Genome-wide identification of Chlamydia trachomatis antigens associated with tubal factor infertility

Abstract

Objective To identify C. trachomatis antigens that can be used to differentially diagnose tubal factor infertility in comparison to previously reported Heat Shock Protein 60 (HSP60). Design In Vitro Study Patients Infertile women with and without tubal pathology diagnosed laparoscopically. Setting Academic medical center. Main Outcome Measures Antibody responses to C. trachomatis in infertile women with or without tubal pathologies using a C. trachomatis genome-wide proteome array. Results Comparison of the antibody profiles revealed 30 C. trachomatis antigens that were preferentially recognized by tubal factor infertility women with a detection sensitivity and specificity of 80.6% and 56.5%, respectively, 10 of which showed 100% specificity. A combination of CT443 and CT381 antigens yielded the highest detection sensitivity (67.7%) while maintaining 100% specificity. Conclusion These findings have demonstrated that antibodies to CT443 and CT381, when used in combination, have higher sensitivity and specificity in predicting tubal factor infertility than other indicators for tubal factor infertility such as HSP60 antibodies (35.5%, 100%) or hysterosalpingogram (65%, 83%). Using a panel of C. trachomatis antigens to serologically diagnose tubal factor infertility can save the patients from undertaking expensive and invasive procedures for determining tubal pathology and choosing treatment plans.

Development and evaluation of a multi-antigen peptide ELISA for the diagnosis of Chlamydia trachomatis-related infertility in women

“…This lack of widespread implementation seems likely to be due to low specificity of the gold standard MIF and due to different perspectives on how the result can be best implemented into clinical protocol (Broeze et al, 2011). This has resulted in attempts to identify new antigens and develop new serological tests that could be used to specifically and sensitively identify chlamydial tubal infertility (Rodgers et al, 2010(Rodgers et al, , 2011Sanchez-Campillo et al, 1999;ForsbachBirk et al, 2010;Wills et al, 2009).…”

Intravenous Inoculation with Chlamydia muridarum Leads to a Long-Lasting Infection Restricted to the Gastrointestinal Tract

“…This is because a single inoculation of C. muridarum organisms in the mouse lower genital tract can cause hydrosalpinx and infertility (7)(8)(9), closely mimicking the tubal adhesion, hydrosalpinx, and infertility observed in women urogenitally infected with C. trachomatis (10)(11)(12). Although C. muridarum is not a natural sexually transmitted agent of mice, chlamydiologists have used this model not only to identify both chlamydial (13)(14)(15)(16)(17) and host (1,5,(18)(19)(20)(21)(22)(23)(24) pathogenic determinants but also to define the roles of ascending infection and tubal inflammation in chlamydial induction of hydrosalpinx (9,16,25,26).…”

Identification of Antigen-Specific Antibody Responses Associated with Upper Genital Tract Pathology in Mice Infected with Chlamydia muridarum

“…Chlamydial antigen-specific antibody responses have been correlated with tubal factor infertility (TFI) in women (6,46,47,53). In particular, an elevated level of anti-chlamydial heat shock protein 60 (HSP60) antibodies has been associated with tubal disease (3,6,19,26,27,30,35,54,55,60), which correlates with the elevated production of chlamydial HSP60 during persistent infection (21,30,35).…”

“…HSP60 may also induce T cell responses that contribute to the tubal damage (28,29). We have recently profiled human antibody responses to C. trachomatis infection and identified C. trachomatis antigens that are associated with TFI (46,47). However, because laparoscopic diagnosis of tubal pathologies is both invasive and expensive and recruiting sufficient numbers of patients who meet inclusion criteria has been difficult, there is still no reliable biomarker for predicting TFI, and the mechanisms of TFI remain unclear.…”