Circulating antibodies to a conserved epitope of the Chlamydia trachomatis 60 kDa heat shock protein (hsp60) in infertile couples and its relationship to antibodies to C.trachomatis surface antigens and the Escherichia coli and human HSP60

Abstract

To evaluate the relationship between immunity to specific regions of the Chlamydia trachomatis 60 kDa heat shock protein (hsp60), autoimmunity to human HSP60 and infertility, sera from 50 women and 45 men seen for an infertility evaluation were tested. Humoral immunity to human HSP60 was detected in 18% of women and 8.9% of men while antibodies to the Escherichia coli hsp60 were detected in 12% of women and 4.4% of men. These differences were not statistically significant. In contrast, antibodies to a synthetic peptide epitope of the chlamydial hsp60, encompassing amino acids 260-271 (chsp 260-271), were present in sera from 16 (32%) of the women but in only six (13.3%) of the men (P=0.03). Antibodies to chsp 260-271 were present in 11 out of 17 (64.7%) individuals with high titre (>1:160) immunoglobulin (Ig)G antibody to C.trachomatis surface antigens as opposed to only two out of 15 (13.3%) with low titre antibody and two out of of 17 (11.8%) with undetectable chlamydial antibody (P < 0.004). Antibodies to chsp 260-271 were also associated with humoral immunity to human HSP60. 50% of sera with, as opposed to only 18.6% of sera without, anti-human HSP60 IgG were positive for antibodies to chsp 260-271 (P=0.03). In contrast, there was no relationship found between immunity to the E.coli hsp60 and antibodies to human HSP60. Antibodies to chsp 260-271 were more prevalent in women with at least two spontaneous abortions (eight out of 13, 61.5%) than in women with other infertility diagnoses (six out of 35, 17.1%) (P=0.004). Thus, immunity to chsp 260-271 is more prevalent in women than in men, associated with autoimmunity to human HSP60 and may be an immunological marker for spontaneous abortion.

Chlamydial Hsp60-2 Is Iron Responsive in Chlamydia trachomatis Serovar E-Infected Human Endometrial Epithelial Cells In Vitro

“…In one study, cHsp60 serum antibodies were shown to be the best predicting factor for tubal factor infertility (51). Mapping of cHsp60-1 peptide epitopes in human sera has been done (50,54); it may be worthwhile to investigate whether peptides of cHsp60-2 and/or cHsp60-3 contribute to the generation of specific immunoglobulins. GroEL proteins are essential for bacterial growth and ensure that newly synthesized proteins are functional; expression of GroEL proteins increases in response to a variety of stresses, including heat shock and nutrient deprivation (56).…”

Autoimmunity to Human Heat Shock Protein 60, Chlamydia pneumoniae Infection, and Inflammation in Predicting Coronary Risk

“…25 Furthermore, it has been shown earlier that antibodies to the conservative peptide of C trachomatis Hsp60 are associated with autoimmunity to human Hsp60 and with infertility as chronic sequelae of C trachomatis infection. 26 Unfortunately, the role of the corresponding peptide of C pneumoniae Hsp60 in autoimmunity and in the development of atherosclerosis has not been studied.…”

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

“…This has largely resulted from a body of literature demonstrating high-titer human antibody responses to cHSP60 in patients with tubal pathology and additionally that, in several animal models, tissue pathology developed after repeated inoculations with cHSP60 protein (reviewed in reference 138). However, this mechanism is a subject of considerable controversy because of inconsistencies between the different published findings, i.e., problems with protein preparations that involved a hypersensitive detergent being used in some animal models and cross-reactivity or poor specificity of some of the antibody tests (141)(142)(143)(144)(145)(146)(147). On the other hand, there is no doubt that cHSP60 is a predominant chlamydial antigen that does frequently elicit an immune response.…”