Identification and preliminary study of immunogens involved in autoimmune prostatitis in human males.

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.