Immune Recognition of the 60kD Heat Shock Protein: Implications for Subsequent Fertility

[摘要] The 60kD heat shock protein (hsp60) is a highly conserved protein and a dominant antigen ofmost pathogenic bacteria. In some women, chronic or repeated upper genital tract infections withChlamydia trachomatis, and possibly with other microorganisms, induces immune sensitization toepitopes of hsp60 that are present in both the microbial and human hsp60. Once a woman becomessensitized to these conserved epitpes, any subsequent induction of human or bacterial hsp60expression will reactivate hsp60-sensitized lymphocytes and initiate a pro-inflammatory immuneresponse. Hsp60 is expressed during the early stages of pregnancy, by both the embryo and thematernal decidua. We examined, therefore, whether women who were sensitized to hsp60 experiencedless successful pregnancy outcomes compared to women who were not sensitized to thisantigen. In women undergoing in vitro fertilization (IVF), the presence of cervical IgA antibodiesreactive with theC. trachomatishsp60 correlated with implantation failure after embryo transfer.Further analysis revealed that an immunodominant epitope for these IgA antibodies was an hsp60epitope shared betweenC. trachomatisand man. In subsequent studies of women not undergoingIVF, cervical IgA antibodies to the human hsp60 were identified in 13 of 91 reproductive agewomen. This antibody was most prevalent in those women with a history of primary infertility(p= 0.003). In addition, cervical anti-hsp60 IgA correlated with the detection of the pro-inflammatorycytokines interferon-γ (p= 0.001) and tumor necrosis factor-α (p= 0.02) in the cervix.Conversely, women with proven fertility had the highest prevalence of the anti-inflammatory cytokine,interleukin 10, in their cervices (p= 0.001). In an analysis of serum samples in a third study,women with a history of two or more consecutive first trimester spontaneous abortions had a higherprevalence (p= 0.01) of IgG antibodies to the human hsp60 (36.8%) than did age matched fertilewomen (11.1%) or women with primary infertility (11.8%). Immune sensitization to epitopes expressedby the human hsp60 may reduce the probability of a successful pregnancy outcome due toreactivation of hsp60-reactive lymphocytes, induction of a pro-inflammatory cytokine response andinterference with early embryo development and/or implantation.

[学科分类] 妇产科学