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Foreskin Langerhans' Cell Density of HIV Infected and Uninfected Men in Rakai, Uganda
Kristine Johnson*1, J Taube1, R Sharma1, A Rabkin2, D Serwadda3, G Kigozi3, S Watya3, M Wawer3,4, R Gray3,4, and T Quinn1,5
1Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 2Stanford Univ, Palo Alto, CA, US; 3Rakai Hlth Sci Prgm, Kalisizo, Uganda; 4Johns Hopkins Univ Bloomberg Sch of Publ Hlth, Baltimore, MD, US; and 5NIAID, NIH, Bethesda, MD, US
Background: The efficacy of circumcision to prevent
HIV infection has been demonstrated in three recent clinical trials. While it
has been hypothesized that foreskin removal leads to protection by removing HIV
target cells, including Langerhans' cells (LC), there is reason to suspect that
the foreskin may play a role in transmission. The foreskins from the
circumcision trial in Uganda present a unique opportunity to study the foreskin
immunologic milieu. We hypothesized that HIV+ men have lower baseline CD1a+
dendritic cell density in the foreskin epithelium compared to their HIV- peers.
Methods: Men from two trials of male circumcision in
Rakai, Uganda were selected by HIV status and availability of foreskin
tissue. Specimens were fixed in ethanol postoperatively. After inspection for
identification of any gross lesions, three full-thickness sections were
collected and paraffin-embedded and routine histology was performed.
Langerhans' cells (LC) were identified using immunohistochemistry (IHC) performed
on a Bond autostainer with a monoclonal anti-CD1a+ antibody. IHC slides were
scanned at 200x final magnification using a ScanScope slide scanner (Aperio
Technologies, Vista, CA) and imported into ImageScope software (version 8.0,
Aperio), where grids of a known area were superimposed. CD1a+ LCs in the
epidermis were manually counted. Three to six fields were counted per
subject. Densities were recorded as number cells/μm 2. Median densities
were compared according to HIV status using the Wilcoxon rank-sum test. The
Kruskal-Wallis test was used to evaluate density by sexual behavior and exam
findings.
Results: Of men selected, median age was 30.5 years
(IQR 25–37). 20 were HIV+ and 16 HIV-, of median age 35 (IQR 30–41.5) and 24.5
(20.5-29.5), respectively. The median CD1a+ LC density was 0.241 (IQR,
0.197-0.294). The median CD1a+ LC density was 0.256 (IQR 0.199-0.298) and
0.240 (0.167-0.282), among HIV- and HIV+ subjects, respectively. Median
density did not vary by age (p=0.48), HIV status (p=0.41), or number of sex
partners in the last year (p=0.11).
Conclusions: In this preliminary analysis, foreskin
LC density is not influenced by HIV status. Improved understanding of the
foreskin immune milieu will inform proposed mechanisms of protection (or risk)
associated with circumcision in HIV- and HIV+ men, respectively.
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