An aberrant prostate antigen-specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans.
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.
Hou
Yafei
Y
Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California 94143, USA.
DeVoss
Jason
J
Dao
Vinh
V
Kwek
Serena
S
Simko
Jeffrey P
JP
McNeel
Douglas G
DG
Anderson
Mark S
MS
Fong
Lawrence
L
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002908:Chronic Disease; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011467:Prostate / Q000473:pathology; D011472:Prostatitis / Q000209:etiology*; D029607:Seminal Vesicle Secretory Proteins / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology; D000096927:AIRE Protein
D001323:Autoantibodies; D029607:Seminal Vesicle Secretory Proteins; D014157:Transcription Factors; D000096927:AIRE Protein; C520624:SVS2 protein, mouse; C424482:seminal vesicle-specific antigen