Reduced Endometrial Ascension and Enhanced Reinfection Associated With Immunoglobulin G Antibodies to Specific Chlamydia trachomatis Proteins in Women at Risk for Chlamydia

Abstract

Background Previous research revealed antibodies targeting Chlamydia trachomatis (CT) elementary bodies was not associated with reduced endometrial or incident infection in CT-exposed women. However, data on the role of CT protein-specific antibodies in protection are limited. Methods A whole-proteome CT array screening serum pools from CT-exposed women identified 121 immunoprevalent proteins. Individual sera were probed using a focused array. IgG antibody frequencies and endometrial or incident infection relationships were examined using Wilcoxon Rank sum test. The impact of breadth and magnitude of protein-specific IgGs on ascension and incident infection were examined using multivariable stepwise logistic regression. Complementary RNA-sequencing quantified CT gene transcripts in cervical swabs from infected women. Results IgG to Pgp3 and CT005 were associated with reduced endometrial infection; anti-CT443, -CT486 and -CT123 were associated with increased incident infection. Increased breadth of protein recognition did not however predict protection from endometrial or incident infection. mRNAs for immunoprevalent CT proteins were highly abundant in the cervix. Conclusions Protein-specific CT antibodies are not sufficient to protect against ascending or incident infection but broad recognition of CT proteins by IgG correlates with cervical CT gene transcript abundance, suggesting CT protein abundance correlates with immunogenicity and signifies their potential as vaccine candidates.

A Machine Learning-Based Analytic Pipeline Applied to Clinical and Serum IgG Immunoproteome Data To Predict Chlamydia trachomatis Genital Tract Ascension and Incident Infection in Women

“…Data from 222 women, 144 infected and 78 uninfected, were used in this study. The sociodemographic characteristics of participants have been described previously ( 13 ). Women in this study were young (median age, 21 years; range, 18 to 35 years), and the majority of them were single, were African American, and were high school graduates or had some college education.…”

“…Among women without Ct infection at enrollment, 9 (18%) were F/U+ and 42 (82%) were F/U−. Seropositivity profiles of 121 Ct protein-specific serum IgGs ( 13 ), previously identified clinical risk factors for ascension (oral contraceptives and gonorrhea), and incident infection (gonorrhea, age, cervical infection at enrollment, and sex with new, uncircumcised, or infected partners) ( 12 ) were subjected to biomarker analysis.…”

“…We generated a case study by applying this ML pipeline to prediction of outcomes of Chlamydia trachomatis ( Ct ) infection, using clinical and immunoproteome antibody data collected from a unique and well-defined longitudinal cis-gender female cohort with high risk of Ct exposure and endometrial Ct infection status determined by analysis of biopsy specimens ( 12 , 13 ). Ct infection is the leading bacterial sexually transmitted infection in the United States.…”

“…Ct expresses over 875 proteins ( 16 ). Applying logistic regression to serum IgG-binding data from a whole-proteome Ct array that screened serum pools from Ct -exposed women, we identified antibodies to some Ct proteins that weakly associated with decreased risk of ascension and others associated with increased risk for incident infection ( 13 ). In addition, we previously determined select sociodemographic, coinfection, and behavioral risk factors contributing to ascending and incident infection ( 12 ).…”

Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity

“…In about 50% of women (1), infection can ascend from the cervix to the upper genital tract (uterus and fallopian tubes), potentially resulting in pelvic inflammatory disease (PID) and leading to devastating long-term sequela including chronic pelvic pain and infertility (2). In previous studies we have identified behavioral, biological, blood transcriptional, cervical cytokine, and Ct antigen-specific T cell and antibody responses, associated with altered risk of endometrial Ct infection (1,(3)(4)(5)(6). However, a major research gap that remains is the lack of biomarker(s) that can identify women at elevated risk of disease.…”