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High-Level Serum Antibodies to Bacterial Antigens Are Associated with Antibiotic-Induced Clinical Remission in Crohn's Disease: A Pilot Study

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Abstract

In Crohn's disease, antibiotics are used with variable efficacy, suggesting that some patients are more likely to respond. The aim of this study was to determine whether Crohn's patients with predominant serum antibody reactivity toward bacterial antigens OmpC and/or I2 were more likely to achieve remission with antibiotics. Patients with ileal or ileal with right-sided colonic Crohn's disease were studied in a double-blind trial of budesonide alone or budesonide plus metronidazole and ciprofloxacin. In the budesonide plus metronidazole and ciprofloxacin group, patients with OmpC/I2 predominant profiles had the highest remission rate, whereas the group with no antibody predominant profiles had the lowest rate. In the budesonide group, patients with the OmpC/I2 predominant profile had the lowest remission rate, and the no-antibody group rate was higher. Although not statistically significant, these results support further testing to determine whether predominant serum reactivity to certain bacterial antigens may be a marker for efficacious use of antibiotics.

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REFERENCES

  1. Strober W, Fuss IJ, Blumberg RS: The immunology of mucosal models of inflammation. Annu Rev Immunol 20:495, 2002

    Google Scholar 

  2. De Winter H, Cheroutre H, Kronenberg M: Mucosal immunity and inflammation. II. The yin and yang of T cells in intestinal inflammation: Pathogenic and protective roles in a mouse colitis model. Am J Physiol 276:G1317, 1999

    Google Scholar 

  3. Pizarro TT, Arseneau KO, Bamias G, Cominelli F: Mouse models for the study of Crohn's disease. Trends Mol Med 9:218, 2003

    Google Scholar 

  4. Shanahan F: The host-microbe interface within the gut. Best Pract Res Clin Gastroenterol 16:915, 2002

    Google Scholar 

  5. McCarthy J, O'Mahony L, O'Callaghan L, Sheil B, Vaughan EE, Fitzsimons N, Fitzgibbon J, O'Sullivan GC, Kiely B, Collins JK, Shanahan F: Double blind, placebo controlled trial of two probiotic strains in interleukin 10 knockout mice and mechanistic link with cytokine balance. Gut 52:975, 2003

    Google Scholar 

  6. Cong Y, Brandwein SL, McCabe RP, Lazenby A, Birkenmeier EH, Sundberg JP, Elson CO: CD4+ T cells reactive to enteric bacterial antigens in spontaneously colitic C3H/HeJBir mice: Increased T helper cell type 1 response and ability to transfer disease. J Exp Med 187:855, 1998

    Google Scholar 

  7. Cong Y, Weaver CT, Lazenby A, and Elson CO: Bacterial-reactive T regulatory cells inhibit pathogenic immune responses to the enteric flora. J Immunol 169:6112, 2002

    Google Scholar 

  8. Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, Rennick DM, Sartor RB: Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun 66:5224, 1998

    Google Scholar 

  9. D'Haens GR, Geboes K, Peeters M, Baert F, Penninckx F, Rutgeerts P: Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology 114:262, 1998

    Google Scholar 

  10. Gupta P, AndrewH, Kirschner BS, Guandalini S: Is lactobacillusGG helpful in children with Crohn's disease? Results of a preliminary, open-label study. J Pediatr Gastroenterol Nutr 31:453, 2000

    Google Scholar 

  11. Guslandi M, Mezzi G, Sorghi M, Testoni PA: Saccharomyces boulardii in maintenance treatment of Crohn's disease. Dig Dis Sci 45:1462, 2000

    Google Scholar 

  12. Dunne C, O'Mahony L, Murphy L, Thornton G, Morrissey D, O'Halloran S, Feeney M, Flynn S, Fitzgerald G, Daly C, Kiely B, O'Sullivan GC, Shanahan F, Collins JK: In vitro selection criteria for probiotic bacteria of human origin: Correlation with in vivo findings. Am J Clin Nutr 73:386S, 2001

    Google Scholar 

  13. Shanahan F: Turbo probiotics for IBD. Gastroenterology 120:1297, 2001

    Google Scholar 

  14. Cohavy O, Bruckner D, Gordon LK, Misra R, Wei B, Eggena ME, Targan SR, Braun J: Colonic bacteria express an ulcerative colitis pANCA-related protein epitope. Infect Immun 68:1542, 2000

    Google Scholar 

  15. Eggena M, Cohavy O, Parseghian MH, Hamkalo BA, Clemens D, Targan SR, Gordon LK, Braun J: Identification of histone Hl as a cognate antigen of the ulcerative colitis-associated marker antibody pANCA. Autoimmun 14:83, 2000

    Google Scholar 

  16. Quinton JF, Sendid B, Reumaux D, Duthilleul P, Cortot A, Grandbastien B, Charrier G, Targan SR, Colombel JF, Poulain D: Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: Prevalence and diagnostic role. Gut 42:788, 1998

    Google Scholar 

  17. Prantera C, Zannoni F, Scribano ML, Berto E, Andreoli A, Kohn A, Luzi C: An antibiotic regimen for the treatment of active Crohn's disease: A randomized, controlled clinical trial of metronidazole plus ciprofloxacin. Am J Gastroenterol 91:328, 1996

    Google Scholar 

  18. Prantera C, Kohn A, Mangiarotti R, Andreoli A, Luzi C: Antimycobacterial therapy in Crohn's disease: Results of a controlled, double-blind trial with a multiple antibiotic regimen. Am J Gastroenterol 89:513, 1994

    Google Scholar 

  19. Prantera C, Kohn A, Zannoni F, Spimpolo N, Bonfa M: Metronidazole plus ciprofloxacin in the treatment of active, refractory Crohn's disease: Results of an open study. J Clin Gastroenterol 19:79, 1994

    Google Scholar 

  20. Greenbloom SL, Steinhart AH, Greenberg GR: Combination ciprofloxacin and metronidazole for active Crohn's disease. Can J Gastroenterol 12:53, 1998

    Google Scholar 

  21. Steinhart AH, Feagan BG, Wong CJ, Vandervoort M, Mikolainis S, Croitoru K, Seidman E, Leddin DJ, Bitton A, Drouin E, Cohen A, Greenberg GR: Combined budesonide and antibiotic therapy for active Crohn's disease: A randomized controlled trial. Gastroenterology 123:33, 2002

    Google Scholar 

  22. Hugor JP, Chamailard M, Zouali H, Lesage S, Cezard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G: Association of NOD2 leucine-rich repeat vaiants with susceptibility to Crohn's disease. Nature 411:599, 2001

    Google Scholar 

  23. Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Fernandez-Luna JL, Nunez G: Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J Biol Chem 278:5509, 2003

    Google Scholar 

  24. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nunez G, Cho JH: A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411:603, 2001

    Google Scholar 

  25. Peeters M, Joossens S, Vermeire S, Vlietinck R, Bossuyt X, Rutgeerts P: Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease. Am J Gastroenterol 96:730, 2001

    Google Scholar 

  26. Satsangi J, Landers CJ, Welsh KI, Koss K, Targan S, Jewell DP: The presence of anti-neutrophil antibodies reflects clinical and genetic heterogeneity within inflammatory bowel disease. Inflamm Bowel Dis 4:18, 1998

    Google Scholar 

  27. Ruemmele FM, Targan SR, Levy G, DubinskyM, Braun J, Seidman EG: Diagnostic accuracy of serological assays in pediatric inflammatory bowel disease. Gastroenterology 115:822, 1998

    Google Scholar 

  28. Tanabe T, Chamaillard M, Ogura Y, Zhu L, Qiu S, Masumoto J, Ghosh P, Moran A, Predergast MM, Tromp G, Williams CJ, Inohara N, Nunez G: 2004. Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition. EMBO J 23:1587, 2004

    Google Scholar 

  29. Sutton CL, Kim J, Yamane A, Dalwadi H, Wei B, Landers C, Targan SR, Braun J: Identification of a novel bacterial sequence associated with Crohn's disease. Gastroenterology 119:23, 2000

    Google Scholar 

  30. Landers CJ, Cohavy O, Misra R, Yang H, Lin YC, Braun J, Targan SR: Selected loss of tolerance evidenced by Crohn's diseaseassociated immune responses to auto-and microbial antigens. Gastroenterology 123:689, 2002

    Google Scholar 

  31. Sutton CL, Yang H, Li Z, Rotter JI, Targan SR, Braun J: Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in affected and unaffected relatives of patients with Crohn's disease. Gut 46:58, 2000

    Google Scholar 

  32. Saxon A, Shanahan F, Landers C, Ganz T, Targan S: A distinct subset of antineutrophil cytoplasmic antibodies is associated with inflammatory bowel disease. J Allergy Clin Immunol 86:202, 1990

    Google Scholar 

  33. Sutherland L, Singleton J, Sessions J, et al.: Double blind placebo controlled trial of metronidazole in Crohn's disease. Gut 32:1071, 1991

    Google Scholar 

  34. Taylor KD, Plevy SE, Yang H, Landers CJ, Barry MJ, Rotter JI, Targan SR: ANCA pattern and LTA haplotype relatioship to clinical responses to anti-TNF antibody treatment in Crohn's disease. Gastroenterology 120:1347, 2001

    Google Scholar 

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Authors and Affiliations

  1. Inflammatory Bowel Disease Center, Division of Gastroenterology, Cedars–Sinai Medical Center and UCLA School of Medicine, Los Angeles, California, USA

    William S. Mow, Carol J. Landers & Stephan R. Targan

  2. Division of Gastroenterology, Mount Sinai Hospital, Department of Medicine, University of Toronto, Toronto, Ontario

    A. Hillary Steinhart & Gordon R. Greenberg

  3. Robarts Clinical Trials Research Group, The John P. Robarts Research Institute, London, Ontario

    Brian G. Feagan & Ken Croitoru

  4. Gastroenterology Division, St. Justine Hospital, Montreal, Quebec, Canada

    Ernest Seidman

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  1. William S. Mow
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  2. Carol J. Landers
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  3. A. Hillary Steinhart
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  4. Brian G. Feagan
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  7. Gordon R. Greenberg
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  8. Stephan R. Targan
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Mow, W.S., Landers, C.J., Steinhart, A.H. et al. High-Level Serum Antibodies to Bacterial Antigens Are Associated with Antibiotic-Induced Clinical Remission in Crohn's Disease: A Pilot Study. Dig Dis Sci 49, 1280–1286 (2004). https://doi.org/10.1023/B:DDAS.0000037824.66186.e2

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  • DOI: https://doi.org/10.1023/B:DDAS.0000037824.66186.e2

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