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J Immunol. 2018 Apr 15;200(8):2941-2956. doi: 10.4049/jimmunol.1701658. Epub 2018 Mar 12.

Discovery of Blood Transcriptional Endotypes in Women with Pelvic Inflammatory Disease.

Author information

1
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
2
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
3
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; and.
4
Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
5
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; toni.darville@unc.edu.

Abstract

Sexually transmitted infections with Chlamydia trachomatis and/or Neisseria gonorrhoeae and rates of pelvic inflammatory disease (PID) in women continue to rise, with reinfection being common because of poor adaptive immunity. Diagnosis remains imprecise, and pathogenesis data are derived primarily from monoinfection of mice with C. trachomatis or N. gonorrhoeae By comparing blood mRNA responses of women with C. trachomatis- and/or N. gonorrhoeae-induced PID and histologic endometritis with those from women with C. trachomatis and/or N. gonorrhoeae infection limited to their cervix and asymptomatic uninfected women determined via microarray, we discovered important pathogenic mechanisms in PID and response differences that provide a pathway to biomarker discovery. Women with N. gonorrhoeae- and/or C. trachomatis-induced PID exhibit overexpression of myeloid cell genes and suppression of protein synthesis, mitochondrial oxidative phosphorylation, and T cell-specific genes. Coinfected women exhibited the greatest activation of cell death pathways and suppression of responses essential for adaptive immunity. Women solely infected with C. trachomatis expressed elevated levels of type I and type II IFN genes, and enhanced type I IFN-induced chemokines in cervical secretions were associated with ascension of C. trachomatis to the endometrium. Blood microarrays reveal discrete pathobiological endotypes in women with PID that are driven by pathogen invasion of the upper genital tract.

PMID:
29531169
PMCID:
PMC5893373
DOI:
10.4049/jimmunol.1701658
[Indexed for MEDLINE]
Free PMC Article

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