TY  - JOUR
A1  - Zhou, Xiang
A1  - Wuchter, Patrick
A1  - Egerer, Gerlinde
A1  - Kriegsmann, Mark
A1  - Mataityte, Aiste
A1  - Koelsche, Christian
A1  - Witzens-Harig, Mathias
A1  - Kriegsmann, Katharina
T1  - Role of virological serum markers in patients with both hepatitis B virus infection and diffuse large B-cell lymphoma
JF  - European Journal of Haematology
N2  - 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.
KW  - hepatitis B virus
KW  - diffuse large B-cell lymphoma
KW  - prognosis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258442
VL  - 103
IS  - 4
ER  - 
TY  - JOUR
A1  - Gewies, Andreas
A1  - Gorka, Oliver
A1  - Bergmann, Hanna
A1  - Pechloff, Konstanze
A1  - Petermann, Franziska
A1  - Jeltsch, Katharina M.
A1  - Rudelius, Martina
A1  - Kriegsmann, Mark
A1  - Weichert, Wilko
A1  - Horsch, Marion
A1  - Beckers, Johannes
A1  - Wurst, Wolfgang
A1  - Heikenwalder, Mathias
A1  - Korn, Thomas
A1  - Heissmeyer, Vigo
A1  - Ruland, Juergen
T1  - Uncoupling Malt1 Threshold Function from Paracaspase Activity Results in Destructive Autoimmune Inflammation
JF  - Cell Reports
N2  - 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.
KW  - helper T-cells
KW  - combined immunodeficiency
KW  - messenger RNA
KW  - roquin
KW  - mice
KW  - NF-KAPPA-B
KW  - lymphoid-tissue
KW  - activation
KW  - cleavage
KW  - mutations
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114627
VL  - 9
IS  - 4
ER  -