Cross-Reactivity between Chlamydia trachomatis Heat Shock Protein 10 and Early Pregnancy Factor

Abstract

Chlamydia trachomatis heat shock protein 10 (Chsp10) is associated with chronic genital tract infection with C. trachomatis. Chsp10 is homologous to human chaperonin 10 (Cpn10) and early pregnancy factor (EPF), a form of human Cpn10 that is specifically secreted at the start of pregnancy. We investigated cross-reactions between serum anti-Chsp10 antibodies and anti-EPF antibodies in pregnant and nonpregnant patients. Pregnancy was found to be associated with the presence of anti-EPF antibodies, which are specifically induced in pregnant women with a history of C. trachomatis infection, and with the presence of serum anti-Chsp10 antibodies. We also found that infertility was associated with the presence of anti-Chsp10 and anti-EPF antibodies. The HLA class II haplotype DR8 DQ4 was associated with the presence of anti-Chsp10 antibodies but not of anti-EPF antibodies.Heat shock proteins (Hsps) are a highly conserved group of polypeptides that are produced under a variety of stress conditions to preserve cellular functions. The major Hsps are molecular chaperones that direct the folding and assembly of polypeptides in the cell (11). Early pregnancy factor (EPF) has been identified as a homologue of chaperonin 10 (Cpn10). It belongs to the heat shock protein family, but unlike other members of this family, EPF is detected outside the cell. EPF has immunosuppressant (17) and growth factor properties (19), rendering it essential for the growth and survival of the embryo during the pre-and postimplantation periods (2, 3). The passive immunization of pregnant mice with anti-EPF antibodies leads to the retardation of embryonic development and/or inhibition of implantation.The partial amino acid sequences obtained for platelet-derived EPF are 100% identical to the corresponding sequences of human mitochondrial Cpn10 (8, 14) and 33.3% identical to those of the Chlamydia trachomatis chlamydial Hsp 10 (Chsp10) (12) (Fig. 1). The 10-kDa Hsp of C. trachomatis has been shown to be associated with chronic infection and sequelae, such as ectopic pregnancy (4). Hsp synthesis is induced in microbial pathogens during infection (6). Microbial Hsps are highly immunogenic and display a high level of conservation through evolution; in addition, immune cells have been shown to recognize both microbial and self-Hsp (22). Therefore, cross-reactions may occur between C. trachomatis Chsp10 and human extracellular EPF. Such cross-reactions might interfere with EPF function at the start of pregnancy, thereby playing a role in C. trachomatis-associated female infertility.We studied a population of 716 women in the first trimester of pregnancy. We used a C. trachomatis-specific molecular biology detection technique and investigated C. trachomatis species-specific and Chsp10-specific serum antibody responses. We tested 230 of the patients for immunoglobulin G (IgG) antibodies specifically recognizing two EPF-derived synthetic peptides. As EPF is essential for embryo implantation and survival, we also investigated a population of 210 women consulti...

Mucosal and peripheral immune responses to chlamydial heat shock proteins in women infected with Chlamydia trachomatis

“…cHSP10 is associated with chronic genital tract infection and is homologous to human chaperonin (Cpn10) and early pregnancy factor (EPF), a form of Cpn10 that is secreted especially at the start of pregnancy. It has been reported previously that infertility was associated with the presence of anti‐cHSP10 and anti‐EPF antibodies in serum [20]. A study by La Verda et al .…”

“…cHSP10 is associated with chronic genital tract infection and is homologous to human chaperonin (Cpn10) and early pregnancy factor (EPF), a form of Cpn10 that is secreted especially at the start of pregnancy. It has been reported previously that infertility was associated with the presence of anti-cHSP10 and anti-EPF antibodies in serum [20]. A study by La Verda et al [17] demonstrated that women with acute infection and tubal factor infertility (TFI) recognized cHSP10 more frequently, with infertile women having greater seroreactivity to cHSP10 than acutely infected women.…”

Association between anti-chlamydial immunity and IVF outcome

“…might render less receptive for implantation or successful placentation. Second, antibodies to cHSP60 may recognize conserved epitopes that are present in the homologous human, microbial HSP60 or early pregnancy factor [29,30]. This selfimmune response, triggered by previous exposure to C. trachomatis, might be related to IVF failure by blocking embryo development or implantation.…”

Molecular mimicry: An explanation for autoimmune diseases and infertility

“…The similarity between human and chlamydial HSP60 leads to the development of antibodies against cHSP60 in the serum and follicular fluid of females exposed to C. trachomatis which might negatively affect pregnancy outcomes and embryonal growth. Cross‐reactivity has also been reported between cHSP10 and human early pregnancy factor (EPF), an embryonic protein, which is responsible for abortions …”