Abstract
Many investigators have tried to prove a relationship between Crohn's disease andMycobacteria. Recent evidence suggests that some autoimmune diseases may be initiated through “molecular mimicry” between mycobacterial stress protein antigens and their human homologs. We investigated whether antibody to stress proteins was more frequent in patients with Crohn's disease than controls. We used ATP binding to separate stress proteins (heat-shock-induced,de novo-synthesized, and constitutively expressed ATP-binding proteins) from crude extracts obtained fromMycobacteria and from an SV40-transformed human epithelial cell line that expresses a heat-shock protein, hsp73, as a complex with SV40 T antigen. We used immunoblots to compare sera from 34 patients with Crohn's disease, 14 with ulcerative colitis, and 14 with duodenal or gastric ulcers (noninflammatory bowel disease control patients). We found no statistically significant pattern or frequency of antibodies against single proteins or a combination of mycobacterial or human stress proteins. These observations do not support the hypothesis that a humoral immune response to stress proteins ofMycobacteria is important in the pathogenesis of Crohn's disease.
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Chiodini RJ, Van Kruiningen HJ, Thayer WR, Merkal RS, Coutu A.: Possible role ofMycobacteria in inflammatory bowel disease. I. An unclassifiedMycobacterium species isolated from patients with Crohn's disease. Dig Dis Sci 29:1073–1078, 1984
Chiodini RJ, Van Kruiningen HJ, Merkal RS, Thayer WR, Coutu JA: Characteristics of an unclassifiedMycobacterium species isolated from patients with Crohn's disease. J Clin Microbiol 20:966–971, 1984
Yoshimura HH, Graham DY, Estes MK, Merkal RS: Investigation of association ofMycobacteria with IBD by nucleic acid hybridization. J Clin Microbiol 25:45–51, 1987
Morganroth J, Watson DW: Sensitivity to atypical mycobacterial antigens in patients with Crohn's disease. Dig Dis Sci 15:653–657, 1970
Grange JM, Gibson J, Nassau E: Enzyme-linked immunosorbent assay (ELISA): A study of antibodies toMycobacterium tuberculosis in the IgG, IgA, and IgM classes in tuberculosis, sarcoidosis, and Crohn's disease. Tubercle 61:145–152, 1980
Thayer WR, Coutu JA, Chiodini RJ, Van Kruiningen HJ, Merkal RS: Possible role ofMycobacteria in inflammatory bowel disease. Mycobacterial antibodies in Crohn's disease. Dig Dis Sci 29:1080–1085, 1984
Cho S, Brennan PJ, Yoshimura HH, Korelitz BI, Graham DY: Mycobacterial aetiology of Crohn's disease: Serologic study using common mycobacterial antigens and a species-specific glycolipid antigen fromMycobacterium paratuberculosis. Gut 27:1353–1356, 1986
Kobayashi K, Brown WR, Brennan PJ, Blaser MJ: Serum antibodies to mycobacterial antigens in active Crohn's disease. Gastroenterology 94:1404–1411, 1988
Young D, Lathigra R, Hendrix R, Sweetser D, Young RA: Stress proteins are immune targets in leprosy and tuberculosis. Proc Natl Acad Sci USA 85:4267–4270, 1988
Garsia RJ, Hellqvist L, Booth RJ, Radfork AJ, Britton WJ, Astbury L Trent RJ, Basten A: Homology of the 70kilodalton antigens fromMycobacterium leprae andMycobacterium bovis with theMycobacterium tuberculosis 71-kilodalton antigen and with the conserved heat shock protein 70 of eukaryotes. Infect Immun 57:204–212, 1989
Shinnick TM, Vodkin MH, Williams JC: TheMycobacterium tuberculosis 65-kilodalton antigen is a heat shock protein which corresponds to common antigen and to theEscherichia coli GroEL protein. Infect Immun 56:446–451, 1988
Welch WJ, Mizzen LA, Arrigo AP: Structure and function of mammalian stress proteins.In Stress Induced Proteins. Alan R. Liss, New York, 1989, pp 187–202
Pelham HRB: Speculations on the function of the major heat shock and glucose regulated proteins. Cell 46:959–961, 1986
VanEden W, Thole JER, Van der Zee R, Noordizij A, VanEmbden JDA, Hensen EJ, Cohen IR: Cloning of the mycobacterial epitope recognized by T-lymphocytes in adjuvant arthritis. Nature 331:171–173, 1988
Rook G, Lydyard P, Stanford J: Mycobacteria and rheumatoid arthritis. Arthritis Rheum 33:431–435, 1990
Shoenfeld Y, Isenberg DA:Mycobacteria and autoimmunity. Immun Today 9:178–182, 1988
Hill Gaston JS, Life PF, Jenner PJ, Colston MJ, Bacon PA: Recognition of aMycobacteria-specific epitope in the 65-kD heat-shock protein by synovial fluid-derived T cell clones. J Exp Med 171:831–841, 1990
Koga T, Wand-Wurttenberger A, Debruyn J, Munk ME, Schoel B, Kaufmann SHE: T cells against a bacterial heat shock protein recognize stressed macrophages. Science 245:1112–1115, 1989
Sawai ET, Butel JS: Association of cellular heat shoch protein with simian virus 40 large T antigen in transformed cells. J Virol 63:3961–3973, 1989
Welch WJ, Feramisco JR: Rapid purification of mammalian 70,000 dalton stress proteins: Affinity of the proteins for nucleotide. Mol Cell Biol 5:1229–1237, 1985
Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 221:680, 1970
Slagle BL, Lanford RE, Medina D, Butel JS: Expression of mammary tumor virus proteins in preneoplastic outgrowth lines and mammary tumors of BALB/CV mice. Cancer Res 44:2155–2162, 1984
Johnson DA, Gautsch JW, Sportsman JR, Elder JH: Improved techniques utilizing nonfat dry milk for analysis of proteins and nucleic acids transferred to nitrocellulose. Gene Anal Techn 1:3–8, 1984
Britton WJ, Hellqvist L, Garsia RJ, Basten A: Antigens ofMycobacterium leprae identified by immunoprecipitation with sera from leprosy and tuberculosis patients. Clin Exp Immunol 71:394–398, 1988
Young DB, Mehlert A, Bal V, Mendez-Samperio P, Ivanyi J, Lamb JR: Stress proteins and the immune response toMycobacteria-antigens as virulence factors? Antonie van Leeuwenhoek J Microbiol 54:431–439, 1988
Jindal S, Dudani AK, Singh B, Harley CB, Gupta RS: Primary structure of a human mitochondrial protein homologous to the bacterial and plant chaperonins and to the 65-kilodalton mycobacterial antigen. Mol Cell Biol 9:2279–2283, 1989
De Bruyn J, Bosmans R, Nyabenda J, Van Vooren JP: Effect of zinc deficiency on the appearance of two immunodominant protein antigens (32 K and 65 K) in culture filtrates ofMycobacteria. J Gen Microbiol 135:79–84, 1989
Borremans M, DeWit L, Volckaert G, et al.: Cloning, sequence determination, and expression of a 32-kilodalton protein gene ofMycobacterium tuberculosis. Infect Immun 57(10):3123–3130, 1989
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Markesich, D.C., Sawai, E.T., Butel, J.S. et al. Investigations on etiology of Crohn's disease. Digest Dis Sci 36, 454–460 (1991). https://doi.org/10.1007/BF01298874
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DOI: https://doi.org/10.1007/BF01298874