title: Elevated elafin/trappin-2 in the female genital tract is associated with protection against HIV acquisition.
abstract: OBJECTIVE
  Globally, heterosexual intercourse is the primary route of HIV-1 (HIV) transmission. It follows that mechanisms that protect against HIV infection are likely operative at the genital mucosa. In HIV-resistant Kenyan sex workers who are highly exposed to HIV infection yet remain uninfected, protection correlates with HIV-specific immune responses and genetic factors. However, these factors do not entirely explain this model of natural immunity to HIV. We hypothesized that protection may be mediated by innate immune proteins in the genital tract of HIV-resistant sex workers.
  
  
  METHODS
  The genital proteome of mucosal secretions from HIV-resistant women was examined using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Cervical lavage samples were collected from 315 HIV-resistant, HIV-uninfected and HIV-infected commercial sex workers.
  
  
  RESULTS
  Univariate analysis identified a 6 kDa biomarker of HIV resistance in genital secretions from these women. This protein was identified by tandem mass spectrometry as elafin and was found to be overexpressed in HIV-resistant women compared with HIV-uninfected (P = 0.001) and infected (P = 0.002) women. The elevated levels of elafin/trappin-2 in HIV-resistant women were confirmed using ELISA. The prospective association of elevated cervicovaginal elafin/trappin-2 levels with protection from HIV acquisition was then confirmed in an independent cohort of high-risk female sex workers.
  
  
  CONCLUSIONS
  Using a unique proteomics approach in a large scale, cross-sectional cohort study, we identified elafin/trappin-2 as a novel innate immune factor, which is highly associated with resistance. This association was confirmed within an independent, prospective cohort study. Genital tract elafin/trappin-2 levels constitute a natural correlate of HIV protection in humans.
authors: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada. shehzad.iqbal@utoronto.ca
authors: Shehzad M
authors: SM
authors: Iqbal
authors: Terry B
authors: TB
authors: Ball
authors: Pauline
authors: P
authors: Levinson
authors: Lillian
authors: L
authors: Maranan
authors: Walter
authors: W
authors: Jaoko
authors: Charles
authors: C
authors: Wachihi
authors: Brian J
authors: BJ
authors: Pak
authors: Vladimir N
authors: VN
authors: Podust
authors: Kristina
authors: K
authors: Broliden
authors: Taha
authors: T
authors: Hirbod
authors: Rupert
authors: R
authors: Kaul
authors: Francis A
authors: FA
authors: Plummer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D015986:Confounding Factors, Epidemiologic; D053492:Elafin / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D005836:Genitalia, Female / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D011446:Prospective Studies; D011477:Sex Work; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D015415:Biomarkers; D053492:Elafin; C506806:PI3 protein, human