Identification of a novel bacterial sequence associated with Crohn's disease

Background & Aims: Enteric microorganisms are implicated in the pathogenesi s 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 mono nuclear cells of lesional mucosa vs. adjacent uninvolved mucosa, Methods: T wo RDA-derived microbial sequences were isolated (11 and 12) and identified as novel homologues of the ptxR and tetR bacterial transcription-factor fa milies. Results: Quantitative competitive polymerase chain reaction of para ffin-embedded intestinal specimens from 212 patients showed that 12 DNA was present in many CD colonic lesions (43%), but was infrequent in other colo nic specimens (9% of ulcerative colitis lesions and 5% of non-inflammatory bowel disease diseases; P < 0,0001). 12 was prevalent in ileal specimens, r egardless of disease status (43%-54%). Enzyme-linked immunosorbent assay an alysis of 150 individuals with an 12 glutathione-S-transferase fusion prote in showed frequent immunoglobulin A seroreactivity in CD (54% of patients), but infrequent seroreactivity in patients with ulcerative colitis, other i nflammatory enteric diseases, or normals (10%, 19%, and 4%, respectively; P < 0.001 to 0.00001), Conclusions: These findings relate CD to a novel lesi on-localized and immunologically associated bacterial sequence, suggesting that the microorganism expressing the 12 gene product may be related to CD pathogenesis.