An aberrant prostate antigen–specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans
Yafei Hou, … , Mark S. Anderson, Lawrence Fong
Yafei Hou, … , Mark S. Anderson, Lawrence Fong
Published June 1, 2009
Citation Information: J Clin Invest. 2009;119(7):2031-2041. https://doi.org/10.1172/JCI38332.
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Research Article Immunology

An aberrant prostate antigen–specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans

Abstract

Chronic prostatitis is a common disease of unclear etiology and has no specific treatment. Mice deficient in the expression of the autoimmune regulator (Aire) gene, which are defective in thymic expression of self antigens and central tolerance, develop spontaneous prostatitis. In this study, we found that Aire-deficient mice developed spontaneous B and T cell immune responses to a prostate autoantigen, seminal vesicle secretory protein 2 (SVS2), which we believe to be novel. We show that thymic expression of this self antigen was Aire dependent. Moreover, prostatitis was induced in WT mice through immunization with SVS2, demonstrating that immunity to SVS2 was sufficient to induce prostatitis. The clinical relevance of this antigen was highlighted by our observation that patients with chronic prostatitis possessed specific autoantibodies against the human SVS2-like seminal vesicle protein semenogelin. These results provide direct evidence that spontaneous chronic prostatitis is an autoimmune disease and is regulated by both central and peripheral tolerance. Moreover, SVS2 and semenogelin are among the relevant autoantigens in mice and humans, respectively.

Authors

Yafei Hou, Jason DeVoss, Vinh Dao, Serena Kwek, Jeffrey P. Simko, Douglas G. McNeel, Mark S. Anderson, Lawrence Fong

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Figure 6

Induction of SVS2-specific antibody and T cell response by immunizing WT B6 mice with MBP-SVS2.

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Induction of SVS2-specific antibody and T cell response by immunizing WT...
(A and B) WT B6 mice were immunized with either (A) MBP-SVS2 or (B) MBP emulsified in CFA. Sera from individual immunized B6 mice were used to immunoblot semen-purified SVS2 or OVA. Each blot represents an individual animal. For each experiment, shown is 1 group of 4 mice, representative of 14 total mice immunized. (C) The pooled splenocytes from 4 mice that were immunized with MBP-SVS2 or MBP were assessed by IFN-γ ELISPOT for reactivity to purified SVS2 (10 μg/ml), OVA (10 μg/ml), or PBS. Splenocytes depleted of CD8+ or CD4+ T cells were also assessed. Values are mean ± SD. Results are representative of 2 experiments.