Abstract
Chlamydia trachomatis (CT) infections of the female genital tract, although frequently asymptomatic, are a major cause of fallopian-tube occlusion and infertility. Early stage pregnancy loss may also be due to an unsuspected and undetected CT infection. In vitro and in vivo studies have demonstrated that this organism can persist in the female genital tract in a form undetectable by culture. The mechanism of tubal damage as well as the rejection of an embryo may involve an initial immune sensitization to the CT 60 kD heat shock protein (HSP), followed by a reactivation of HSP-sensitized lymphocytes in response to the human HSP and the subsequent release of inflammatory cytokines. The periodic induction of human HSP expression by various microorganisms or by noninfectious mechanisms in the fallopian tubes of women sensitized to the CT HSP may eventually result in tubal scarring and occlusion. Similarly, an immune response to human HSP expression during the early stages of pregnancy may interfere with the immune regulatory mechanisms required for the maintenance of a semiallogeneic embryo.
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- Beatty W. L., Byrne G. I., Morrison R. P. Morphologic and antigenic characterization of interferon gamma-mediated persistent Chlamydia trachomatis infection in vitro. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3998–4002. doi: 10.1073/pnas.90.9.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boehme M., Donat H. Identification of lymphocyte subsets in the human fallopian tube. Am J Reprod Immunol. 1992 Sep;28(2):81–84. doi: 10.1111/j.1600-0897.1992.tb00764.x. [DOI] [PubMed] [Google Scholar]
- Brunham R. C., Maclean I. W., Binns B., Peeling R. W. Chlamydia trachomatis: its role in tubal infertility. J Infect Dis. 1985 Dec;152(6):1275–1282. doi: 10.1093/infdis/152.6.1275. [DOI] [PubMed] [Google Scholar]
- Cates W., Jr, Joesoef M. R., Goldman M. B. Atypical pelvic inflammatory disease: can we identify clinical predictors? Am J Obstet Gynecol. 1993 Aug;169(2 Pt 1):341–346. doi: 10.1016/0002-9378(93)90085-w. [DOI] [PubMed] [Google Scholar]
- Grifo J. A., Jeremias J., Ledger W. J., Witkin S. S. Interferon-gamma in the diagnosis and pathogenesis of pelvic inflammatory disease. Am J Obstet Gynecol. 1989 Jan;160(1):26–31. doi: 10.1016/0002-9378(89)90080-x. [DOI] [PubMed] [Google Scholar]
- Gump D. W., Gibson M., Ashikaga T. Evidence of prior pelvic inflammatory disease and its relationship to Chlamydia trachomatis antibody and intrauterine contraceptive device use in infertile women. Am J Obstet Gynecol. 1983 May 15;146(2):153–159. doi: 10.1016/0002-9378(83)91044-x. [DOI] [PubMed] [Google Scholar]
- Handsfield H. H., Jasman L. L., Roberts P. L., Hanson V. W., Kothenbeutel R. L., Stamm W. E. Criteria for selective screening for Chlamydia trachomatis infection in women attending family planning clinics. JAMA. 1986 Apr 4;255(13):1730–1734. [PubMed] [Google Scholar]
- 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]
- Hillis S. D., Nakashima A., Marchbanks P. A., Addiss D. G., Davis J. P. Risk factors for recurrent Chlamydia trachomatis infections in women. Am J Obstet Gynecol. 1994 Mar;170(3):801–806. doi: 10.1016/s0002-9378(94)70286-1. [DOI] [PubMed] [Google Scholar]
- Holland S. M., Hudson A. P., Bobo L., Whittum-Hudson J. A., Viscidi R. P., Quinn T. C., Taylor H. R. Demonstration of chlamydial RNA and DNA during a culture-negative state. Infect Immun. 1992 May;60(5):2040–2047. doi: 10.1128/iai.60.5.2040-2047.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones R. B., Ardery B. R., Hui S. L., Cleary R. E. Correlation between serum antichlamydial antibodies and tubal factor as a cause of infertility. Fertil Steril. 1982 Nov;38(5):553–558. doi: 10.1016/s0015-0282(16)46634-3. [DOI] [PubMed] [Google Scholar]
- Keat A., Thomas B., Dixey J., Osborn M., Sonnex C., Taylor-Robinson D. Chlamydia trachomatis and reactive arthritis: the missing link. Lancet. 1987 Jan 10;1(8524):72–74. doi: 10.1016/s0140-6736(87)91910-6. [DOI] [PubMed] [Google Scholar]
- Kiessling R., Grönberg A., Ivanyi J., Söderström K., Ferm M., Kleinau S., Nilsson E., Klareskog L. Role of hsp60 during autoimmune and bacterial inflammation. Immunol Rev. 1991 Jun;121:91–111. doi: 10.1111/j.1600-065x.1991.tb00824.x. [DOI] [PubMed] [Google Scholar]
- Luis A. M., Alconada A., Cuezva J. M. The alpha regulatory subunit of the mitochondrial F1-ATPase complex is a heat-shock protein. Identification of two highly conserved amino acid sequences among the alpha-subunits and molecular chaperones. J Biol Chem. 1990 May 15;265(14):7713–7716. [PubMed] [Google Scholar]
- Mahony J. B., Luinstra K. E., Sellors J. W., Pickard L., Chong S., Jang D., Chernesky M. A. Role of confirmatory PCRs in determining performance of Chlamydia Amplicor PCR with endocervical specimens from women with a low prevalence of infection. J Clin Microbiol. 1994 Oct;32(10):2490–2493. doi: 10.1128/jcm.32.10.2490-2493.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCormack W. M., Alpert S., McComb D. E., Nichols R. L., Semine D. Z., Zinner S. H. Fifteen-month follow-up study of women infected with Chlamydia trachomatis. N Engl J Med. 1979 Jan 18;300(3):123–125. doi: 10.1056/NEJM197901183000305. [DOI] [PubMed] [Google Scholar]
- 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]
- Munoz M. G., Witkin S. S. Autoimmunity to spermatozoa, asymptomatic Chlamydia trachomatis genital tract infection and gamma delta T lymphocytes in seminal fluid from the male partners of couples with unexplained infertility. Hum Reprod. 1995 May;10(5):1070–1074. doi: 10.1093/oxfordjournals.humrep.a136096. [DOI] [PubMed] [Google Scholar]
- Ossewaarde J. M., Rieffe M., Rozenberg-Arska M., Ossenkoppele P. M., Nawrocki R. P., van Loon A. M. Development and clinical evaluation of a polymerase chain reaction test for detection of Chlamydia trachomatis. J Clin Microbiol. 1992 Aug;30(8):2122–2128. doi: 10.1128/jcm.30.8.2122-2128.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patton D. L., Askienazy-Elbhar M., Henry-Suchet J., Campbell L. A., Cappuccio A., Tannous W., Wang S. P., Kuo C. C. Detection of Chlamydia trachomatis in fallopian tube tissue in women with postinfectious tubal infertility. Am J Obstet Gynecol. 1994 Jul;171(1):95–101. doi: 10.1016/s0002-9378(94)70084-2. [DOI] [PubMed] [Google Scholar]
- Patton D. L., Sweeney Y. T., Kuo C. C. Demonstration of delayed hypersensitivity in Chlamydia trachomatis salpingitis in monkeys: a pathogenic mechanism of tubal damage. J Infect Dis. 1994 Mar;169(3):680–683. doi: 10.1093/infdis/169.3.680. [DOI] [PubMed] [Google Scholar]
- Pelvic inflammatory disease. Research directions in the 1990s. Expert Committee on Pelvic Inflammatory Disease. Sex Transm Dis. 1991 Jan-Mar;18(1):46–64. doi: 10.1097/00007435-199101000-00011. [DOI] [PubMed] [Google Scholar]
- Rahm V. A., Odlind V., Pettersson R. Chlamydia trachomatis in sexually active teenage girls. Factors related to genital chlamydial infection: a prospective study. Genitourin Med. 1991 Aug;67(4):317–321. doi: 10.1136/sti.67.4.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Retzlaff C., Yamamoto Y., Hoffman P. S., Friedman H., Klein T. W. Bacterial heat shock proteins directly induce cytokine mRNA and interleukin-1 secretion in macrophage cultures. Infect Immun. 1994 Dec;62(12):5689–5693. doi: 10.1128/iai.62.12.5689-5693.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stergachis A., Scholes D., Heidrich F. E., Sherer D. M., Holmes K. K., Stamm W. E. Selective screening for Chlamydia trachomatis infection in a primary care population of women. Am J Epidemiol. 1993 Aug 1;138(3):143–153. doi: 10.1093/oxfordjournals.aje.a116840. [DOI] [PubMed] [Google Scholar]
- Toth M., Jeremias J., Ledger W. J., Witkin S. S. In vivo tumor necrosis factor production in women with salpingitis. Surg Gynecol Obstet. 1992 May;174(5):359–362. [PubMed] [Google Scholar]
- Toye B., Laferrière C., Claman P., Jessamine P., Peeling R. Association between antibody to the chlamydial heat-shock protein and tubal infertility. J Infect Dis. 1993 Nov;168(5):1236–1240. doi: 10.1093/infdis/168.5.1236. [DOI] [PubMed] [Google Scholar]
- Wagar E. A., Schachter J., Bavoil P., Stephens R. S. Differential human serologic response to two 60,000 molecular weight Chlamydia trachomatis antigens. J Infect Dis. 1990 Oct;162(4):922–927. doi: 10.1093/infdis/162.4.922. [DOI] [PubMed] [Google Scholar]
- Weinstock H. S., Bolan G. A., Kohn R., Balladares C., Back A., Oliva G. Chlamydia trachomatis infection in women: a need for universal screening in high prevalence populations? Am J Epidemiol. 1992 Jan 1;135(1):41–47. doi: 10.1093/oxfordjournals.aje.a116200. [DOI] [PubMed] [Google Scholar]
- Witkin S. S., Chaudhry A. Circulating interferon-gamma in women sensitized to sperm: new mechanisms of infertility. Fertil Steril. 1989 Nov;52(5):867–869. doi: 10.1016/s0015-0282(16)53056-8. [DOI] [PubMed] [Google Scholar]
- Witkin S. S., David S. S. Effect of sperm antibodies on pregnancy outcome in a subfertile population. Am J Obstet Gynecol. 1988 Jan;158(1):59–62. doi: 10.1016/0002-9378(88)90776-4. [DOI] [PubMed] [Google Scholar]
- Witkin S. S., Jeremias J., Grifo J. A., Ledger W. J. Detection of Chlamydia trachomatis in semen by the polymerase chain reaction in male members of infertile couples. Am J Obstet Gynecol. 1993 May;168(5):1457–1462. doi: 10.1016/s0002-9378(11)90781-9. [DOI] [PubMed] [Google Scholar]
- Witkin S. S., Jeremias J., Toth M., Ledger W. J. Cell-mediated immune response to the recombinant 57-kDa heat-shock protein of Chlamydia trachomatis in women with salpingitis. J Infect Dis. 1993 Jun;167(6):1379–1383. doi: 10.1093/infdis/167.6.1379. [DOI] [PubMed] [Google Scholar]
- Witkin S. S., Jeremias J., Toth M., Ledger W. J. Proliferative response to conserved epitopes of the Chlamydia trachomatis and human 60-kilodalton heat-shock proteins by lymphocytes from women with salpingitis. Am J Obstet Gynecol. 1994 Aug;171(2):455–460. doi: 10.1016/0002-9378(94)90282-8. [DOI] [PubMed] [Google Scholar]
- Witkin S. S., Kligman I., Grifo J. A., Rosenwaks Z. Chlamydia trachomatis detected by polymerase chain reaction in cervices of culture-negative women correlates with adverse in vitro fertilization outcome. J Infect Dis. 1995 Jun;171(6):1657–1659. doi: 10.1093/infdis/171.6.1657. [DOI] [PubMed] [Google Scholar]
- Witkin S. S. Mechanisms of active suppression of the immune response to spermatozoa. Am J Reprod Immunol Microbiol. 1988 Jun;17(2):61–64. doi: 10.1111/j.1600-0897.1988.tb00204.x. [DOI] [PubMed] [Google Scholar]
- Witkin S. S. Production of interferon gamma by lymphocytes exposed to antibody-coated spermatozoa: a mechanism for sperm antibody production in females. Fertil Steril. 1988 Sep;50(3):498–502. doi: 10.1016/s0015-0282(16)60140-1. [DOI] [PubMed] [Google Scholar]
- 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]
- Wølner-Hanssen P., Mårdh P. A. In vitro tests of the adherence of Chlamydia trachomatis to human spermatozoa. Fertil Steril. 1984 Jul;42(1):102–107. doi: 10.1016/s0015-0282(16)47966-5. [DOI] [PubMed] [Google Scholar]