TY - GEN A1 - Liedtke, Victoria A1 - Stöckle, Michael A1 - Junker, Kerstin A1 - Roggenbuck, Dirk T1 - Benign prostatic hyperplasia - a novel autoimmune disease with a potential therapy consequence? T2 - Autoimmunity Reviews N2 - Benign prostatic hyperplasia (BPH) is considered as an age-related disease of men with an unknown etiopathophysiology. Chronic inflammation has been proposed as one of the major pathophysiological mechanisms. There is growing evidence for the involvement of autoimmune responses in an inflammatory setting in the prostate. Patients with autoimmune diseases show a significantly elevated prevalence of BPH. Conventional therapy options for BPH are limited, rendering surgery the ultimate alternative. However, immunosuppression via tumor necrosis factor alpha blocker appears to reduce symptoms in patients with BPH and concurrent autoimmune disease due to the reduction of epithelial hyperplasia and macrophage-induced inflammation. New diagnostic options using HEp-2 cells with overexpression of LEDGF/p75 or mitochondrial DNA as autoimmune targets could be used to identify BPH patients with autoimmune responses. Given the presumed involvement of autoimmune responses in BPH and the efficacy of immunosuppression in reducing BPH symptoms, BPH or subvariants of BPH may be candidates for a new autoimmune disease in males. KW - Autoimmunity Benign prostatic hyperplasia Anti-mitochondrial DNA antibodies LEDGF/p75 Y1 - 2024 U6 - https://doi.org/10.1016/j.autrev.2023.103511 SN - 1568-9972 VL - 23 IS - 3 PB - Elsevier BV ER - TY - GEN A1 - Liedtke, Victoria A1 - Rose, Laura A1 - Hiemann, Rico A1 - Nasser, Abdullah A1 - Rödiger, Stefan A1 - Bonaventura, Alena A1 - Winkler, Laura A1 - Sowa, Mandy A1 - Stöckle, Michael A1 - Schierack, Peter A1 - Junker, Kerstin A1 - Roggenbuck, Dirk T1 - Over-Expression of LEDGF/p75 in HEp-2 Cells Enhances Autoimmune IgG Response in Patients with Benign Prostatic Hyperplasia—A Novel Diagnostic Approach with Therapeutic Consequence? T2 - International Journal of Molecular Sciences N2 - Lens epithelium-derived growth factor splice variant of 75 kDa (LEDGF/p75) is an autoantigen over-expressed in solid tumors and acts as a stress-related transcriptional co-activator. Participation of autoimmune responses in the pathophysiology of benign prostatic hyperplasia (PBH) and a corresponding immunosuppressive therapy by TNFalpha antagonists has been recently suggested. Thus, autoAb testing could aid in the diagnosis of BPH patients profiting from such therapy. We generated CRISPR/Cas9 modified HEp-2 LEDGF knock-out (KO) and HEp-2 LEDGF/p75 over-expressing (OE) cells and examined IgG autoantibody reactivity to LEDGF/p75 in patients with prostate cancer (PCa, n = 89), bladder cancer (BCa, n = 116), benign prostatic hyperplasia (BPH, n = 103), and blood donors (BD, n = 60) by indirect immunofluorescence assay (IFA). Surprisingly, we could not detect elevated binding of autoAbs against LEDGF/p75 in cancer patients, but autoAb reactivity to LEDGF/p75 OE cells in about 50% of patients with BPH was unexpectedly significantly increased. Furthermore, a line immunoassay enabling the detection of 18 different autoAbs revealed a significantly increased occurrence of anti-dsDNA autoAbs in 34% of BPH patients in contrast to tumor patients and BD. This finding was confirmed by anti-mitochondrial (mDNA) autoAb detection with the Crithidia luciliae immunofluorescence test, which also showed a significantly higher prevalence (34%) of anti-mDNA autoAbs in BPH. In summary, our study provided further evidence for the occurrence of autoimmune responses in BPH. Furthermore, LEDGF/p75 over-expression renders HEp-2 cells more autoantigenic and an ideal target for autoAb analysis in BPH with a potential therapy consequence. KW - LEDGF/p75 KW - autoimmunity KW - CRISPR/Cas9 KW - dsDNA KW - mDNA Y1 - 2023 U6 - https://doi.org/10.3390/ijms24076166 SN - 1422-0067 VL - 24 IS - 7 ER -