@article{GewiesGorkaBergmannetal.2014, author = {Gewies, Andreas and Gorka, Oliver and Bergmann, Hanna and Pechloff, Konstanze and Petermann, Franziska and Jeltsch, Katharina M. and Rudelius, Martina and Kriegsmann, Mark and Weichert, Wilko and Horsch, Marion and Beckers, Johannes and Wurst, Wolfgang and Heikenwalder, Mathias and Korn, Thomas and Heissmeyer, Vigo and Ruland, Juergen}, title = {Uncoupling Malt1 Threshold Function from Paracaspase Activity Results in Destructive Autoimmune Inflammation}, series = {Cell Reports}, volume = {9}, journal = {Cell Reports}, number = {4}, doi = {10.1016/j.celrep.2014.10.044}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114627}, pages = {1292-1305}, year = {2014}, abstract = {The paracaspase Malt1 is a central regulator of antigen receptor signaling that is frequently mutated in human lymphoma. As a scaffold, it assembles protein complexes for NF-kappa B activation, and its proteolytic domain cleaves negative NF-kappa B regulators for signal enforcement. Still, the physiological functions of Malt1-protease are unknown. We demonstrate that targeted Malt1-paracaspase inactivation induces a lethal inflammatory syndrome with lymphocyte-dependent neurodegeneration in vivo. Paracaspase activity is essential for regulatory T cell (Treg) and innate-like B cell development, but it is largely dispensable for overcoming Malt1-dependent thresholds for lymphocyte activation. In addition to NF-kappa B inhibitors, Malt1 cleaves an entire set of mRNA stability regulators, including Roquin-1, Roquin-2, and Regnase-1, and paracaspase inactivation results in excessive interferon gamma (IFN gamma) production by effector lymphocytes that drive pathology. Together, our results reveal distinct threshold and modulatory functions of Malt1 that differentially control lymphocyte differentiation and activation pathways and demonstrate that selective paracaspase blockage skews systemic immunity toward destructive autoinflammation.}, language = {en} } @article{ZhouWuchterEgereretal.2019, author = {Zhou, Xiang and Wuchter, Patrick and Egerer, Gerlinde and Kriegsmann, Mark and Mataityte, Aiste and Koelsche, Christian and Witzens-Harig, Mathias and Kriegsmann, Katharina}, title = {Role of virological serum markers in patients with both hepatitis B virus infection and diffuse large B-cell lymphoma}, series = {European Journal of Haematology}, volume = {103}, journal = {European Journal of Haematology}, number = {4}, doi = {10.1111/ejh.13300}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258442}, pages = {410-416}, year = {2019}, abstract = {Background Causality between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) was reported in various studies. However, the implication of different virological serum markers of HBV infection in patients with both HBV infection and DLBCL is not fully understood. The aim of this study was to investigate the impact of HBV markers on overall survival (OS) and progression-free survival (PFS) in patients with both HBV infection and DLBCL. Methods In this study, patients (n = 40) diagnosed with both HBV infection and DLBCL were identified between 2000 and 2017. Six patients with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) co-infection were excluded from this study. We retrospectively analyzed patients' demographic characteristics, treatment, and the prognostic impact of different HBV markers at first diagnosis of DLBCL (HBsAg, anti-HBs, HBeAg, anti-HBe, and HBV-DNA) on OS and PFS. Results The majority of patients (n = 21, 62\%) had advanced disease stage (III/IV) at diagnosis. In the first-line therapy, 24 patients (70\%) were treated with R-CHOP regimen (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone). HBeAg positive patients had a trend toward inferior OS and PFS compared with HBeAg negative patients. Anti-HBe positive patients had a statistically significant better OS and PFS compared with anti-HBe negative group (both P < .0001). Viremia with HBV-DNA ≥ 2 × 107 IU/L had a significant negative impact on OS and PFS (both P < .0001). Conclusion High activity of viral replication is associated with a poor survival outcome of patients with both HBV infection and DLBCL.}, language = {en} }