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Presence of hsp65 in bacterial extracts (OM-89): A possible mediator of orally-induced tolerance?

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Abstract

Heat shock proteins (HSP) have been implicated in rodent models of autoimmunity, particularly arthritis, and there is suggestive though inconclusive evidence that they may also play a role in human autoimmune disease. The simplest hypothesis is based on molecular mimicry due to the amino-acid sequence homology between mammalian and microbial HSP. Recently OM-89, an extract of several strains ofEscherichia coli, has shown some efficacy in the treatment of rheumatoid arthritis (RA) when taken orally. Using species-specific antibodies, we show here that OM-89 contains the 65 kDa HSP (hsp65), while hsp65 was not detected in another bacterial extract containing other microorganisms, includingStaphylococcus aureus (OM-85). We suggest that if the human homologue of hsp65 is a relevant target antigen in the human disease, the efficacy of the preparation could be due to induction of oral tolerance or to switching the Th1 response towards Th2. Alternatively, even if the human hsp65 is not a target molecule in RA joints, OM-89 may evoke bystander suppression of joint inflammation via induction of TGFβ-secreting effector cells. These hypotheses should be tested in further studies.

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References

  1. Lindquist, S., and Craig, E., A. Rev. Genet.22 (1988) 631.

    Article  CAS  Google Scholar 

  2. Becker, J., and Craig, E. A., Eur. J. Biochem.219 (1994) 11.

    Article  CAS  PubMed  Google Scholar 

  3. Kaufmann, S. H. E., Immun. Today11 (1992) 129.

    Article  Google Scholar 

  4. De Nagel, D. C., and Pierce, S. K., Immun. Today13 (1992) 86.

    Article  Google Scholar 

  5. Mariéthoz, E., Tacchini-Cottier, F., Jacquier-Sarlin, M. R., Sinclair, F., and Polla, B. S., Int. Immun.6 (1994) 925.

    Article  PubMed  Google Scholar 

  6. Srivastava, P. K., Udono, H., Blachere, N. E., and Li, Z., Immunogenetics39 (1994) 93.

    Article  CAS  PubMed  Google Scholar 

  7. van Eden, W., Thole, J. E. R., van der Zee, R., Noordzij, A., van-Embden, J. D. A., Hensen, E. J., and Cohen, I. R., Nature331 (1988) 171.

    Article  PubMed  Google Scholar 

  8. Anderton, S. M., van der Zee, R., Noordzij, A., and van Eden, W., J. Immun.152 (1994) 3656.

    Article  CAS  PubMed  Google Scholar 

  9. Thompson, S. J., Hitsumoto, Y., Ghoraishian, M., van der Zee, R., and Elson, C. J., Autoimmunity11 (1991) 89.

    Article  CAS  PubMed  Google Scholar 

  10. van den Broek, M. F., van Bruggen, M. C. J., Hogervorst, E. J. M., van Eden, W., van der Zee, R., and van den Berg, W. B., J. expl Med.170 (1989) 449.

    Article  Google Scholar 

  11. Lamb, J. R., Bal, V., Mendez-Samperio, P., Mehlert, A., So, A., Rothbard, J., Jindal, S., Young, R. A., and Young, D. B., Int. Immun.1 (1989) 191.

    Article  CAS  PubMed  Google Scholar 

  12. Young, D. B., Semin. cell. Biol.1 (1990) 27.

    CAS  PubMed  Google Scholar 

  13. Young, R. A., Rev. Immun.8 (1990) 401.

    Article  CAS  Google Scholar 

  14. Munk, M. E., Schoel, B., Modrow, S., Karr, R. W., Young, R. A., and Kaufman, S. H. E., J. Immun.143 (1989) 2844.

    Article  CAS  PubMed  Google Scholar 

  15. Boog, C. J. P., de Graeff-Meeder, E. R., Lucassen, M. A., van der Zee, R., Voorhorst-Ogink, M. M., van Kooten, P. J. S., Geuze, H. J., and van Eden, W., J. expl Med.175 (1992) 1805.

    Article  CAS  Google Scholar 

  16. Sharif, M., Worral, J., Singh, B., Gupta, R. S., Lydyard, P. M., Lambert, C., McCulloch, J., and Rook, G. A. W., Arthritis Rheum.35 (1992) 1427.

    Article  CAS  PubMed  Google Scholar 

  17. Bahr, G. M., Rook, G. A. W., Al Saffar, M., van Embden, J., Stanford, J. L., and Behbehani, K., Clin. expl Immun.74 (1988) 211.

    CAS  Google Scholar 

  18. Tsoulfa, G., Rook, G. A. W., Bahr, G., Sattar, M. A., Young, D. B., Mehlert, A., van Embden, J. D. A., Hay, F., Isenberg, D., and Lydyard, P. M., Scand. J. Immun.30 (1988) 519.

    Article  Google Scholar 

  19. Gaston, J. S., Life, P. F., van der Zee, R., Jenner, P. J., Colston, M. J., Tonks, S., and Bacon, P. A., Int. Immun.3 (1991) 965.

    Article  CAS  PubMed  Google Scholar 

  20. Res, P. C., Schaar, C. G., Breedveld, F. C., van Eden, W., van Embden, J. D., Cohen, I. R., and de Vries, R. R., Lancetii (1988) 478.

    Article  Google Scholar 

  21. Bessler, W. G., Kleine, B., Martinez Alonso, C., Biesert, L., Strecker, M., Wiesmüller, K.-H., Metzger, J., and Jung, G., Lung168 (Suppl.) (1990) 707.

    Article  CAS  PubMed  Google Scholar 

  22. Lusuardi, M., Capelli, A., Carli, S., Spada, E. L., Spinazzi, A., and Donner, C. F., Chest103 (1993) 1783.

    Article  CAS  PubMed  Google Scholar 

  23. Mauel, J., Pham, T. V., Kreis, B., and Bauer, J., Int. J. Immunopharmac.11 (1989) 637.

    Article  CAS  Google Scholar 

  24. Baladi, S., Kantengwa, S., Donati, Y. R. A., and Polla, B. S., Mediators Inflam.3 (1994) 143.

    Article  CAS  Google Scholar 

  25. Vischer, T. L., Ann. Rheum. Dis.47 (1988) 582.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Vischer, T. L., Clin. Rheum.9 (1990) 356.

    Article  CAS  Google Scholar 

  27. Polla, B. S., Healy, A., Amento, E., and Krane, S. M., J. clin. Invest.77 (1986) 1332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rosenberg, H. F., Ackerman, S. J., and Tenen, D. G., J. biol. Chem.268 (1993) 4499.

    Article  CAS  PubMed  Google Scholar 

  29. Laemmli, U. K., Nature227 (1970) 680–685.

    Article  CAS  PubMed  Google Scholar 

  30. Barrios, C., Tougne, C., Polla, B. S., Lambert, P.-H., and Del Giudice, G., Clin. expl. Immun.98 (1994) 224.

    Article  CAS  Google Scholar 

  31. Müller-Fassbender, H. R., Br. J. Rheum.32 (1993) 746.

    Article  Google Scholar 

  32. van Eden, W., Immun. Rev.121 (1991) 5.

    Article  PubMed  Google Scholar 

  33. Buchan, G., Barret, K., Fujita, T., Taniguchi, T., Maini, R., and Feldmann, M., Clin. expl Immun.71 (1988) 295.

    CAS  Google Scholar 

  34. Firestein, G. S., and Zvaifler, N. J., Arthritis Rheum.33 (1990) 768.

    Article  CAS  PubMed  Google Scholar 

  35. Weinblatt, M. E., Coblyn, J. S., Fraser, P. A., Anderson, R. J., Tretham, D. E., and Austen, K. F., Arthritis Rheum.29 (1986) S79.

    Google Scholar 

  36. Chen, Y., Kuchroo, V. K., Inobe, J.-I., Hafler, D. A., and Weiner, H. W., Science265 (1994) 1237.

    Article  CAS  PubMed  Google Scholar 

  37. Khoury, S. J., Hancock, W. W., and Weiner, H. L., J. expl Med.176 (1992) 1355.

    Article  CAS  Google Scholar 

  38. Thompson, S. J., Thompson, H. S., Harper, N., Day, M. J., Coad, A. J., Elson, C. J., and Staines, N. A., Immunology79 (1993) 152.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhang, Z. Y., Lee, C. S., Lider, O., and Weiner, H. L., J. Immun.145 (1990) 2489.

    Article  CAS  PubMed  Google Scholar 

  40. Trentham, D. E., Dynesius-Trentham, R. A., Orav, E. J., Combitchi, D., Lorenzo, C., Sewell, K. L., Hafler, D. A., and Weiner, H. L., Science261 (1993) 1727.

    Article  CAS  PubMed  Google Scholar 

  41. Twisk, A. J. T., Jeurissen, S. H. M., Sminia, T., and Kraal, G., J. Immun. Immunopharmac.9 (1989) 68.

    Google Scholar 

  42. Farine, J. C., and Farre, A. J., Int. J. Immunopath. Pharm.1 (1988) 39.

    Google Scholar 

  43. Kohashi, O., Kohashi, Y., Takahashi, T., Ozawa, A., and Shigematsu, N., Arthritis Rhenum.29 (1986) 547–553.

    Article  CAS  Google Scholar 

  44. Feige, U., and Cohen, I. R., Springer Semin. Immunopath.13 (1991) 99.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Allergy Unit, University Hospital, CH-1211, Geneva 14, Switzerland

    B. S. Polla, S. Baladi & K. Fuller

  2. Laboratoire de Physiologie Respiratoire, UFR Cochin Port-Roya, 24 rue du Faubourg Saint Jacques, F-75014, Paris, France

    B. S. Polla & S. Baladi

  3. Department of Medical Microbiology, University College and Middlesex School of Medicine, W1P 7PN, London, England, UK

    G. Rook

Authors
  1. B. S. Polla
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  2. S. Baladi
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  3. K. Fuller
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  4. G. Rook
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Polla, B.S., Baladi, S., Fuller, K. et al. Presence of hsp65 in bacterial extracts (OM-89): A possible mediator of orally-induced tolerance?. Experientia 51, 775–779 (1995). https://doi.org/10.1007/BF01922429

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  • DOI: https://doi.org/10.1007/BF01922429

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