Chlamydial Pgp3 Seropositivity and Population-Attributable Fraction Among Women With Tubal Factor Infertility

Anyalechi, Gloria E; Hong, Jaeyoung; Kirkcaldy, Robert D.; Wiesenfeld, Harold C.; Horner, Patrick J; Wills, Gillian; McClure, Myra O.; Hammond, Karen R.; Haggerty, Catherine L.; Kissin, Dmitry M.; Hook, Edward W.; Steinkampf, Michael P.; Bernstein, Kyle T.; Geisler, William M.

doi:10.1097/olq.0000000000001434

Cited by 4 publications

(3 citation statements)

References 29 publications

(73 reference statements)

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“…We found that Pgp3 IgG1 ELISA exhibited superior sensitivity for detecting IgG1 in these women with different CT infection outcomes compared to IgG1 ELISAs using other CT antigens and CT EBs. Over the past 15 years, CT Pgp3 has emerged as the most consistently targeted CT antigen in CT total IgG ELISAs (Wills et al, 2009;Horner et al, 2016;Anyalechi et al, 2022). We confirmed this finding of exceptional immunogenicity in this study by showing 97.5% IgG1 seropositivity in women with CT infection outcomes.…”

Section: Discussionsupporting

confidence: 84%

“…These outcomes included persisting infection versus spontaneous resolution documented at the time of returning for treatment of a positive CT screening test and among those with persisting infection at the time of treatment, the outcome reinfection vs. no reinfection at a 3-month follow-up visit. While IgG antibodies to some of these 9 CT antigens have been previously studied (Tan et al, 2009;Anyalechi et al, 2022;Marques et al, 2022), to our knowledge, this is the first report evaluating IgG1 responses to these antigens and comparing antibody responses to these 9 CT antigens between distinct groups with different CT infection outcomes. We found that Pgp3 IgG1 ELISA exhibited superior sensitivity for detecting IgG1 in these women with different CT infection outcomes compared to IgG1 ELISAs using other CT antigens and CT EBs.…”

Section: Discussionmentioning

confidence: 94%

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Antibody responses to Chlamydia trachomatis vaccine candidate antigens in Chlamydia-infected women and correlation with antibody-mediated phagocytosis of elementary bodies

Yu,

Geisler,

Dai

et al. 2024

Front. Cell. Infect. Microbiol.

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Murine research has revealed a significant role for antibody responses in protection against Chlamydia reinfection. To explore potential humoral immune markers of protection elicited by Chlamydia trachomatis (CT) antigens in humans in the context of presumed clinical correlates of protection, we used both an IgG1-based ELISA and a conventional total IgG ELISA to evaluate antibody responses. We evaluated responses to five CT outer membrane proteins (PmpE, PmpF, PmpG, PmpH, and MOMP), along with other promising CT antigens (Pgp3 and HSP60), negative control antigens (RecO and AtpE), and CT elementary bodies (EBs) in sera from a well-characterized cohort of 60 women with different CT infection outcomes, including two outcomes that are likely clinical correlates of protective immunity: spontaneous resolution of infection and absence of reinfection after treatment. Furthermore, we used a flow cytometry-based assay to measure antibody-mediated phagocytosis by neutrophils in these sera. Results demonstrated that IgG1 ELISA displayed higher sensitivity than conventional total IgG ELISA in assessing antibody responses to CT EBs and antigens. Pgp3 IgG1 ELISA exhibited the highest sensitivity compared to IgG1 ELISA incorporating CT EBs or other antigens, confirming Pgp3 IgG1 ELISA as an ideal assay for CT antibody detection. Most (95%) sera from women with CT infection outcomes exhibited antibody-mediated phagocytosis of CT EBs, which was significantly correlated with IgG1 antibody responses to MOMP, Pgp3, HSP60, and PmpF. However, neither IgG1 responses to CT antigens and EBs nor antibody-mediated phagocytosis were associated with clinical correlates of protection. These findings suggest that neither CT IgG1 antibody detection nor antibody-mediated phagocytosis will be useful as immune correlates of protection against CT infection in humans.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 94%

Antibody responses to Chlamydia trachomatis vaccine candidate antigens in Chlamydia-infected women and correlation with antibody-mediated phagocytosis of elementary bodies

Yu,

Geisler,

Dai

et al. 2024

Front. Cell. Infect. Microbiol.

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“…This is further supported by an earlier study in which we found no difference in CT seropositivity frequency based on CT EB ELISA in Black women enrolled at clinics in 2 US cities (Birmingham and Pittsburgh) with tubal factor infertility versus other infertility etiologies (81% vs. 78%) 14 ; in this same cohort of Black women, another CT antibody assay, a CT Pgp3 ELISA, was also not associated with tubal factor infertility. 15 Thus, CT serological assays that are more specific for CT-associated upper genital tract pathology will be needed for future studies aimed at better understanding the contribution of chlamydia toward reproductive complications in populations of women with high frequency of CT infections.…”

Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis–Specific Antibody Responses in Women in Cameroon With Secondary Infertility

D'Amico,

Mbah,

Gupta

et al. 2023

Sexual Trans Dis

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Chlamydia trachomatis Seroassays Used in Epidemiologic Research: A Narrative Review and Practical Considerations

Waters,

Hybiske,

Ikeda

et al. 2024

The Journal of Infectious Diseases

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Chlamydia trachomatis (CT) is a sexually transmitted infection that can lead to adverse reproductive health outcomes. CT prevalence estimates are primarily derived from screening using nucleic acid amplification tests (NAATs). However, screening guidelines in the United States only include particular subpopulations, and NAATs only detect current infections. In contrast, seroassays identify past CT infections which are important for understanding the public health impacts of CT, including pelvic inflammatory disease and tubal factor infertility. Older seroassays have been plagued by low sensitivity and specificity and have not been validated using a consistent reference measure, making it challenging to compare studies, define the epidemiology of CT and determine the effectiveness of control programs. Newer seroassays have better performance characteristics. This narrative review summarizes the “state of the science” for CT seroassays that have been applied in epidemiologic studies and provides practical considerations for interpreting the literature and employing seroassays in future research.

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Chlamydial Pgp3 Seropositivity and Population-Attributable Fraction Among Women With Tubal Factor Infertility

Abstract: Chlamydia trachomatis Pgp3 seropositivity is associated with tubal factor infertility (TFI) in nonblack women without endometriosis. Past chlamydial infection may account for TFI in 20% of these women.

Cited by 4 publications

References 29 publications

Antibody responses to Chlamydia trachomatis vaccine candidate antigens in Chlamydia-infected women and correlation with antibody-mediated phagocytosis of elementary bodies

Antibody responses to Chlamydia trachomatis vaccine candidate antigens in Chlamydia-infected women and correlation with antibody-mediated phagocytosis of elementary bodies

Chlamydia trachomatis–Specific Antibody Responses in Women in Cameroon With Secondary Infertility

Chlamydia trachomatis Seroassays Used in Epidemiologic Research: A Narrative Review and Practical Considerations

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