Immunity to heat shock proteins and pregnancy outcome

Abstract

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.

Silencing of chaperonin 21, that was differentially expressed in inflorescence of seedless and seeded grapes, promoted seed abortion in tobacco and tomato fruits

“…In higher plants, CPn60, a GroEL homologue, (Hemmingsen et al 1988) is composed of two subunits (Nishio et al 1999) and is located within the organelles. Chaperonins are critical for plant embryo and seed development (Zimmerman et al 1989;Marocco et al 1991;Nong et al 2002) as well as for mammalian embryogenesis (Loones and Morange 1998;Neuer et al 1998;Witkin et al 1999;Neuer et al 2000). Antisense of Cpn60b in plants influenced flowering and exhibited phenotypic alterations including reduced growth, stunting and leaf chlorosis (Zabaleta et al 1994).…”

Molecular mimicry and horror autotoxicus: do chlamydial infections elicit autoimmunity?

“…Indeed, the C. trachomatis and human versions of Hsp60 share close to 50% homology at the amino acid sequence level (Ref. 189). Studies of women with unexplained infertility and/or a history of spontaneous abortion have identified autoantibodies against human Hsp60 in those women with evidence of a previous infection with C. trachomatis ( Refs 30,31,189).…”

“…Studies of women with unexplained infertility and/or a history of spontaneous abortion have identified autoantibodies against human Hsp60 in those women with evidence of a previous infection with C. trachomatis ( Refs 30,31,189). Specifically, the presence of Hsp60 autoantibodies was correlated in these patients with a high level of humoral immune response to a particular highly conserved amino acid segment of the chlamydial Hsp60 (amino acids 260 -271) ( Refs 31,189); no relationship was identified between antibodies to the E. coli Hsp60 and the presence of Hsp60 autoantibodies in these patients. Heat shock proteins, including Hsp60, appear to be expressed at a reasonably high level in the early period of pregnancy by the embryo, and the presence of Hsp60 autoantibodies is postulated to lead to immune rejection of the embryo and thus spontaneous abortion (reviewed by Ref.…”

Host-Pathogen Co-Evolution: Chlamydia trachomatis Modulates Surface Ligand Expression in Genital Epithelial Cells to Evade Immune Recognition

“…Although circulating antibodies against C. trachomatis membrane associated proteins (MOMPs) have been linked to infertility, the presence of anti-CHSP60 antibodies appears to be more sensitive and specific for the disease (Linhares and Witkin 2010;Stephens, Aubuchon et al 2011). The presence of anti-CHSP60 IgA antibodies in the cervical secretions of women undergoing IVF has been associated with decreased live birth rates (Witkin 1999) and the presence of circulating IgG to CHSP60 in women with prior ectopic pregnancy has been linked repeat ectopic pregnancy and other adverse pregnancy outcomes (Sziller, Fedorcsak, et al 2008). To explain these findings, it has been hypothesized that prolonged exposure to CHSP60 may break tolerance to the human HSP60 that is normally expressed by normal human embryos (Linhares andWitkin 2010, Stephens, Aubuchon et al 2011).…”

“…The disease can result in scarring and pelvic organ disfigurement that lead to increases in ectopic pregnancy rates, tubal factor infertility (Hellstrom, Schachter et al 1987) and possibly early pregnancy wastage (Witkin 1999). If left untreated during pregnancy, chlamydial genital infections in women have been associated with preterm delivery (Rours, Duijts et al 2011).…”