Article
Immunology
Shokichi Takahama, Sachiyo Yoshio, Yuji Masuta, Hirotomo Murakami, Ryotaro Sakamori, Shun Kaneko, Takashi Honda, Miyako Murakawa, Masaya Sugiyama, Masayuki Kurosaki, Yasuhiro Asahina, Tetsuo Takehara, Victor Appay, Tatsuya Kanto, Takuya Yamamoto
Summary: This study explored the traits of activated CD8(+) T cells and HBV-specific CD8(+) T cells in patients with chronic hepatitis B undergoing NUC therapy. Results revealed that patients with higher HBsAg levels had CD8(+) T cell clusters with cytolytic functions, while HBcore-specific CD8(+) T cells exhibited greater polyfunctionality and a subset of these cells with lower cytolytic potential was negatively correlated with HBsAg levels.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Caroline Lefeuvre, Helene Le Guillou-Guillemette, Alexandra Ducancelle
Summary: Chronic HBV infection is a common factor associated with HCC, with studies showing that the HBc protein plays a significant role in affecting pathways involved in HCC development, such as migration, proliferation, apoptosis, metabolism, and immune responses. HBc can also promote HCC metastasis by modulating host gene expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Ja Yeon Kim Chu, Yu-Chen Chuang, Kuen-Nan Tsai, Jessica Pantuso, Yuji Ishida, Takeshi Saito, Jing-hsiung James Ou
Summary: This study reveals the association between autophagic membranes and HBV replication. The core protein is associated with phagophores, while the precore protein derivative is associated with autophagosomes. Autophagic membranes play different roles in the trafficking of core and precore proteins, as well as the assembly and release of HBV particles.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Gastroenterology & Hepatology
Tobias Boettler, Benedikt Csernalabics, Henrike Salie, Hendrik Luxenburger, Lara Wischer, Elahe Salimi Alizei, Katharina Zoldan, Laurenz Krimmel, Peter Bronsert, Marius Schwabenland, Marco Prinz, Carolin Mogler, Christoph Neumann-Haefelin, Robert Thimme, Maike Hofmann, Bertram Bengsch
Summary: This case report highlights the occurrence of autoimmune hepatitis episodes following COVID-19 vaccination in a patient with distinctive T cell-dominant immune-mediated hepatitis. Liver tissue analysis revealed an immune infiltrate with activated cytotoxic CD8 T cells predominantly distributed, indicating a unique pathomechanism associated with vaccination-induced antigens.
JOURNAL OF HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Wenshi Wang, Florian A. Lempp, Franziska Schlund, Lisa Walter, Charlotte C. Decker, Zhenfeng Zhang, Yi Ni, Stephan Urban
Summary: Research has shown that HDVs from different genotypes replicate with varying efficacies. Variations in HDV genomes and HBV envelope proteins are major determinants of HDV egress and entry efficacy.
JOURNAL OF HEPATOLOGY
(2021)
Article
Immunology
Si Xie, Liu Yang, Xiaoyue Bi, Wen Deng, Tingting Jiang, Yanjie Lin, Shiyu Wang, Lu Zhang, Ruyu Liu, Min Chang, Shuling Wu, Yuanjiao Gao, Hongxiao Hao, Ge Shen, Mengjiao Xu, Xiaoxue Chen, Leiping Hu, Yao Lu, Rui Song, Yao Xie, Minghui Li
Summary: The activation of CD8+ T lymphocytes is associated with the occurrence of acute and chronic hepatitis B. CD8+ T lymphocytes play an important role in the development of hepatitis B, and their activation status is correlated with the progression of the disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Virology
Youquan Zhong, Chuanjian Wu, Zaichao Xu, Yan Teng, Li Zhao, Kaitao Zhao, Jingjing Wang, Wen Wang, Qiong Zhan, Chengliang Zhu, Xinwen Chen, Kaiwei Liang, Xiaoming Cheng, Yuchen Xia
Summary: This study showed that HBV core protein (HBc) has no effect on epigenetic regulation of cccDNA and does not participate in cccDNA transcription. Novel cccDNA-targeting therapeutics are needed for an HBV cure.
JOURNAL OF VIROLOGY
(2022)
Article
Gastroenterology & Hepatology
William Bremer, Heather Blasczyk, Xin Yin, Eduardo Salinas, Arash Grakoui, Zongdi Feng, Christopher Walker
Summary: The study found that CD8+ T cells can assist in controlling HEV infection in untreated macaques, but the simultaneous appearance of CD8+ T cells with HEV clearance may support the role of this subset in controlling virus replication. However, virus clearance in the absence of CD8+ T cells indicates that neutralizing antibodies and/or CD4+ T cells may act autonomously to inhibit HEV replication.
JOURNAL OF HEPATOLOGY
(2021)
Review
Immunology
Wen Hou, Xiaoli Wu
Summary: This study investigates the roles of gamma delta T cells in HBV and HCV infections, discussing the different roles they play in the progression of liver diseases at various stages.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Zhen Xun, Jinpiao Lin, Qingqing Yu, Can Liu, Jinlan Huang, Hongyan Shang, Jianhui Guo, Yuchen Ye, Wennan Wu, Yongbin Zeng, Songhang Wu, Siyi Xu, Tianbin Chen, Jing Chen, Qishui Ou
Summary: Bile acids (BAs), especially taurocholic acid (TCA), are significantly elevated in HBeAg-positive chronic hepatitis B (CHB) patients and inhibit the response to pegylated interferon-alpha (PegIFN alpha) therapy. These BAs reduce the number, proportion, and effector functions of CD3(+)CD8(+) T cells and natural killer (NK) cells in CHB patients.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Biophysics
Suchanat Boonkaew, Abdulhadee Yakoh, Nattaya Chuaypen, Pisit Tangkijvanich, Sirirat Rengpipat, Weena Siangproh, Orawon Chailapakul
Summary: Electrochemical paper-based analytical devices (ePADs) are simple, portable, and low-cost analytical devices for point-of-care testing of clinical biomarkers. A sequential ePAD has been developed for simultaneous detection of hepatitis B surface antigen and hepatitis C core antigen by integrating dual flow behaviors, avoiding the need for complex multi-step reagent manipulation by the user. The proposed ePAD shows high promise as an easy-to-use, portable, and extendable sensor for other multiplex biological assays.
BIOSENSORS & BIOELECTRONICS
(2021)
Article
Immunology
Yanchen Ma, Xiaoyi Liu, Haonan Lou, Liang Chen, Weiying He, Qingqing Pan, Dandan Liao, Juanhua Li, Jingran Wu, Rongzhu Xiong, Sihua Liu, Manling Luo, Fei Wu, Jing Chen, Zhihua Liu, Libo Tang, Yongyin Li, Yunfei Gao
Summary: This study found that the function of decidual CD8(+) T cells is compromised in term pregnant women with chronic HBV infection, supporting the necessity and importance of antiviral intervention in preventing mother-to-child transmission of HBV.
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2022)
Article
Virology
Xupeng Hong, Laurie Luckenbaugh, Megan Mendenhall, Renae Walsh, Liza Cabuang, Sally Soppe, Peter A. Revill, Dara Burdette, Becket Feierbach, William Delaney, Jianming Hu
Summary: HBcrAg is an emerging peripheral marker for monitoring intrahepatic viral activities in chronic HBV infection, comprising HBc, HBeAg, and PreC components with diverse proteolytic processing and genotype-specific variations. HBeAg is the predominant form in HBeAg-positive patients and shows positive correlations with PreC and HBcrAg levels, suggesting distinct functions and applications for each component in reflecting viral activities.
JOURNAL OF VIROLOGY
(2021)
Article
Gastroenterology & Hepatology
Xiu-Mei Chi, Xiao-Mei Wang, Zhong-Feng Wang, Rui-Hong Wu, Xiu-Zhu Gao, Hong-Qin Xu, Yan-Hua Ding, Jun-Qi Niu
Summary: The study found that serum qHBcrAg levels were correlated with virological markers of HBV in patients with chronic hepatitis B, and could be used to predict HBeAg seroconversion.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Gastroenterology & Hepatology
Kyeong Deok Kim, Ji Eun Lee, Jong Man Kim, Okjoo Lee, Na Young Hwang, Jinsoo Rhu, Gyu-Seong Choi, Kyunga Kim, Jae-Won Joh
Summary: The use of anti-HBc-positive donors for liver transplantation does not affect patient survival rates, while HBIG monoprophylaxis effectively reduces the risk of DNH. Furthermore, the long-term cost burden for patients in Korea is lower due to the national insurance system.
CLINICAL AND MOLECULAR HEPATOLOGY
(2021)
Article
Immunology
Andreas Walker, Torsten Houwaart, Patrick Finzer, Lutz Ehlkes, Alona Tyshaieva, Maximilian Damagnez, Daniel Strelow, Ashley Duplessis, Jessica Nicolai, Tobias Wienemann, Teresa Tamayo, Malte Kohns Vasconcelos, Lisanna Huelse, Katrin Hoffmann, Nadine Luebke, Sandra Hauka, Marcel Andree, Martin P. Daeumer, Alexander Thielen, Susanne Kolbe-Busch, Klaus Goebels, Rainer Zotz, Klaus Pfeffer, Joerg Timm, Alexander T. Dilthey
Summary: Tracing SARS-CoV-2 population transmission chains remains a major challenge, but this study presents an integrated system of genomic surveillance that is capable of detecting infection chains in a large city during ongoing community transmission. The system combines viral surveillance sequencing, genetically based identification of infection clusters, integration of public health authority contact tracing data, and a user-friendly dashboard application. This integrated system can contribute to the monitoring and potentially improve the management of SARS-CoV-2 transmission in the population.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Jan Gravemeyer, Ivelina Spassova, Monique E. Verhaegen, Andrzej A. Dlugosz, Daniel Hoffmann, Anja Lange, Juergen C. Becker
Summary: Analysis of DNA methylation suggests a common epithelial origin of UV- and VP-MCC cell lines.
Article
Immunology
Artur Kibler, Bettina Budeus, Ralf Kueppers, Marc Seifert
Summary: The composition of human splenic marginal zone (sMZ) B cells changes significantly with age, with a major population of lowly Ig-mutated CD27neg but antigen-experienced B cells early in life.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Ivelina Spassova, Selma Ugurel, Linda Kubat, Lisa Zimmer, Patrick Terheyden, Annalena Mohr, Hannah Bjorn Andtback, Lisa Villabona, Ulrike Leiter, Thomas Eigentler, Carmen Loquai, Jessica C. Hassel, Thilo Gambichler, Sebastian Haferkamp, Peter Mohr, Claudia Pfoehler, Lucie Heinzerling, Ralf Gutzmer, Jochen S. Utikal, Kai Horny, Hans-Ulrich Schildhaus, Daniel Habermann, Daniel Hoffmann, Dirk Schadendorf, Juergen Christian Becker
Summary: This multicenter retrospective study of 114 unresectable MCC patients examined clinical and molecular characteristics to identify factors associated with a favorable response to PD-1/PD-L1 ICI therapy. Findings highlighted the absence of immunosuppression, limited number of tumor-involved organs, and a predominance of CD8(+) T-CM among TIL as key baseline parameters influencing therapy response in advanced MCC patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemical Research Methods
Daniel Habermann, Hadi Kharimzadeh, Andreas Walker, Yang Li, Rongge Yang, Rolf Kaiser, Zabrina L. Brumme, Jorg Timm, Michael Roggendorf, Daniel Hoffmann
Summary: The study presents a Bayesian regression model for the detection of immune escape mutations in viruses, which integrates various information sources and provides interpretable quantitative information on mutation candidates. The model performs well in detecting mutations in datasets from individuals infected with different viruses.
Review
Gastroenterology & Hepatology
Reem Hoblos, Helenie Kefalakes
Summary: Infection with hepatitis D virus is the most severe form of chronic viral hepatitis and affects over 12 million people worldwide. Chronic HDV infection can lead to liver cirrhosis and hepatocellular carcinoma in approximately 70% of patients within 15 years. Recent evidence suggests that the interaction between different components of the immune system plays a crucial role in viral control and may also be involved in the development of liver diseases.
LIVER INTERNATIONAL
(2023)
Article
Immunology
Anne-Charlotte Antoni, Ekaterina Pylaeva, Bettina Budeus, Jadwiga Jablonska, Ludger Klein-Hitpass, Marcel Dudda, Stefanie B. Flohe
Summary: CD8(+) T cells sense TLR2 signals and control the number and function of de novo differentiating DCs in the bone marrow during sepsis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Artur Kibler, Marc Seifert, Bettina Budeus
Summary: In this review, the age-related changes of human splenic B cell composition and molecular evidence of immune maturation are summarized. The contribution of these changes on splenic protective function is discussed. The specialized B cell subpopulation in the splenic marginal zone (sMZ) recruits and archives memory B cells from immune responses throughout the organism. The quality of sMZ B cell responses is augmented by germinal center (GC)-dependent maturation of memory B cells during childhood, but likely contributes to waning of splenic protective function in old age.
IMMUNOLOGY LETTERS
(2023)
Article
Multidisciplinary Sciences
Fabian Gude, Jurij Froese, Dominique Manikowski, Daniele Di Iorio, Jean-Noel Grad, Seraphine Wegner, Daniel Hoffmann, Melissa Kennedy, Ralf P. Richter, Georg Steffes, Kay Grobe
Summary: Cellular differentiation is determined by concentration gradients of morphogens. Hedgehog (Hh) morphogens spread away from their source to direct growth and pattern formation in Drosophila wing and eye discs. The study shows that Hh can interact with heparan sulfate (HS) chains to temporarily cross-link them and this interaction is crucial for Hh gradient formation.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Simon Dubler, Michael Etringer, Markus A. Weigand, Thorsten Brenner, Stefan Zimmermann, Paul Schnitzler, Bettina Budeus, Fabian Rengier, Paulina Kalinowska, Yuan Lih Hoo, Christoph Lichtenstern
Summary: This study evaluated the outcome relevance of adequately treated putative invasive pulmonary aspergillosis (pIPA) in critically ill patients. The results showed that adequately treated pIPA did not increase the risk of death or unfavourable outcomes.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, General & Internal
Battur Magvan, Anne Alina Kloeble, Johannes Ptok, Daniel Hoffmann, Daniel Habermann, Anuujin Gantumur, Martha Paluschinski, Gerelmaa Enebish, Vera Balz, Johannes C. C. Fischer, Battogtokh Chimeddorj, Andreas Walker, Joerg Timm
Summary: The molecular epidemiology of HDV in Mongolia reveals high diversity with multiple subtypes and recent transmission events, while CD8(+) T cells exert immunological selection pressure on the virus.
FRONTIERS IN MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Bettina Roeder, Hannah Fahnenstiel, Simon Schaefer, Bettina Budeus, Maria Dampmann, Melanie Eichhorn, Sieglinde Angermueller, Claudia Brost, Thomas H. Winkler, Marc Seifert, Lars Nitschke
Summary: Loss of Siglec-G leads to increased severity and earlier onset of CLL in mice, while overexpression of Siglec-G on B cells protects against CLL development. Furthermore, downregulation of the human ortholog Siglec-10 is observed on the surface of human CLL cells. These findings highlight the critical role of Siglec-G in disease progression and suggest a potential similar mechanism for Siglec-10 in human CLL.
Article
Immunology
Ralf Kueppers, Bettina Budeus, Sylvia Hartmann, Martin-Leo Hansmann
Summary: CD30(+) B cells represent a distinct B-cell differentiation stage with features of strong activation. Studies have found that CD30(+) B cells can be more numerous in some cases of reactive lymphadenitis, and they are a heterogeneous population of polyclonal B cells, including both mutated and unmutated B-cells. These cell-rich CD30(+) B-cell populations do not represent precursor lesions of Hodgkin lymphoma.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Bettina Budeus, Kristian Unger, Julia Hess, Hanna Sentek, Diana Klein
Summary: MSCs are the most promising stem cell type for cell-based therapies in regenerative medicine due to their potential to differentiate into organ-specific cells and their ability to foster tissue regeneration through secretion of growth factors and cytokines. The study identified differentially expressed genes between MSCs and fibroblasts, highlighting the role of KRAS signaling and wound healing in MSCs' regenerative capacity. The HOX code was established for both MSCs and fibroblasts, and DNA methylation profiles revealed potential biomarkers.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Alexander Hoeing, Robin Struth, Christine Beuck, Neda Rafieiolhosseini, Daniel Hoffmann, Roland H. Stauber, Peter Bayer, Jochen Niemeyer, Shirley K. Knauer
Summary: Therapy resistance remains a challenge for the clinics. Dual-active chemicals that can simultaneously inhibit independent functions in disease-relevant proteins are highly desired but difficult to achieve. In this study, we successfully targeted the unique protease threonine aspartase 1 by designing precise bisphosphate ligands to inhibit additional steps required for its protease activity. We reported a bisphosphate anionic bivalent inhibitor 11d, which selectively bound to the basic nuclear localization signal cluster of the protease with high affinity, disrupting its interaction and function with Importin alpha. This inhibitor also affected the protease's catalytic substrate trans-cleavage activity and demonstrated inhibition of threonine aspartase 1 in living tumor cells. Our findings provide evidence that interference with independent key functions in a disease-relevant protein by an inhibitor binding to a single site is possible.