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?
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 correspondin...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6166 |
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| author | Victoria Liedtke Laura Rose Rico Hiemann Abdullah Nasser Stefan Rödiger Alena Bonaventura Laura Winkler Mandy Sowa Michael Stöckle Peter Schierack Kerstin Junker Dirk Roggenbuck |
| author_facet | Victoria Liedtke Laura Rose Rico Hiemann Abdullah Nasser Stefan Rödiger Alena Bonaventura Laura Winkler Mandy Sowa Michael Stöckle Peter Schierack Kerstin Junker Dirk Roggenbuck |
| author_sort | Victoria Liedtke |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T05:36:10Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:36:10Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-beeac7d0aacf48abbd274b5bd741158e2023-11-17T16:47:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247616610.3390/ijms24076166Over-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?Victoria Liedtke0Laura Rose1Rico Hiemann2Abdullah Nasser3Stefan Rödiger4Alena Bonaventura5Laura Winkler6Mandy Sowa7Michael Stöckle8Peter Schierack9Kerstin Junker10Dirk Roggenbuck11Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, GermanyGA Generic Assays GmbH, 15827 Blankenfelde-Mahlow, GermanyFaculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, GermanyMedipan GmbH, 15827 Blankenfelde-Mahlow, GermanyFaculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, GermanyDepartment of Urology and Pediatric Urology, Saarland University, 66424 Homburg, GermanyFaculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, GermanyGA Generic Assays GmbH, 15827 Blankenfelde-Mahlow, GermanyDepartment of Urology and Pediatric Urology, Saarland University, 66424 Homburg, GermanyFaculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, GermanyDepartment of Urology and Pediatric Urology, Saarland University, 66424 Homburg, GermanyFaculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, GermanyLens 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.https://www.mdpi.com/1422-0067/24/7/6166LEDGF/p75autoimmunityCRISPR/Cas9dsDNAmDNA |
| spellingShingle | Victoria Liedtke Laura Rose Rico Hiemann Abdullah Nasser Stefan Rödiger Alena Bonaventura Laura Winkler Mandy Sowa Michael Stöckle Peter Schierack Kerstin Junker Dirk Roggenbuck 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? International Journal of Molecular Sciences LEDGF/p75 autoimmunity CRISPR/Cas9 dsDNA mDNA |
| title | 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? |
| title_full | 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? |
| title_fullStr | 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? |
| title_full_unstemmed | 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? |
| title_short | 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? |
| title_sort | 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 |
| topic | LEDGF/p75 autoimmunity CRISPR/Cas9 dsDNA mDNA |
| url | https://www.mdpi.com/1422-0067/24/7/6166 |
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