An aberrant prostate antigen-specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans
An aberrant prostate antigen-specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans
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DOI：
10.1172/jci38332
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发表时间：
2009-07-01
影响因子：
15.9
通讯作者：
Fong, Lawrence
中科院分区：
文献类型：
--
作者：
Hou, Yafei;DeVoss, Jason;Fong, Lawrence
慢性前列腺炎是一种常见病，病因不明，无特效治疗方法。自身免疫调节因子（Aire）基因表达缺陷的小鼠，其自身抗原的胸腺表达和中枢耐受性缺陷，发展为自发性前列腺炎。在这项研究中，我们发现，Aire缺陷小鼠自发性B和T细胞免疫反应的前列腺自身抗原，精囊分泌蛋白2（SVS2），我们认为这是新的。我们发现，胸腺表达这种自身抗原是依赖于Aire。此外，通过用SVS2免疫在WT小鼠中诱导前列腺炎，证明对SVS2的免疫足以诱导前列腺炎。我们观察到慢性前列腺炎患者具有针对人类SVS2样精囊蛋白精液凝固蛋白的特异性自身抗体，这突出了该抗原的临床相关性。这些结果为自发性慢性前列腺炎是一种自身免疫性疾病，并受中枢和外周耐受调节提供了直接证据。此外，SVS2和semenogelin分别是小鼠和人类中的相关自身抗原。
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.