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

被引:170
作者
Sutton, CL
Kim, J
Yamane, A
Dalwadi, H
Wei, B
Landers, C
Targan, SR
Braun, J
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA
[3] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA
[4] Cedars Sinai Med Ctr, Inflammatory Bowel Dis Res Ctr, Los Angeles, CA 90048 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1053/gast.2000.8519
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: 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 (11 and 12) 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 12 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). 12 was prevalent in ileal specimens, regardless of disease status (43%-54%). Enzyme-linked immunosorbent assay analysis of 150 individuals with an 12 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 12 gene product may be related to CD pathogenesis.
引用
收藏
页码:23 / 31
页数:9
相关论文
共 46 条
[21]   SEQUENCE AND CHARACTERISTICS OF IS900, AN INSERTION ELEMENT IDENTIFIED IN A HUMAN CROHNS-DISEASE ISOLATE OF MYCOBACTERIUM-PARATUBERCULOSIS [J].
GREEN, EP ;
TIZARD, MLV ;
MOSS, MT ;
THOMPSON, J ;
WINTERBOURNE, DJ ;
MCFADDEN, JJ ;
HERMONTAYLOR, J .
NUCLEIC ACIDS RESEARCH, 1989, 17 (22) :9063-9073
[22]   EUKARYOTIC PROTEINS EXPRESSED IN ESCHERICHIA-COLI - AN IMPROVED THROMBIN CLEAVAGE AND PURIFICATION PROCEDURE OF FUSION PROTEINS WITH GLUTATHIONE-S-TRANSFERASE [J].
GUAN, KL ;
DIXON, JE .
ANALYTICAL BIOCHEMISTRY, 1991, 192 (02) :262-267
[23]   Two-year-outcomes analysis of Crohn's disease treated with rifabutin and macrolide antibiotics [J].
Gui, GPH ;
Thomas, PRS ;
Tizard, MLV ;
Lake, J ;
Sanderson, JD ;
HermonTaylor, J .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1997, 39 (03) :393-400
[24]   Mapping of a susceptibility locus for Crohn's disease on chromosome 16 [J].
Hugot, JP ;
LaurentPuig, P ;
GowerRousseau, C ;
Olson, JM ;
Lee, JC ;
Beaugerie, L ;
Naom, I ;
Dupas, JL ;
VanGossum, A ;
Orholm, M ;
BonaitiPellie, C ;
Weissenbach, J ;
Mathew, CG ;
LennardJones, JE ;
Cortot, A ;
Colombel, JF ;
Thomas, G .
NATURE, 1996, 379 (6568) :821-823
[25]   The role of the fecal stream in Crohn's disease: An historical and analytical review [J].
Janowitz, HD ;
Croen, EC ;
Sachar, DB .
INFLAMMATORY BOWEL DISEASES, 1998, 4 (01) :29-39
[26]  
Kam LY, 1999, GASTROENTEROLOGY, V116, pA744
[27]  
Khoo UY, 1997, J IMMUNOL, V158, P3626
[28]   CLONING THE DIFFERENCES BETWEEN 2 COMPLEX GENOMES [J].
LISITSYN, N ;
LISITSYN, N ;
WIGLER, M .
SCIENCE, 1993, 259 (5097) :946-951
[29]   Crohn's disease in Olmsted County, Minnesota, 1940-1993: Incidence, prevalence, and survival [J].
Loftus, EV ;
Silverstein, MD ;
Sandborn, WJ ;
Tremaine, WJ ;
Harmsen, WS ;
Zinsmeister, AR .
GASTROENTEROLOGY, 1998, 114 (06) :1161-1168
[30]   ANTIBODY TO SACCHAROMYCES CEREVISIAE (BAKERS-YEAST) IN CROHNS-DISEASE [J].
MAIN, J ;
MCKENZIE, H ;
YEAMAN, GR ;
KERR, MA ;
ROBSON, D ;
PENNINGTON, CR ;
PARRATT, D .
BRITISH MEDICAL JOURNAL, 1988, 297 (6656) :1105-1106