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Autoimmune mechanisms as the basis for human peripartum cardiomyopathy

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Abstract

The etiology and mechanisms of pathogenesis of human peripartum cardiomyopathy (PPCM) remain unknown. The incidence and prevalence of this disease is rare in some parts of the world and more common in others. The purpose of this review is to summarize our current knowledge of the factors that have been entertained which may contribute to the pathogenesis of PPCM with special emphasis on more recent data from our laboratory that provide support to the view that this disease is an autoimmune disease with multiple contributing factors and effector mechanisms. This is supported by the fact that sera from PPCM patients contain high titers of autoantibodies against normal human cardiac tissue proteins of 37, 33, and 25 kD that was not present in the sera of patients with idiopathic cardiomyopathy (IDCM), indicating for the first time that PPCM is distinct from IDCM. In addition to the autoantibodies, the PBMC's from PPCM patients demonstrate a heightened level of fetal microchimerism, an abnormal cytokine profile, decreased levels of CD4+ CD25lo regulatory T cells, and a significant reduction in the plasma levels of progesterone, estradiol and relaxin in PPCM patients as compared with other normal pregnant non-PPCM patients. A potential role for reduced plasma levels of selenium in the pathogenesis of select PPCM patients was also noted. These findings for the first time suggest that such abnormalities may in concert lead to the initiation and perpetuation of an autoimmune process, which leads to cardiac failure and disease. Identification of the precise nature of the cardiac tissue autoantigens (currently in progress) will pave the way for the delineation of mechanism of this autoimmune disease. A working model for the pathogenesis of this disease is also described herein.

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References

  1. Pearson, G. D., Veille, J. C., Rahimtoola, S., Hsia, J., Oakley, C. M., Hosenpud, J. D., et al. (2000), JAMA 283, 1183–1188.

    Article  PubMed  CAS  Google Scholar 

  2. Lampert, M. B. and Lang, R. M. (1995), Am. Heart J. 130, 860–870.

    Article  PubMed  CAS  Google Scholar 

  3. Cunningham, F. G., Pritchard, J. A., Hankins, G. D., Anderson, P. L., Lucas, M. J., and Armstrong, K. F. (1986), Obstet. Gynecol. 67, 157–168.

    Article  PubMed  CAS  Google Scholar 

  4. Knobel, B., Melamud, E., and Kishon, Y. (1984), Isr. J. Med. Sci. 20, 1061–1063.

    PubMed  CAS  Google Scholar 

  5. Lasinska-Kowara, M., Dudziak, M., and Suchorzewska, J. (2001), Can. J. Anaesth. 48, 773–777.

    PubMed  CAS  Google Scholar 

  6. Sakakibara, S., Sekiguchi, M., Konno, S., and Kusumoto, M. (1970), Am. Heart J. 80, 385–395.

    Article  PubMed  CAS  Google Scholar 

  7. Felker, G. M. and O'Connor, C. M. (2000), Am. Heart J. 140, 785–791.

    Article  PubMed  CAS  Google Scholar 

  8. Fett, J. D., Carraway, R. E., Dowell, D. L., King, M. E., and Pierre, R. A. (2002), Am. J. Obstet. Gyn. 186, 1005–1010.

    Article  Google Scholar 

  9. Mosmann, T. R. and Coffman, R. L. (1989), Ann. Rev. Immunol. 7, 145–173.

    Article  CAS  Google Scholar 

  10. Coffman, R. L., Seymour, B. W., Lebman, D. A., Hiraki, D. D., Christiansen, J. A., Shrader, B., et al. (1988), Immunol. Rev. 102, 5–58.

    Article  PubMed  CAS  Google Scholar 

  11. Cerwenka, A. and Swain, S. L. (1999), Microbes Infect. 1, 1291–1296.

    Article  PubMed  CAS  Google Scholar 

  12. Shevach, E. M. (2000), Annu. Rev. Immunol. 18, 423–449.

    Article  PubMed  CAS  Google Scholar 

  13. Shevach, E. M. (2001), J. Exp. Med. 193, F41-F46.

    Article  PubMed  CAS  Google Scholar 

  14. Han, X., Lundberg, P., Tanamachi, B., Openshaw, H., Longmate, J., and Cantin, E. (2001), J. Virol. 75, 3048–3052.

    Article  PubMed  CAS  Google Scholar 

  15. Bruland, T., Dai, H. Y., Lavik, L. A., Kristiansen, L. I., and Dalen, A. (2001), J. Gen. Virol. 82, 1821–1827.

    PubMed  CAS  Google Scholar 

  16. Barna, M., Komatsu, T., Bi, Z., and Reiss, C. S. (1996), J. Neuroimmunol. 67, 31–39.

    PubMed  Google Scholar 

  17. Gunderson, E. K., Garland, C., and Hourani, L. L. (2001), Mil. Med. 166, 544–549.

    PubMed  CAS  Google Scholar 

  18. Remoue, F., To Van, D., Schacht, A. M., Picquet, M., Garraud, O., Vercruysse, J., et al. (2001), Clin. Exp. Immunol. 124, 62–68.

    Article  PubMed  CAS  Google Scholar 

  19. Ortmeyer, L. E. (1979), women Health 4, 121–133.

    Article  PubMed  CAS  Google Scholar 

  20. Kaya, Z., Afanasyeva, M., Wang, Y., Dohmen, K. M., Schlichting, J., Tretter, T., et al. (2001), Nat. Immunol. 2, 739–745.

    Article  PubMed  CAS  Google Scholar 

  21. Shi, F., Ljunggren, H. G., and Sarvetnick, N. (2001) Trends Immunol. 22, 97–101.

    Article  PubMed  CAS  Google Scholar 

  22. Sarvetnick, N. and Fox, H. S. (1990), Mol. Biol. Med. 7, 323–331.

    PubMed  CAS  Google Scholar 

  23. Merrill, J. T., Dinu, A. R., and Lahita, R. G. (1996), Medscape Womens Health 1, 5.

    PubMed  Google Scholar 

  24. McMurray, R. W. (2001), Int. Immunopharmacol. 1, 995–1008.

    Article  PubMed  CAS  Google Scholar 

  25. Rider, V. and Abdou, N. I. (2001), Int. Immunopharmacol. 1, 1009–1024.

    Article  PubMed  CAS  Google Scholar 

  26. Tornwall, J., Carey, A. B., Fox, R. I., and Fox, H. S. (1999), J. Gend. Specif. Med. 2, 33–40.

    PubMed  CAS  Google Scholar 

  27. Caligiuri, G., Nicoletti, A., Zhou, X., Tornberg, I., and Hansson, G. K. (1999), Atherosclerosis 145 301–308.

    Article  PubMed  CAS  Google Scholar 

  28. Ahmed, S. A., Hissong, B. D., Verthelyi, D., Donner, K., Becker, K., and Karpuzoglu-Sahin, E. (1999), Environ. Health Perspect. 107, 681–686.

    Article  PubMed  CAS  Google Scholar 

  29. Holmdahl, R., Jansson, L., and Andersson, M. (1986), Arthritis Rheum. 29, 1501–1599.

    Article  PubMed  CAS  Google Scholar 

  30. Martin, J. T. (2000), Eur. J. Pharmacol. 405, 251–261.

    Article  PubMed  CAS  Google Scholar 

  31. Offner, H., Adlard, K., Zamora, A., and Vandenbark, A. A. (2000), J. Clin. Invest. 105, 1465–1472.

    Article  PubMed  CAS  Google Scholar 

  32. Rider, V., Foster, R. T., Evans, M., Suenaga, R., and Abdou, N. I. (1998), Clin. Immunol. Immunopathol. 89, 171–180.

    Article  PubMed  CAS  Google Scholar 

  33. Bebo, B. F., Jr., Schuster, J. C., Vandenbark, A. A., and Offner, H. (1999), J. Immunol. 162, 35–40.

    PubMed  CAS  Google Scholar 

  34. Da Silva, J. A. (1995), Ann. Rheum. Dis. 54, 6–16.

    PubMed  Google Scholar 

  35. Da Silva, J. A. (1999), Ann. NY Acad. Sci. 876, 102–117; discussion 117–118.

    Article  PubMed  Google Scholar 

  36. Gaillard, R. C. and Spinedi, E. (1998), Domest. Anim. Endocrinol. 15, 345–352.

    Article  PubMed  CAS  Google Scholar 

  37. Magiakou, M. A., Mastorakos, G., Webster, E., and Chrousos, G. P. (1997), Ann. NY Acad. Sci. 816, 42–56.

    Article  PubMed  CAS  Google Scholar 

  38. Olsen, N. J. and Kovacs, W. J. (1996), Endocr. Rev. 17, 369–384.

    Article  PubMed  CAS  Google Scholar 

  39. Schuurs, A. H. and Verheul, H. A. (1990), J. Steroid Biochem. 35, 157–172.

    Article  PubMed  CAS  Google Scholar 

  40. Slavkin, H. C. (1998), J. Am. Dent. Assoc. 129, 357–361.

    PubMed  CAS  Google Scholar 

  41. Fox, H. S. (1995), Ciba Found. Symp. 191, 203–211; discussion 211–217.

    PubMed  CAS  Google Scholar 

  42. Lucas, C., Bald, L. N., Martin, M. C., Jaffe, R. B., Drolet, D. W., Mora-Worms, M., et al. (1989), J. Endocrinol. 120, 449–457.

    Article  PubMed  CAS  Google Scholar 

  43. Medawar, P. B. (1954), Symp. Soc. Exp. Biol., vol. 7.

  44. Mellor, A. L. and Munn, D. H. (2001), Semin. Immunol. 13, 213–218.

    Article  PubMed  CAS  Google Scholar 

  45. Munn, D. H., Zhou, M., Attwood, J. T., Bondarev, I., Conway, S. J., Marshall, B., et al. (1998), Science 281, 1191–1193.

    Article  PubMed  CAS  Google Scholar 

  46. Matzinger, P. (1994), Annu. Rev. Immunol. 12, 991–1045.

    PubMed  CAS  Google Scholar 

  47. Bonney, E. A. and Matzinger, P. (1998), Nat. Med. 4, 1128–1129.

    Article  PubMed  CAS  Google Scholar 

  48. Clark, D. A. and Croitoru, K. (2001), Am. J. Reprod. Immunol. 45, 257–265.

    Article  PubMed  CAS  Google Scholar 

  49. Oakley, C. M., Gravanis, M. B., and Ansari, A. (1993), in Cardiovascular Disorders, Gravanis, M. B., ed. Mosby Yearbook Inc., St. Louis, pp. 210–253.

    Google Scholar 

  50. Herskowitz, A. and Baughman, K. (1993), in Cardiovascular Disorders, Gravanis, M. B., ed., Mosby Yearbook Inc., St. Louis, pp. 178–209.

    Google Scholar 

  51. Redondo, M. J., Rewers, M., Yu, L., Garg, S., Pilcher, C. C., Elliott, R. B., and Eisenbarth, G. S. (1999), BMJ 318, 698–702.

    PubMed  CAS  Google Scholar 

  52. Tomer, Y. and Davies, T. F. (1997), Baillieres Clin. Endocrinol. Metab. 11, 431–450.

    Article  PubMed  CAS  Google Scholar 

  53. Fett, J. D., Sundstrom, J. B., King, M. E., and Ansari, A. A. (2002) Int. J. Cardiol, in press.

  54. Lo, Y. M., Lo, Y. M., Lo, E. S., Watson, N., Noakes, L., Sargent, I. L., et al. (1996), Blood 88, 4390–4395.

    PubMed  CAS  Google Scholar 

  55. Prigoshin, N., Tambutti, M. L., Redal, M. A., Gorgorza, S., Lancuba, S. M., Nicholson, R., and Testa, R. (1999), J. Reprod. Immunol. 44, 41–54.

    Article  PubMed  CAS  Google Scholar 

  56. Starzl, T. E., Demetris, A. J., Murase, N., Ildstad, S., Ricordi, C., and Trucco, M. (1992), Lancet 339, 1579–1582.

    Article  PubMed  CAS  Google Scholar 

  57. Waldmann, H. (1999), Nat. Med. 5, 1245–1248.

    Article  PubMed  CAS  Google Scholar 

  58. Bianchi, D. W. (1998), J. Perinat. Med. 26, 175–185.

    PubMed  CAS  Google Scholar 

  59. Bianchi, D. W., Zickwolf, G. K., Weil, G. J., Sylvester, S., and DeMaria, M. A. (1996), Proc. Natl. Acad. Sci. USA 93, 705–708.

    Article  PubMed  CAS  Google Scholar 

  60. Aractingi, S., Berkane, N., Bertheau, P., Le Goue, C. Dausset, J., Uzan, S., and Carosella, E. D. Lancet 352, 1898–1901.

  61. Nelson, J. L., Furst, D. E., Maloney, S., Gooley, T., Evans, P. C., Smith, A., et al. (1998), Lancet 351, 559–562.

    Article  PubMed  CAS  Google Scholar 

  62. Tanaka, A., Lindor, K., Gish, R., Batts, K., Shiratori, Y., Omata, M., et al. (1999), Hepatology 30, 833–838.

    Article  PubMed  CAS  Google Scholar 

  63. Symmons, D. P., Bankhead, C. R., Harrison, B. J., Brennan, P., Barrett, E. M., Scott, D. G., and Silman, A. J. (1997), Arthritis Rheum. 40, 1955–1961.

    Article  PubMed  CAS  Google Scholar 

  64. Peng, T., Li, Y., Yang, Y., Niu, C., Morgan-Capner, P., Archard, L. C., and Zhang, H. (2000), J. Clin. Microbiol. 38, 3538–3543.

    PubMed  CAS  Google Scholar 

  65. Fett, J. D., Ansari, A. A., Sundstrom, J. B., and Combs, G. F., Jr. (2002) Int. J. Cardiol., submitted.

  66. Ansari, A. A., Neckelmann, N., Villinger, F., Leung, P., Danner, D. J., Brar, S. S., et al. (1994), J. Immunol. 153, 4754–4765.

    PubMed  CAS  Google Scholar 

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Ansari, A.A., Fett, J.D., Carraway, R.E. et al. Autoimmune mechanisms as the basis for human peripartum cardiomyopathy. Clinic Rev Allerg Immunol 23, 301–324 (2002). https://doi.org/10.1385/CRIAI:23:3:301

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