Immunity to Heat Shock Proteins and Pregnancy Outcome

Heat shock proteins are among the first proteins produced by the zygote after fertilization. In addition, the maternal decidua also expresses heat shock proteins during the early stages of pregnancy. Autoimmunity to heat shock proteins is not typically evident in healthy women of reproductive age. However, a chronic microbial infection, such as an asymptomatic Chlamydia trachomatis upper genital tract infection, results in prolonged exposure of the immune system to the microbial 60 kDa heat shock protein (hsp60). This may result in immunity to conserved hsp60 epitopes and subsequent autoimmunity to self hsp60. Women undergoing in vitro fertilization (IVF) who never realized they had a chlamydial infection but who were positive for cervical antichlamydial immunoglobulin A (IgA) antibodies had a much lower pregnancy rate than did women who were negative for these antibodies. Furthermore, cervical IgA antibodies to the chlamydial hsp60, as well as to a synthetic peptide corresponding to an hsp60 epitope present in both the chlamydial and human hsp60, also correlated with IVF failure. In vitro incubation of newly fertilized human embryos in medium containing maternal serum was shown to be deleterious to embryo development if the sera was positive for antibodies reactive with human hsp60. In another study, the ability of human hsp60 to elicit a lymphocyte proliferative response (cell-mediated immunity) correlated with a history of spontaneous early stage pregnancy loss. Thus, autoimmunity to hsp60 might increase susceptibility to early stage pregnancy loss.