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. 1997;5(2):154–157. doi: 10.1155/S1064744997000239

Immune Sensitization to the 60 kD Heat Shock Protein and Pregnancy Outcome

A Neuer 1,✉, S Spandorfer 1, P Giraldo 1, C Mele 1, H C Liu 1, K Marzusch 1, D Kneissl 1, S S Witkin 1
PMCID: PMC2364576  PMID: 18476168

Abstract

Heat shock proteins are highly conserved proteins present in organisms ranging from bacteria to man. They are both dominant microbial immunogens and among the first proteins produced during mammalian embryo development. Since bacterial and human heat shock proteins share a high degree of amino acid sequence homology, it has been suggested that sensitization to bacterial heat shock proteins during an infection may result in autoimmunity to human heat shock proteins. Infertile couples seeking in vitro fertilization (IVF) may have been previously sensitized to bacterial heat shock proteins as a consequence of an asymptomatic upper genital tract infection. Due to daily clinical monitoring and precisely timed fertilization these patients are an ideal study group to investigate the effect of prior sensitization to heat shock proteins on preimplantation embryo development and implantation failure. Immune sensitization at the level of the cervix to the 60 kD heat shock protein (hsp60) has been associated with implantation failure in some IVF patients. Similarly, the highest prevalence of circulating hsp60 antibodies among IVF patients was found in the sera of women whose embryos failed to develop in vitro. To more directly assess whether humoral immunity to hsp60 influenced in vitro embryo development, a mouse embryo culture model was established. Monoclonal antibody to mammalian hsp60 markedly impaired mouse embryo development in vitro. These data suggest that immune sensitization to human hsp60, possibly developed as a consequence of infection, may adversely affect pregnancy outcome in some patients.

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Selected References

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  1. Alarcon-Segovia D., Ruiz-Argüelles A., Llorente L. Broken dogma: penetration of autoantibodies into living cells. Immunol Today. 1996 Apr;17(4):163–164. doi: 10.1016/s0167-5699(96)90258-3. [DOI] [PubMed] [Google Scholar]
  2. Bensaude O., Babinet C., Morange M., Jacob F. Heat shock proteins, first major products of zygotic gene activity in mouse embryo. Nature. 1983 Sep 22;305(5932):331–333. doi: 10.1038/305331a0. [DOI] [PubMed] [Google Scholar]
  3. Bensaude O., Morange M. Spontaneous high expression of heat-shock proteins in mouse embryonal carcinoma cells and ectoderm from day 8 mouse embryo. EMBO J. 1983;2(2):173–177. doi: 10.1002/j.1460-2075.1983.tb01401.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cates W., Jr, Wasserheit J. N. Genital chlamydial infections: epidemiology and reproductive sequelae. Am J Obstet Gynecol. 1991 Jun;164(6 Pt 2):1771–1781. doi: 10.1016/0002-9378(91)90559-a. [DOI] [PubMed] [Google Scholar]
  5. Chastant S., Christians E., Campion E., Renard J. P. Quantitative control of gene expression by nucleocytoplasmic interactions in early mouse embryos: consequence for reprogrammation by nuclear transfer. Mol Reprod Dev. 1996 Aug;44(4):423–432. doi: 10.1002/(SICI)1098-2795(199608)44:4<423::AID-MRD1>3.0.CO;2-N. [DOI] [PubMed] [Google Scholar]
  6. Christians E., Campion E., Thompson E. M., Renard J. P. Expression of the HSP 70.1 gene, a landmark of early zygotic activity in the mouse embryo, is restricted to the first burst of transcription. Development. 1995 Jan;121(1):113–122. doi: 10.1242/dev.121.1.113. [DOI] [PubMed] [Google Scholar]
  7. Christians E., Michel E., Renard J. P. Developmental control of heat shock and chaperone gene expression. Hsp 70 genes and heat shock factors during preimplantation phase of mouse development. Cell Mol Life Sci. 1997 Feb;53(2):168–178. doi: 10.1007/PL00000589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Heyborne K., Fu Y. X., Nelson A., Farr A., O'Brien R., Born W. Recognition of trophoblasts by gamma delta T cells. J Immunol. 1994 Oct 1;153(7):2918–2926. [PubMed] [Google Scholar]
  9. Kaufmann S. H. Heat shock proteins and the immune response. Immunol Today. 1990 Apr;11(4):129–136. doi: 10.1016/0167-5699(90)90050-j. [DOI] [PubMed] [Google Scholar]
  10. Kaufmann S. H., Schoel B., van Embden J. D., Koga T., Wand-Württenberger A., Munk M. E., Steinhoff U. Heat-shock protein 60: implications for pathogenesis of and protection against bacterial infections. Immunol Rev. 1991 Jun;121:67–90. doi: 10.1111/j.1600-065x.1991.tb00823.x. [DOI] [PubMed] [Google Scholar]
  11. Lamb J. R., Bal V., Mendez-Samperio P., Mehlert A., So A., Rothbard J., Jindal S., Young R. A., Young D. B. Stress proteins may provide a link between the immune response to infection and autoimmunity. Int Immunol. 1989;1(2):191–196. doi: 10.1093/intimm/1.2.191. [DOI] [PubMed] [Google Scholar]
  12. Legge M. Oocyte and zygote zona pellucida permeability to macromolecules. J Exp Zool. 1995 Feb 1;271(2):145–150. doi: 10.1002/jez.1402710210. [DOI] [PubMed] [Google Scholar]
  13. Loones M. T., Rallu M., Mezger V., Morange M. HSP gene expression and HSF2 in mouse development. Cell Mol Life Sci. 1997 Feb;53(2):179–190. doi: 10.1007/PL00000590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mincheva-Nilsson L., Baranov V., Yeung M. M., Hammarström S., Hammarström M. L. Immunomorphologic studies of human decidua-associated lymphoid cells in normal early pregnancy. J Immunol. 1994 Feb 15;152(4):2020–2032. [PubMed] [Google Scholar]
  15. Morrison R. P., Belland R. J., Lyng K., Caldwell H. D. Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein. J Exp Med. 1989 Oct 1;170(4):1271–1283. doi: 10.1084/jem.170.4.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Multhoff G., Botzler C., Jennen L., Schmidt J., Ellwart J., Issels R. Heat shock protein 72 on tumor cells: a recognition structure for natural killer cells. J Immunol. 1997 May 1;158(9):4341–4350. [PubMed] [Google Scholar]
  17. Sellens M. H., Jenkinson E. J. Permeability of the mouse zona pellucida to immunoglobulin. J Reprod Fertil. 1975 Jan;42(1):153–157. doi: 10.1530/jrf.0.0420153. [DOI] [PubMed] [Google Scholar]
  18. Shinnick T. M. Heat shock proteins as antigens of bacterial and parasitic pathogens. Curr Top Microbiol Immunol. 1991;167:145–160. doi: 10.1007/978-3-642-75875-1_9. [DOI] [PubMed] [Google Scholar]
  19. Soltys B. J., Gupta R. S. Immunoelectron microscopic localization of the 60-kDa heat shock chaperonin protein (Hsp60) in mammalian cells. Exp Cell Res. 1996 Jan 10;222(1):16–27. doi: 10.1006/excr.1996.0003. [DOI] [PubMed] [Google Scholar]
  20. Tabibzadeh S., Kong Q. F., Satyaswaroop P. G., Babaknia A. Heat shock proteins in human endometrium throughout the menstrual cycle. Hum Reprod. 1996 Mar;11(3):633–640. doi: 10.1093/humrep/11.3.633. [DOI] [PubMed] [Google Scholar]
  21. Witkin S. S., Jeremias J., Neuer A., David S., Kligman I., Toth M., Willner E., Witkin K. Immune recognition of the 60kD heat shock protein: implications for subsequent fertility. Infect Dis Obstet Gynecol. 1996;4(3):152–158. doi: 10.1155/S1064744996000336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Witkin S. S., Sultan K. M., Neal G. S., Jeremias J., Grifo J. A., Rosenwaks Z. Unsuspected Chlamydia trachomatis infection and in vitro fertilization outcome. Am J Obstet Gynecol. 1994 Nov;171(5):1208–1214. doi: 10.1016/0002-9378(94)90134-1. [DOI] [PubMed] [Google Scholar]

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