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. 1997 Jun;65(6):2250–2253. doi: 10.1128/iai.65.6.2250-2253.1997

Evidence of genetic susceptibility to Chlamydia trachomatis-induced pelvic inflammatory disease in the pig-tailed macaque.

A B Lichtenwalner 1, D L Patton 1, Y T Cosgrove Sweeney 1, L K Gaur 1, W E Stamm 1
PMCID: PMC175311  PMID: 9169759

Abstract

The macaque model of chlamydial pelvic inflammatory disease (PID) demonstrates individual variability in the time of onset of intrapelvic adhesions. Some animals develop adhesions rapidly, within 2 weeks after a single tubal inoculation with Chlamydia trachomatis, while in others, adhesions are not observed until 2 weeks after a second tubal inoculation. To test whether this variability correlates with major histocompatibility complex (MHC) class I haplotype, we used macaque alloantisera and mouse anti-HLA monoclonal antibodies to determine the MHC class I haplotypes of 44 C. trachomatis-infected macaques (Macaca nemestrina). Macaques developing gross tubal adhesions after the first chlamydial inoculation were classified as susceptible (n = 29), while those not developing adhesions until after the second chlamydial inoculation were classified as relatively resistant (n = 15), to adhesion formation. Three antibody specificities correlated with susceptibility (odds ratio [OR] 5.2, P < 0.01; OR 6.1 and 4.3, P < 0.05), and two correlated with relative resistance to adhesions (OR 0.1, P < 0.05; OR 0.2, P < 0.01). Because several of these antibodies are cross-reactive, as many as five different MHC class I alleles (three increasing and two decreasing ORs) or as few as two different MHC class I alleles (one increasing and one decreasing OR) could be correlated with risk of adhesion formation. We conclude that in macaques, susceptibility or relative resistance to rapid formation of tubal adhesions is correlated with expression of MHC class I alleles, consistent with reports of MHC class I restriction of chlamydial immunopathology in humans.

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Selected References

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  1. Gaur L. K., Antonelli P., Clark E. A., Hansen J. A. Evolution of HLA class I epitopes defined by murine monoclonal antibodies: distribution in macaques. Hum Immunol. 1986 Dec;17(4):406–415. doi: 10.1016/0198-8859(86)90300-9. [DOI] [PubMed] [Google Scholar]
  2. Gaur L. K., Bowden D. M., Tsai C. C., Davis A., Clark E. A. The major histocompatibility complex, MnLA, of pigtailed macaques: definition of fifteen specificities. Hum Immunol. 1989 Apr;24(4):277–294. doi: 10.1016/0198-8859(89)90021-9. [DOI] [PubMed] [Google Scholar]
  3. Gaur L. K., Heise E. R., Hansen J. A., Clark E. A. Conservation of HLA class I private epitopes in macaques. Immunogenetics. 1988;27(5):356–362. doi: 10.1007/BF00395131. [DOI] [PubMed] [Google Scholar]
  4. Gaur L. K., Heise E. R., Thurtle P. S., Nepom G. T. Conservation of the HLA-DQB2 locus in nonhuman primates. J Immunol. 1992 Feb 1;148(3):943–948. [PubMed] [Google Scholar]
  5. Gaur L. K., Nepom G. T. Ancestral major histocompatibility complex DRB genes beget conserved patterns of localized polymorphisms. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5380–5383. doi: 10.1073/pnas.93.11.5380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Keever C. A., Heise E. R. The major histocompatibility complex (CyLA) of the cynomolgus monkey. I. Serologic definition of 21 specificities. Hum Immunol. 1983 Jul;7(3):131–149. doi: 10.1016/s0198-8859(83)80002-0. [DOI] [PubMed] [Google Scholar]
  7. Kimani J., Maclean I. W., Bwayo J. J., MacDonald K., Oyugi J., Maitha G. M., Peeling R. W., Cheang M., Nagelkerke N. J., Plummer F. A. Risk factors for Chlamydia trachomatis pelvic inflammatory disease among sex workers in Nairobi, Kenya. J Infect Dis. 1996 Jun;173(6):1437–1444. doi: 10.1093/infdis/173.6.1437. [DOI] [PubMed] [Google Scholar]
  8. Mabey D. C., Bailey R. L., Ward M. E., Whittle H. C. A longitudinal study of trachoma in a Gambian village: implications concerning the pathogenesis of chlamydial infection. Epidemiol Infect. 1992 Apr;108(2):343–351. doi: 10.1017/s0950268800049815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Morrison L. A., Lukacher A. E., Braciale V. L., Fan D. P., Braciale T. J. Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones. J Exp Med. 1986 Apr 1;163(4):903–921. doi: 10.1084/jem.163.4.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Patton D. L., Kuo C. C., Wang S. P., Halbert S. A. Distal tubal obstruction induced by repeated Chlamydia trachomatis salpingeal infections in pig-tailed macaques. J Infect Dis. 1987 Jun;155(6):1292–1299. doi: 10.1093/infdis/155.6.1292. [DOI] [PubMed] [Google Scholar]
  11. Patton D. L., Sweeney Y. C., Bohannon N. J., Clark A. M., Hughes J. P., Cappuccio A., Campbell L. A., Stamm W. E. Effects of doxycycline and antiinflammatory agents on experimentally induced chlamydial upper genital tract infection in female macaques. J Infect Dis. 1997 Mar;175(3):648–654. doi: 10.1093/infdis/175.3.648. [DOI] [PubMed] [Google Scholar]
  12. Patton D. L., Sweeney Y. C., Rabe L. K., Hillier S. L. The vaginal microflora of pig-tailed macaques and the effects of chlorhexidine and benzalkonium on this ecosystem. Sex Transm Dis. 1996 Nov-Dec;23(6):489–493. doi: 10.1097/00007435-199611000-00009. [DOI] [PubMed] [Google Scholar]
  13. Schwimmbeck P. L., Yu D. T., Oldstone M. B. Autoantibodies to HLA B27 in the sera of HLA B27 patients with ankylosing spondylitis and Reiter's syndrome. Molecular mimicry with Klebsiella pneumoniae as potential mechanism of autoimmune disease. J Exp Med. 1987 Jul 1;166(1):173–181. doi: 10.1084/jem.166.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sieper J., Kingsley G., Palacios-Boix A., Pitzalis C., Treharne J., Hughes R., Keat A., Panayi G. S. Synovial T lymphocyte-specific immune response to Chlamydia trachomatis in Reiter's disease. Arthritis Rheum. 1991 May;34(5):588–598. doi: 10.1002/art.1780340511. [DOI] [PubMed] [Google Scholar]
  15. Slierendregt B. L., Bontrop R. E. Current knowledge on the major histocompatibility complex class II region in non-human primates. Eur J Immunogenet. 1994 Oct;21(5):391–402. doi: 10.1111/j.1744-313x.1994.tb00212.x. [DOI] [PubMed] [Google Scholar]
  16. Starnbach M. N., Bevan M. J., Lampe M. F. Protective cytotoxic T lymphocytes are induced during murine infection with Chlamydia trachomatis. J Immunol. 1994 Dec 1;153(11):5183–5189. [PubMed] [Google Scholar]
  17. TERASAKI P. I., MCCLELLAND J. D. MICRODROPLET ASSAY OF HUMAN SERUM CYTOTOXINS. Nature. 1964 Dec 5;204:998–1000. doi: 10.1038/204998b0. [DOI] [PubMed] [Google Scholar]
  18. Tuffrey M., Alexander F., Woods C., Taylor-Robinson D. Genetic susceptibility to chlamydial salpingitis and subsequent infertility in mice. J Reprod Fertil. 1992 May;95(1):31–38. doi: 10.1530/jrf.0.0950031. [DOI] [PubMed] [Google Scholar]
  19. Turner V. M., West S. K., Muñoz B., Katala S. J., Taylor H. R., Halsey N., Mmbaga B. B. Risk factors for trichiasis in women in Kongwa, Tanzania: a case-control study. Int J Epidemiol. 1993 Apr;22(2):341–347. doi: 10.1093/ije/22.2.341. [DOI] [PubMed] [Google Scholar]
  20. Van Voorhis W. C., Barrett L. K., Sweeney Y. T., Kuo C. C., Patton D. L. Analysis of lymphocyte phenotype and cytokine activity in the inflammatory infiltrates of the upper genital tract of female macaques infected with Chlamydia trachomatis. J Infect Dis. 1996 Sep;174(3):647–650. doi: 10.1093/infdis/174.3.647. [DOI] [PubMed] [Google Scholar]
  21. WOOLF B. On estimating the relation between blood group and disease. Ann Hum Genet. 1955 Jun;19(4):251–253. doi: 10.1111/j.1469-1809.1955.tb01348.x. [DOI] [PubMed] [Google Scholar]
  22. Zhong G., Brunham R. C. Antibody responses to the chlamydial heat shock proteins hsp60 and hsp70 are H-2 linked. Infect Immun. 1992 Aug;60(8):3143–3149. doi: 10.1128/iai.60.8.3143-3149.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

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