepaticus have been evaluated with various rodent IBD models, but other intestinal commensal organisms yet undefined are likely to account for the major colitigenic species (14,25,35,36).Our laboratory recently introduced subtractive cloning as a fresh approach to identify candidate organisms in human CD (10, 45). A novel microbial gene, I2, was isolated from lesional versus adjacent uninvolved colon tissues of a patient with CD. In a population-based study (45), the I2 gene was selectively detected in lesional CD colonic tissue,...

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Section: Discussionmentioning

confidence: 99%

“…In humans, a variety of bacterial and viral species have been implicated in CD, mainly on the basis of seroreactivity (3,5,8,28,44). However, CD patients typically express elevated levels of antibodies to many bacterial proteins, perhaps due to mucosal disruption and local immunologic challenge by diverse intestinal microflora.…”

mentioning

confidence: 99%

Pseudomonas fluorescens Encodes the Crohn's Disease-Associated I2 Sequence and T-Cell Superantigen

Wei¹,

Huang

Dalwadi³

et al. 2002

Infect Immun

122

View full text Add to dashboard Cite

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“…Monoassociation studies have implicated Bacteroides vulgatus as a pathogenic factor in a rat transgenic model of colitis (27). CD is distinguished not only by antibody immunoreactivity to several colonic bacterial taxa (1,3,50), but also by a striking expansion of T cells reactive to autologous colonic bacteria, including B. thetaiotaomicron (14). Gut-associated T lymphocytes are remarkably anergic to colonic bacterial antigens.…”

Section: Discussionmentioning

confidence: 99%

Molecular Cloning of aBacteroides caccaeTonB-Linked Outer Membrane Protein Identified by an Inflammatory Bowel Disease Marker Antibody

Wei¹,

Dalwadi²,

Gordon

et al. 2001

Infect Immun

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Commensal enteric bacteria are a required pathogenic factor in inflammatory bowel disease (IBD), but the identity of the pertinent bacterial species is unresolved. Using an IBD-associated pANCA monoclonal antibody, a 100-kDa protein was recently characterized from an IBD clinical isolate of Bacteroides caccae (p2Lc3). In this study, consensus oligonucleotides were designed from 100-kDa peptides and used to identify a single-copy gene from the p2Lc3 genome. Sequence analysis of the genomic clone revealed a 2,844-bp (948 amino acid) open reading frame encoding features typical of the TonB-linked outer membrane protein family. This gene, termed ompW, was detected by Southern analysis only in B. caccae and was absent in other species of Bacteroides and gram-negative coliforms. The closest homologues of OmpW included the outer membrane proteins SusC of Bacteroides thetaiotaomicron and RagA of Porphyromonas gingivalis. Recombinant OmpW protein was immunoreactive with the monoclonal antibody, and serum anti-OmpW immunoglobulin A levels were elevated in a Crohn's disease patient subset. These findings suggest that OmpW may be a target of the IBD-associated immune response and reveal its structural relationship to a bacterial virulence factor of P. gingivalis and periodontal disease.Human inflammatory bowel disease (IBD) represents a set of a chronic, relapsing, and remitting intestinal inflammatory disorders involving T-cell-mediated mucosal and mural destruction and polygenic familial susceptibility (34,35). Several spontaneous and transgenic mouse strains have been established with susceptibility for chronic colitis similar to human IBD (4,5,18,20,26,32). In all evaluated models, normal resident enteric bacteria were found to be required for disease pathogenesis (13,27,40). Similarly, in human IBD several lines of evidence implicate enteric bacteria as a pathogenic factor in clinical disease, particularly in Crohn's disease (CD) (3,33,48).Immunologic studies have demonstrated that antibody and T-cell reactivity to commensal enteric bacteria is a distinguishing feature of colitic mouse strains (6, 10). However, the bacterial species and antigens recognized by colitigenic T cells have not yet been defined. Moreover, monoassociation studies have not yet revealed pathogenic bacterial species for colitisprone mouse strains (27). A systematic approach to this issue is hampered by the limited understanding of gastrointestinal microflora ecosystem. In addition, immune recognition of this commensal microflora in normal individuals is attenuated or undetectable. Accordingly, it has been difficult to highlight bacterial species or antigens for evaluation in IBD pathogenesis.Marker antibodies have been used successfully to identify disease-relevant antigenic targets in several immune-mediated diseases (38,45). In IBD, approximately 60 to 70% of ulcerative colitis (UC) patients and 25% of CD patients have elevated levels of pANCA, an antineutrophil cytoplasmic antibody with distinctive morphological and antigenic fine specificity ...

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“…Nevertheless, the belief persists, supported by a body of evidence (8,10,34), some of it questioned (2,3,26), that mycobacteria do play a role in the pathogenesis of Crohn's disease. Regardless of the disease import, we advocate the principle that a study of the variable antigenic facade of Mycobacterium spp.…”

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confidence: 96%

Location of acyl groups of trehalose-containing lipooligosaccharides of mycobacteria

et al. 1987

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A variant of a Mycobacterium sp. originating in a patient with Crohn's disease, but not necessarily implicated in the disease, provided a simple version of a newer class of species-specific surface glycolipids, the trehalose-containing lipooligosaccharides. A combination of high-resolution 1H nuclear magnetic resonance, methylation, ethylation, and absolute configurational analysis established the structure of the oligosaccharide unit as beta-D-Glcp(1----3)-alpha-L-Rhap(1----3)-alpha-D-Glcp(1----1)-alph a-D-Glcp (where Glc is glucose, Rha is rhamnose, and p is pyranosyl), and gas chromatography-electron impact mass spectrometry allowed identification of the fatty acyl esters as primarily 2,4-dimethyltetradecanoate. The relative simplicity of the glycolipid combined with the application of a mild methylation procedure and californium-252 plasma desorption mass spectrometry allowed recognition of three such acyl residues on the 3-, 4-, and 6-hydroxyl positions of the terminal glucosyl residue of the trehalose unit. Thus, the glycolipid is decidedly amphipathic yet is clearly not membranous. This observation leads to speculation about the role of these novel lipooligosaccharides in contributing to the outer segment of the hydrophobic barrier of the cell wall of certain mycobacteria.

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Selected Bacterial Antibodies in Crohn's Disease and Ulcerative Colitis

Cited by 63 publications

References 15 publications

Pseudomonas fluorescens Encodes the Crohn's Disease-Associated I2 Sequence and T-Cell Superantigen

Pseudomonas fluorescens Encodes the Crohn's Disease-Associated I2 Sequence and T-Cell Superantigen

Molecular Cloning of aBacteroides caccaeTonB-Linked Outer Membrane Protein Identified by an Inflammatory Bowel Disease Marker Antibody

Location of acyl groups of trehalose-containing lipooligosaccharides of mycobacteria

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