In men at risk of HIV infection, IgM, IgG1, IgG3, and IgA reach the human foreskin epidermis.
We profiled the humoral response in the penis, an area that has been minimally explored but may be relevant for protecting insertive men against HIV and other sexually acquired infections. Comparing paired tissue samples from 20 men at risk of HIV infection, foreskin contains less immunoglobulin A (IgA) and more IgG2 than colon. Using foreskin dermal and epidermal explants and paired plasma from 17 men, we examined Ig accumulation by normalizing Ig to human serum albumin (HSA) transudation. Dermal IgM, IgG2, IgA, and IgE ratios were greater than that in plasma, suggesting there is local antibody secretion at the dermis. Local Ig transcription was concentrated at the inner rather than the outer foreskin, and inner foreskin Ig ratios did not correlate with blood, indicating that localized production can contribute to the foreskin response. IgM, IgG1, IgG3, and IgA have preferential access to the foreskin epidermis, whereas IgG2, IgG4, and IgE are restricted to the dermis. Lastly, Ad5-specific IgA was selectively present in the colon, whereas foreskin Ad5 IgG was mainly derived from blood, and reached the inner epidermis at higher ratios than the outer (P<0.002). In summary, the foreskin antibody response combines local and systemic sources, and there is selective isotype accumulation in the epidermis.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
M P
MP
Lemos
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
S T
ST
Karuna
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
G J
GJ
Mize
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Y
Y
Fong
US Naval Medical Research Unit 6 (NAMRU-6), Lima, Perú
S M
SM
Montano
Asociación Civil Impacta Salud y Educación, Lima, Perú
C
C
Ganoza
Asociación Civil Impacta Salud y Educación, Lima, Perú
J R
JR
Lama
Asociación Civil Impacta Salud y Educación, Lima, Perú
J
J
Sanchez
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle Washington, USA.|Department of Laboratory Medicine, University of Washington, Seattle Washington, USA.|Department of Global Health, University of Washington, Seattle Washington, USA.
M J
MJ
McElrath
D000256:Adenoviridae / Q000276:immunology*; D000328:Adult; D002478:Cells, Cultured; D003106:Colon / Q000276:immunology; D004817:Epidermis / Q000276:immunology*; D052816:Foreskin / Q000276:immunology*; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008297:Male; D009500:Neutralization Tests
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M