TY - GEN A1 - Azam, Hafiz Muhammad Husnain A1 - Rößling, Rosa Ilse A1 - Geithe, Christiane A1 - Khan, Muhammad Moman A1 - Dinter, Franziska A1 - Hanack, Katja A1 - Prüß, Harald A1 - Husse, Britta A1 - Roggenbuck, Dirk A1 - Schierack, Peter A1 - Rödiger, Stefan T1 - MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review T2 - Frontiers in Molecular Neuroscience N2 - Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells—all indicative of disease progression—before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer’s disease, Parkinson’s disease, Multiple sclerosis, Huntington’s disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies. KW - neurodegenerative diseases KW - microRNA KW - biomarkers KW - nervous system KW - diagnostic tools KW - therapeutic tools KW - protein post-translational modifications KW - limitations Y1 - 2024 U6 - https://doi.org/10.3389/fnmol.2024.1386735 SN - 1662-5099 VL - 17 PB - Frontiers Media S.A. ER - TY - GEN A1 - Frost, Fabian A1 - Weiss, Stefan A1 - Hertel, Johannes A1 - Rühlemann, Malte A1 - Bang, Corinna A1 - Franke, Andre A1 - Nauck, Matthias A1 - Dörr, Marcus A1 - Völzke, Henry A1 - Roggenbuck, Dirk A1 - Schierack, Peter A1 - Völker, Uwe A1 - Homuth, Georg A1 - Aghdassi, Ali A. A1 - Sendler, Matthias A1 - Lerch, Markus M. A1 - Weiss, Frank U. T1 - Fecal glycoprotein 2 is a marker of gut microbiota dysbiosis and systemic inflammation T2 - Gut Pathogens N2 - Background autoantigenic glycoprotein 2 (GP2) is an important component of the innate immune system which originates from the exocrine pancreas as well as from the small intestines. The relationship of GP2 with the intestinal microbiome as well as the systemic implications of increased fecal GP2 levels are, however, still unclear. Therefore, fecal samples from 2,812 individuals of the Study of Health in Pomerania (SHIP) were collected to determine GP2 levels (enzyme-linked immunosorbent assay) and gut microbiota profiles (16 S rRNA gene sequencing). These data were correlated and associated with highly standardised and comprehensive phenotypic data of the study participants. Results Fecal GP2 levels were increased in individuals with higher body mass index and smokers, whereas lower levels were found in case of preserved exocrine pancreatic function, female sex or a healthier diet. Moreover, higher GP2 levels were associated with increased serum levels of high-sensitivity C-reactive protein, loss of gut microbial diversity and an increase of potentially detrimental bacteria (Streptococcus, Haemophilus, Clostridium XIVa, or Collinsella). At the same time, predicted microbial pathways for the biosynthesis of beneficial short-chain fatty acids or lactic acid were depleted in individuals with high fecal GP2. Of note, GP2 exhibited a stronger association to overall microbiome variation than calprotectin. Conclusion Fecal GP2 is a biomarker of gut microbiota dysbiosis and associated with increased systemic inflammation. The intestines may be more important as origin for GP2 than pancreatic acinar cells. Future studies need to investigate the potential clinical value in disease specific patient cohorts. Y1 - 2024 U6 - https://doi.org/10.1186/s13099-024-00657-1 SN - 1757-4749 VL - 16 IS - 1 SP - 1 EP - 11 PB - Springer Science and Business Media LLC ER - TY - GEN A1 - Lopens, Steffi A1 - Schierack, Peter A1 - Krause, Jenny A1 - Piaszczyński, Michał A1 - Król, Robert A1 - Staroń, Robert A1 - Krupa, Łukasz A1 - Gutkowski, Krzysztof A1 - Kruk, Beata A1 - Grąt, Michał A1 - Krawczyk, Marek A1 - Patkowski, Waldemar A1 - Glaser, Fabian A1 - Rödiger, Stefan A1 - Grossmann, Kai A1 - Pająk, Jacek A1 - Milkiewicz, Piotr A1 - Lammert, Frank A1 - Zieniewicz, Krzysztof A1 - Schramm, Christoph A1 - Roggenbuck, Dirk A1 - Krawczyk, Marcin T1 - Antimicrobial glycoprotein 2 (GP2) in gallstones, bile fluid and peribiliary glands of patients with primary sclerosing cholangitis T2 - Clinica Chimica Acta Y1 - 2024 U6 - https://doi.org/10.1016/j.cca.2024.119841 SN - 0009-8981 VL - 562 SP - 1 EP - 8 PB - Elsevier BV ER - TY - GEN A1 - Geithe, Christiane A1 - Zeng, Bo A1 - Schmidt, Carsten A1 - Dinter, Franziska A1 - Roggenbuck, Dirk A1 - Lehmann, Werner A1 - Dame, Gregory A1 - Schierack, Peter A1 - Hanack, Katja A1 - Rödiger, Stefan T1 - A multiplex microchamber diffusion assay for the antibody-based detection of microRNAs on randomly ordered microbeads T2 - Biosensors and Bioelectronics: X Y1 - 2024 U6 - https://doi.org/10.1016/j.biosx.2024.100484 SN - 2590-1370 VL - 18 (2024) SP - 1 EP - 7 PB - Elsevier BV ER - 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 - TY - GEN A1 - Roei, Tulchinsky A1 - Boris, Gilburd A1 - Yehuda, Shovman A1 - Milena, Tocut A1 - Eleanor, Zeruya A1 - Ariel, Binyaminov A1 - Tima, Davidson A1 - Büttner, Thomas A1 - Nasser, Abdullah A1 - Michel, Juliane A1 - Rödiger, Stefan A1 - Schierack, Peter A1 - Howard, Amital A1 - Roggenbuck, Dirk A1 - Yehuda, Shoenfeld A1 - Ora, Shovman T1 - CytoBead ANA 2 assay : a novel method for the detection of antinuclear antibodies T2 - Scientific reports N2 - Detection of anti-nuclear autoantibodies (ANA) is based on a two-step algorithm including indirect immunofluorescence (IIF) on HEp2 cells and subsequent reflex/confirmatory testing for specific autoantibodies. Simultaneous cell- and microbead-based autoantibody detection by IIF may be utilized for the evaluation of systemic autoimmune rheumatic diseases (SARDs). In the present study, we assessed the performance of CytoBead ANA 2 in the detection of ANA and ANA-specific autoantibodies, compared to ANA IIF and BioPlex™ 2200. We also tested the ability of CytoBead ANA DFS-70 to identify dense-fine speckled (DFS) pattern associated with anti-DFS70 antibodies in non-SARDs patients. Hundred-twelve routine sera samples were assessed by manual CytoBead ANA 2 for the presence of ANA and specific autoantibodies. In parallel, these samples were analyzed by HEp2 ANA IIF test and a subsequent multiplexed assay BioPlex™ 2200 ANA. Twenty-nine ANA-positive samples obtained from non-SARDs patients and exhibiting DFS pattern by ANA IIF were further tested by CytoBead ANA DFS-70. A substantial agreement was observed between classical ANA IIF and manual CytoBead ANA 2 for the detection of ANA (k = 0.74). Discordant results were mainly associated with the presence of anti-SSA/Ro antibodies detected by CytoBead ANA 2 in ANA IIF negative patients. A good to almost perfect agreement was found between CytoBead ANA 2 and BioPlex™ 2200 for detection of specific antibodies with kappa values ranging from 0.70 to 0.90. Twenty samples (68.9%) obtained from 29 ANA IIF positive without SARDs patients exhibited DFS pattern in CytoBead ANA DFS-70, which confirmed the presence of anti-DFS70 antibodies. The diagnostic performance of manual CytoBead ANA 2 for ANA screening and detection of ANA specific antibodies is comparable to the diagnostic performance of ANA IIF followed by BioPlex™ 2200. This novel one-step assay enables simultaneous ANA screening and confirmation and represents a promising alternative approach to the time-consuming and costly two-tier ANA analysis. KW - Anti-nuclear antibodies KW - Anti-DFS70 antibodies KW - Indirect immunofluorescence KW - Multiplexed assay KW - CytoBead technology Y1 - 2025 U6 - https://doi.org/10.1038/s41598-025-04583-3 SN - 2045-2322 VL - 15 IS - 1 SP - 1 EP - 11 PB - Nature Publishing Group UK CY - London ER -