molBV reveals immune landscape of bacterial vaginosis and predicts human papillomavirus infection natural history.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 01 2022
11 01 2022
Historique:
received:
11
06
2021
accepted:
30
11
2021
entrez:
12
1
2022
pubmed:
13
1
2022
medline:
11
2
2022
Statut:
epublish
Résumé
Bacterial vaginosis (BV) is a highly prevalent condition that is associated with adverse health outcomes. It has been proposed that BV's role as a pathogenic condition is mediated via bacteria-induced inflammation. However, the complex interplay between vaginal microbes and host immune factors has yet to be clearly elucidated. Here, we develop molBV, a 16 S rRNA gene amplicon-based classification pipeline that generates a molecular score and diagnoses BV with the same accuracy as the current gold standard method (i.e., Nugent score). Using 3 confirmatory cohorts we show that molBV is independent of the 16 S rRNA region and generalizable across populations. We use the score in a cohort without clinical BV states, but with measures of HPV infection history and immune markers, to reveal that BV-associated increases in the IL-1β/IP-10 cytokine ratio directly predicts clearance of incident high-risk HPV infection (HR = 1.86, 95% CI: 1.19-2.9). Furthermore, we identify an alternate inflammatory BV signature characterized by elevated TNF-α/MIP-1β ratio that is prospectively associated with progression of incident infections to CIN2 + (OR = 2.81, 95% CI: 1.62-5.42). Thus, BV is a heterogeneous condition that activates different arms of the immune response, which in turn are independent risk factors for HR-HPV clearance and progression. Clinical Trial registration number: The CVT trial has been registered under: NCT00128661.
Identifiants
pubmed: 35017496
doi: 10.1038/s41467-021-27628-3
pii: 10.1038/s41467-021-27628-3
pmc: PMC8752746
doi:
Substances chimiques
Cytokines
0
IL1B protein, human
0
Interleukin-1beta
0
Banques de données
ClinicalTrials.gov
['NCT00128661']
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
233Subventions
Organisme : NIAID NIH HHS
ID : R56 AI072204
Pays : United States
Organisme : NCI NIH HHS
ID : N01CP11005
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA078527
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI072204
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013330
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA078527
Pays : United States
Investigateurs
Bernal Cortés
(B)
Paula González
(P)
Silvia E Jiménez
(SE)
Ana Cecilia Rodríguez
(AC)
Allan Hildesheim
(A)
Aimée R Kreimer
(AR)
Douglas R Lowy
(DR)
Mark Schiffman
(M)
John T Schiller
(JT)
Mark Sherman
(M)
Sholom Wacholder
(S)
Troy J Kemp
(TJ)
Mary K Sidawy
(MK)
Wim Quint
(W)
Leen-Jan van Doorn
(LJ)
Linda Struijk
(L)
Joel M Palefsky
(JM)
Teresa M Darragh
(TM)
Mark H Stoler
(MH)
Informations de copyright
© 2022. The Author(s).
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