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

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.