10.6084/M9.FIGSHARE.C.6232595.V1
Sean M. Hughes
Sean M.
Hughes
University of Washington
Claire N. Levy
Claire N.
Levy
University of Washington
Ronit Katz
Ronit
Katz
University of Washington
Erica M. Lokken
Erica M.
Lokken
University of Washington
Melis N. Anahtar
Melis N.
Anahtar
Massachusetts General Hospital
Melissa Barousse Hall
Melissa Barousse
Hall
University of Louisville
Frideborg Bradley
Frideborg
Bradley
Karolinska University Hospital
Philip E. Castle
Philip E.
Castle
National Cancer Institute
Valerie Cortez
Valerie
Cortez
University of California, Santa Cruz
Gustavo F. Doncel
Gustavo F.
Doncel
Eastern Virginia Medical School
Raina Fichorova
Raina
Fichorova
Harvard University
Paul L. Fidel
Paul L.
Fidel
Louisiana State University Health Sciences Center New Orleans
Keith R. Fowke
Keith R.
Fowke
University of Manitoba
Suzanna C. Francis
Suzanna C.
Francis
London School of Hygiene & Tropical Medicine
Mimi Ghosh
Mimi
Ghosh
George Washington University
Loris Y. Hwang
Loris Y.
Hwang
University of California, Los Angeles
Mariel Jais
Mariel
Jais
George Washington University
Vicky Jespers
Vicky
Jespers
Institute of Tropical Medicine Antwerp
Vineet Joag
Vineet
Joag
University of Minnesota
Rupert Kaul
Rupert
Kaul
University of Toronto
Jordan Kyongo
Jordan
Kyongo
Institute of Tropical Medicine Antwerp
Timothy Lahey
Timothy
Lahey
University of Vermont
Huiying Li
Huiying
Li
University of California, Los Angeles
Julia Makinde
Julia
Makinde
International AIDS Vaccine Initiative
Imperial College London
Lyle R. McKinnon
Lyle R.
McKinnon
University of Nairobi
University of Manitoba
Centre for the AIDS Programme of Research in South Africa
Anna-Barbara Moscicki
Anna-Barbara
Moscicki
University of California, Los Angeles
Richard M. Novak
Richard M.
Novak
University of Illinois at Chicago
Mickey V. Patel
Mickey V.
Patel
Dartmouth College
Intira Sriprasert
Intira
Sriprasert
University of Southern California
Andrea R. Thurman
Andrea R.
Thurman
Eastern Virginia Medical School
Sergey Yegorov
Sergey
Yegorov
McMaster University
Nelly Rwamba Mugo
Nelly Rwamba
Mugo
Kenya Medical Research Institute
University of Washington
Alison C. Roxby
Alison C.
Roxby
Fred Hutchinson Cancer Center
University of Washington
Elizabeth Micks
Elizabeth
Micks
University of Washington
Florian Hladik
Florian
Hladik
0000-0002-0375-2764
Fred Hutchinson Cancer Center
University of Washington
Changes in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data
Abstract Background Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence. Methods We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples. Results We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here. Conclusions Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.
Immunology
figshare
2022
2022-10-05
2022-10-05
Collection
10.6084/m9.figshare.c.6232595
CC BY 4.0