Identification of a novel bacterial sequence associated with Crohn's disease.
OBJECTIVE
Enteric microorganisms are implicated in the pathogenesis of Crohn's disease (CD), but no clear bacterial or viral species has been identified. In this study, representational difference analysis (RDA) was used to isolate DNA segments preferentially abundant in lamina propria mononuclear cells of lesional mucosa vs. adjacent uninvolved mucosa.


METHODS
Two RDA-derived microbial sequences were isolated (I1 and I2) and identified as novel homologues of the ptxR and tetR bacterial transcription-factor families.


RESULTS
Quantitative competitive polymerase chain reaction of paraffin-embedded intestinal specimens from 212 patients showed that I2 DNA was present in many CD colonic lesions (43%), but was infrequent in other colonic specimens (9% of ulcerative colitis lesions and 5% of non-inflammatory bowel disease diseases; P<0.0001). I2 was prevalent in ileal specimens, regardless of disease status (43%-54%). Enzyme-linked immunosorbent assay analysis of 150 individuals with an I2 glutathione-S-transferase fusion protein showed frequent immunoglobulin A seroreactivity in CD (54% of patients), but infrequent seroreactivity in patients with ulcerative colitis, other inflammatory enteric diseases, or normals (10%, 19%, and 4%, respectively; P<0.001 to 0.00001).


CONCLUSIONS
These findings relate CD to a novel lesion-localized and immunologically associated bacterial sequence, suggesting that the microorganism expressing the I2 gene product may be related to CD pathogenesis.
Sutton
C L
CL
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California, USA.
Kim
J
J
Yamane
A
A
Dalwadi
H
H
Wei
B
B
Landers
C
C
Targan
S R
SR
Braun
J
J
D000595:Amino Acid Sequence / Q000235:genetics; D001419:Bacteria / Q000302:isolation & purification; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005787:Gene Frequency; D005798:Genes, Bacterial; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008969:Molecular Sequence Data
D001426:Bacterial Proteins