Lu Jin-Chun, Shen Jia-Ming, Hu Xue-Chun, Peng Long-Ping, Hong Zhi-Wei, Yao Bing
The Reproductive Medical Center, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China.
Department of Laboratory Science, Nanjing Hospital, Jiangsu Corps, The Armed Police Force, PLA, Nanjing, Jiangsu, China.
Prostate. 2018 Jun 26. doi: 10.1002/pros.23684.
Experimental models have confirmed that autoimmunity is an important factor in the onset of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, there is no conclusive evidence on whether autoimmune prostatitis exists in human males.
Rabbits were immunized with either human prostate tissue homogenates or normal saline and the antiserum was collected. Two-dimensional electrophoresis (2-DE) was performed on the homogenates and Western blotting was conducted on the sera. The identified human prostate tissue immunodominant antigens (HPTIAs) were detected by mass spectrometry. The serum immunoglobulin (Ig)G from the immunized rabbits was purified with protein A-agarose, and the purified IgG was linked with Sepharose to purify HPTIAs by affinity chromatography. Non-obese diabetic (NOD) mice were immunized with the purified HPTIAs, and the levels of serum antibodies, INF-γ, and histopathological changes in their prostate tissues were detected. The purified HPTIAs were coated into polystyrene pores and serum autoantibodies in CP/CPPS patients were detected by enzyme-linked immunosorbent assay (ELISA). Meanwhile, serum interleukin 2 (IL-2), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNFα) levels in CP/CPPS patients were also determined by ELISA.
Sixteen HPTIAs were identified. Among them, three types were reported to be associated with prostatic diseases. Prostatitis was induced in mice immunized with the 16-HPTIA complex, with positive serum autoantibody and increased prostatic IFN-γ levels. The positive rate of serum autoantibodies against HPTIAs was significantly higher in CP/CPPS patients (23.1%, 18/78) than in the control (2.7%, 2/75). But there was no significant difference in serum TNFα, IFNγ, and IL-2 levels between the CPPS patients with positive and negative autoantibodies against HPTIAs.
Autoantibodies against HPTIAs exist in part in CP/CPPS patients, which implies that autoimmunity and the 16 HPTIAs are important factors in the onset of CP/CPPS. The detection of serum autoantibodies could be applied in clinical diagnoses of autoimmune prostatitis; treatment protocols might change. Additional studies are needed to determine which of the 16 HPTIAs is the most important.
实验模型已证实自身免疫是慢性前列腺炎/慢性盆腔疼痛综合征（CP/CPPS）发病的重要因素；然而，关于男性体内是否存在自身免疫性前列腺炎尚无确凿证据。
用人类前列腺组织匀浆或生理盐水免疫兔子并收集抗血清。对匀浆进行二维电泳（2-DE），对血清进行蛋白质印迹分析。通过质谱检测鉴定出的人类前列腺组织免疫显性抗原（HPTIA）。用蛋白A-琼脂糖纯化免疫兔子的血清免疫球蛋白（Ig）G，将纯化的IgG与琼脂糖凝胶连接，通过亲和层析纯化HPTIA。用纯化的HPTIA免疫非肥胖糖尿病（NOD）小鼠，检测其血清抗体水平、INF-γ水平以及前列腺组织的组织病理学变化。将纯化的HPTIA包被到聚苯乙烯孔中，通过酶联免疫吸附测定（ELISA）检测CP/CPPS患者血清中的自身抗体。同时，也通过ELISA测定CP/CPPS患者血清白细胞介素2（IL-2）、干扰素γ（IFNγ）和肿瘤坏死因子α（TNFα）水平。
鉴定出16种HPTIA。其中，有3种类型据报道与前列腺疾病有关。用16-HPTIA复合物免疫的小鼠诱发了前列腺炎，血清自身抗体呈阳性，前列腺IFN-γ水平升高。CP/CPPS患者血清中针对HPTIA的自身抗体阳性率（23.1%，18/78）显著高于对照组（2.7%，2/75）。但针对HPTIA自身抗体阳性和阴性的CPPS患者血清TNFα、IFNγ和IL-2水平无显著差异。
CP/CPPS患者体内部分存在针对HPTIA的自身抗体，这意味着自身免疫和这16种HPTIA是CP/CPPS发病的重要因素。血清自身抗体检测可应用于自身免疫性前列腺炎的临床诊断；治疗方案可能会改变。需要进一步研究以确定这16种HPTIA中哪一种最为重要。
