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Association of a variable number tandem repeat in the NLRP3 gene in women with susceptibility to RVVC

Authors
  • Jaeger, M.1
  • Carvalho, A.2
  • Cunha, C.2
  • Plantinga, T. S.1
  • van de Veerdonk, F.1
  • Puccetti, M.2
  • Galosi, C.2
  • Joosten, L. A. B.1
  • Dupont, B.3
  • Kullberg, B. J.1
  • Sobel, J. D.4
  • Romani, L.2
  • Netea, M. G.1
  • 1 Radboud University Medical Center, Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Nijmegen, 6500 HB, The Netherlands , Nijmegen (Netherlands)
  • 2 University of Perugia, Polo Unico Sant’Andrea delle Fratte, Department of Experimental Medicine, Perugia, 06132, Italy , Perugia (Italy)
  • 3 Hôpital Necker, Paris, France , Paris (France)
  • 4 Wayne State University School of Medicine, Department of Medicine, Infectious Diseases, Detroit, MI, USA , Detroit (United States)
Type
Published Article
Journal
European Journal of Clinical Microbiology & Infectious Diseases
Publisher
Springer-Verlag
Publication Date
Mar 07, 2016
Volume
35
Issue
5
Pages
797–801
Identifiers
DOI: 10.1007/s10096-016-2600-5
Source
Springer Nature
Keywords
License
Green

Abstract

Vaginal infections with Candida spp. frequently occur in women of childbearing age. A small proportion of these women experience recurrent vulvovaginal candidosis (RVVC), which is characterized by at least three episodes of infection in one year. In addition to known risk factors such as antibiotics, diabetes, or pregnancy, host genetic variation and inflammatory pathways such as the IL-1/Th17 axis have been reported to play a substantial role in the pathogenesis of RVVC. In this study, we assessed a variable number tandem repeat (VNTR) polymorphism in the NLRP3 gene that encodes a component of the inflammasome, processing the proinflammatory cytokines IL-1β and IL-18. A total of 270 RVVC patients and 583 healthy controls were analyzed, and increased diseases susceptibility was associated with the presence of the 12/9 genotype. Furthermore, functional studies demonstrate that IL-1β production at the vaginal surface is higher in RVVC patients bearing the 12/9 genotype compared to controls, whereas IL-1Ra levels were decreased and IL-18 levels remained unchanged. These findings suggest that IL-1β-mediated hyperinflammation conveyed by the NLRP3 gene plays a causal role in the pathogenesis of RVVC and may identify this pathway as a potential therapeutic target in the disease.

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