1153. Alterations in Genital Tract Soluble Mucosal Immune Mediators Associated with Cervical Dysplasia (CIN) May Facilitate HIV Acquisition
Session: Poster Abstract Session: Innate and Adaptive Immunity to Infections
Saturday, October 22, 2011
Room: Poster Hall B1
Background: The greatest need for HIV and STI prevention is in the developing world where women are disproportionately infected by HIV and HPV.  Epidemiological studies suggest that cervicovaginal HPV is associated with an increased risk of HIV aquisition. HPV may modulate the host immune environment to favor its persistence, possibly providing a biological link between HPV and HIV. We hypothesize that women with cervical dysplasia (CIN) will have an altered genital tract mucosal immune environment, which could facilitate HIV infection.

Methods: We conducted a pilot study comparing soluble immune mediators and endogenous antimicrobial activity in genital tract secretions collected by cervicovaginal lavage (CVL) in a cohort of HIV-negative women with CIN-1 (n=12), CIN-3 (n=37), or PAP negative controls (n=57).  CVL were clarified by centrifugation and supernatants evaluated for concentrations of cytokines, chemokines, antimicrobial peptides and total protein and endogenous anti-E. coli activity, a potential biomarker of intact mucosal host defense.  Only CIN with the most important high-risk (HR) HPV types (16, 18, 31, 45, and/or 52) were chosen for study.  HPV typing was performed by PCR on cell pellets using MY09/MY11 primers.

Results: Women with CIN-1 and CIN-3 displayed significantly higher levels of pro-inflammatory cytokines and chemokines including IL-1α, IL-1β, and IL-8 (p<0.01) compared to controls.  Women with CIN-3 also had higher levels of RANTES (p<0.01).  Conversely, women with CIN-1 and CIN-3 displayed significantly lower levels of anti-inflammatory mediators including IL-1 receptor antagonist and secretory leukocyte inhibitor (p<0.01) and lower levels of protective immune mediators such as human beta defensins 2 and 3 (p< 0.02). Women with CIN-3 also had the lowest endogenous anti-E. coli activity (p<0.02).

Conclusion: This first comprehensive study of mucosal immune mediators in the genital tract indicates that HR-HPV infected CIN is associated with an increase in inflammatory and loss in protective immune mediators. These changes are consistent with the mucosal environment described in women who seroconvert to HIV and suggest a mechanism whereby persistent HPV may contribute to an increased risk of HIV acquisition.


Subject Category: E. Innate and adaptive immunity to infections, including vaccine immunology

Mohak Mhatre, M.D.1, Thomas McAndrew1, Colleen Carpenter, BA1, Robert Burk, MD2, Mark Einstein, MD, MS1 and Betsy C. Herold, MD, FIDSA1, (1)Albert Einstein College of Medicine, Bronx, NY, (2)Pediatrics, Albert Einstein College of Medicine, Bronx, NY

Disclosures:

M. Mhatre, None

T. McAndrew, None

C. Carpenter, None

R. Burk, None

M. Einstein, None

B. C. Herold, None

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