title: Higher prevalence of colonization with Gardnerella vaginalis and gram-negative anaerobes in patients with recurrent miscarriage and elevated peripheral natural killer cells.
abstract: The role of vaginal infections in recurrent miscarriage (RM) is discussed controversially and screening is not recommended in international guidelines. Peripheral and uterine NK cells (pNK, uNK) play an important role in the establishment of a healthy pregnancy and are targets of immune diagnostics in RM patients. The aim of this study was to analyze the composition of the vaginal microbiota in RM patients and to correlate the findings to clinical characteristics as well as NK cell parameters. In total, n=243 RM patients with ≥3 consecutive miscarriages were recruited between 11/2011 and 03/2016. Vaginal swabs were analyzed by microbiological culture. Further, a cervical swab was taken in n=187 patients and the presence of Chlamydia trachomatis was evaluated by a molecular assay. Peripheral blood levels of CD45+CD3-CD56+CD16+ pNK (determined by four-color fluorescence flow cytometry) and CD56+ uNK (uterine biopsy, determined by immunohistochemistry) were analyzed. The prevalence of Gardnerella vaginalis colonization in RM patients was 19.0%, gram-negative anaerobes 20.5%, Candida species 7.9%, group B Streptococcus 11.0% and Enterobacteriaceae 14.8%. Commensal lactobacilli were absent in 14.5% of the women. Chlamydia trachomatis was detected in n=1 case (0.53%). The prevalence of Gardnerella vaginalis and gram-negative anaerobes in RM patients with elevated pNK (>280/μl, n=69) was significantly higher (p=0.012, p=0.04) compared to patients with normal pNK (n=174). In conclusion, RM patients with elevated pNK suffer more often from colonization by Gardnerella vaginalis and gram-negative anaerobes. This might indicate an association between the vaginal microbiota, local inflammation, changes in immune parameters and miscarriage.
authors.affiliation: Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
authors.forename: R J
authors.initials: RJ
authors.lastname: Kuon
authors.affiliation: Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Togawa
authors.affiliation: Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Vomstein
authors.affiliation: Placenta-Lab, Department of Obstetrics, University Hospital Jena, Am Klinikum 1, 07747 Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Weber
authors.affiliation: Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Goeggl
authors.affiliation: Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Strowitzki
authors.affiliation: Placenta-Lab, Department of Obstetrics, University Hospital Jena, Am Klinikum 1, 07747 Jena, Germany.
authors.forename: U R
authors.initials: UR
authors.lastname: Markert
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Zimmermann
authors.affiliation: Transplantation-Immunology, Institute of Immunology, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 672, 69120 Heidelberg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Daniel
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
authors.forename: A H
authors.initials: AH
authors.lastname: Dalpke
authors.affiliation: Department of Gynecological Endocrinology and Reproductive Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: bettina.toth@i-med.ac.at.
authors.forename: B
authors.initials: B
authors.lastname: Toth
mesh_terms: D000026:Abortion, Habitual / Q000453:epidemiology* / Q000276:immunology; D000328:Adult; D019002:CD56 Antigen / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D006194:Gardnerella vaginalis / Q000502:physiology*; D016908:Gram-Positive Bacterial Infections / Q000453:epidemiology* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000473:pathology*; D008297:Male; D011247:Pregnancy; D015995:Prevalence; D017452:Receptors, IgG / Q000378:metabolism; D014621:Vagina / Q000276:immunology / Q000382:microbiology*; D016585:Vaginosis, Bacterial / Q000453:epidemiology* / Q000276:immunology
chemical_list: D019002:CD56 Antigen; D017452:Receptors, IgG
keywords: Gardnerella vaginalis; Natural killer cells; Recurrent miscarriage; Vaginal microbiota