Immunometabolic profiling of cervicovaginal lavages identifies key signatures associated with adenomyosis
Georgia M. Lorentzen,
Paweł Łaniewski,
Haiyan Cui,
Denise J. Roe,
Jamal Mourad,
Nichole D. Mahnert,
Leslie V. Farland,
Melissa M. Herbst-Kralovetz
Affiliations
Georgia M. Lorentzen
Department of Obstetrics and Gynaecology, College of Medicine – Phoenix, University of Arizona, Phoenix, AZ 85004, USA; Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
Paweł Łaniewski
Department of Basic Medical Sciences, College of Medicine – Phoenix, University of Arizona, Phoenix, AZ 85004, USA
Haiyan Cui
UA Cancer Center, University of Arizona, Tucson, AZ 85719, USA
Denise J. Roe
UA Cancer Center, University of Arizona, Tucson, AZ 85719, USA; Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ 85724, USA
Jamal Mourad
Department of Obstetrics and Gynaecology, College of Medicine – Phoenix, University of Arizona, Phoenix, AZ 85004, USA; Department of Obstetrics and Gynaecology, Banner-University Medical Center Phoenix, Phoenix, AZ 85006, USA
Nichole D. Mahnert
Department of Obstetrics and Gynaecology, College of Medicine – Phoenix, University of Arizona, Phoenix, AZ 85004, USA; Department of Obstetrics and Gynaecology, Banner-University Medical Center Phoenix, Phoenix, AZ 85006, USA
Leslie V. Farland
Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ 85724, USA; Department of Obstetrics and Gynaecology, University of Arizona, College of Medicine Tucson, Tucson, AZ 85724, USA
Melissa M. Herbst-Kralovetz
Department of Obstetrics and Gynaecology, College of Medicine – Phoenix, University of Arizona, Phoenix, AZ 85004, USA; Department of Basic Medical Sciences, College of Medicine – Phoenix, University of Arizona, Phoenix, AZ 85004, USA; UA Cancer Center, University of Arizona, Tucson, AZ 85719, USA; Corresponding author
Summary: Adenomyosis is a burdensome gynecologic condition that is associated with pelvic pain, dysmenorrhea, and abnormal uterine bleeding, leading to a negative impact on quality of life; and yet is often left undiagnosed. We recruited 108 women undergoing hysterectomy for benign gynecologic conditions and collected non-invasive cervicovaginal lavage samples for immunometabolic profiling. Patients were grouped according to adenomyosis status. We investigated the levels of 72 soluble immune proteins and >900 metabolites using multiplex immunoassays and an untargeted global metabolomics platform. There were statistically significant alterations in the levels of several immune proteins and a large quantity of metabolites, particularly cytokines related to type II immunity and amino acids, respectively. Enrichment analysis revealed that pyrimidine metabolism, carnitine synthesis, and histidine/histamine metabolism were significantly upregulated pathways in adenomyosis. This study demonstrates utility of non-invasive sampling combined with immunometabolic profiling for adenomyosis detection and a greater pathophysiological understanding of this enigmatic condition.
