Letter
Medicine, General & Internal
Anna R. Schreiber, Dara L. Aisner, Jonathan A. Gutman
Summary: This article reports a case of fetal-induced graft-versus-host disease, in which the mother developed fever, pancytopenia, and rash 3 weeks after the delivery of twin sons that included transfusion.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Immunology
Hua Jiang, Denggang Fu, Alan Bidgoli, Sophie Paczesny
Summary: Allogeneic hematopoietic cell transplantation (allo-HCT) is crucial for treating hematological malignancies, but acute and chronic graft-versus-host disease (aGVHD and cGVHD) are major complications. Understanding the roles of T cell subsets in GVHD pathogenesis is essential for identifying new therapeutic targets and improving outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Linde Dekker, Evy Sanders, Caroline A. Lindemans, Coco de Koning, Stefan Nierkens
Summary: The recovery of naive T cells plays an important role in allo-HCT by functioning as both drivers and regulators in allogeneic reactions. Adequate reconstitution of naive T cells can improve GvHD prevention while maintaining GvL effects to lower relapse risk.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Shuang Fan, Wen-Xuan Huo, Yang Yang, Meng-Zhu Shen, Xiao-Dong Mo
Summary: This study reports the updated results of ruxolitinib as treatment for SR-GVHD and compares the efficacy and safety between children and adults. The findings suggest that ruxolitinib is an effective and safe treatment for SR-GVHD, and both children and adults can benefit from it.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Fathima A. Mohamed, Govindarajan Thangavelu, Stephanie Y. Rhee, Peter T. Sage, Roddy S. O'Connor, Jeffrey C. Rathmell, Bruce R. Blazar
Summary: The therapeutic efficacy of allo-HSCT is limited by the development of GVHD, with immune dysregulation leading to expansion of alloreactive cells and reduction in regulatory cells. New therapies are needed to restore the balance between effector and regulatory immune cells while preserving the beneficial graft-versus-tumor effect.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Kiyomi Mashima, Iekuni Oh, Ken Fujiwara, Junko Izawa, Norihito Takayama, Hirofumi Nakano, Yasufumi Kawasaki, Daisuke Minakata, Ryoko Yamasaki, Kaoru Morita, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kazuya Sato, Ken Ohmine, Shin-Ichiro Fujiwara, Nobuhiko Ohno, Yoshinobu Kanda
Summary: Anti-thymocyte globulin treatment effectively mitigated symptoms of graft-versus-host disease, reduced inflammatory cell infiltration, and prolonged survival; Alemtuzumab treatment modestly extended survival but also affected Tregs; Improvement after post-transplant cyclophosphamide treatment was minimal.
Review
Hematology
Noa G. Holtzman, Steven Z. Pavletic
Summary: Chronic graft-versus-host disease (cGVHD) is a systemic complication of allogeneic haematopoietic stem cell transplantation that can lead to increased morbidity and mortality. Despite limited curative treatment options, recent collaborative research efforts have led to discovery of new second-line therapies. Comprehensive and sustained multidisciplinary efforts are crucial for successful management of cGVHD.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Immunology
Takanori Teshima, Geoffrey R. R. Hill
Summary: Allogeneic hematopoietic cell transplantation is an effective treatment for hematologic malignancies, but graft-versus-host disease remains a significant complication. Insights from animal models have led to new therapeutic approaches in the clinic, focusing on histocompatibility matching, GVHD prophylaxis, and novel inhibitors for cytokine signaling to improve patient outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shinri Sato, Eisuke Shimizu, Jingliang He, Mamoru Ogawa, Kazuki Asai, Hiroyuki Yazu, Robert Rusch, Mio Yamane, Fan Yang, Shinji Fukuda, Yutaka Kawakami, Kazuo Tsubota, Yoko Ogawa
Summary: In this study, it was found in a mouse model that gentamicin (GM) significantly suppressed systemic cGVHD phenotypes and ocular manifestations, and reduced inflammatory cell infiltration and fibrosis in cGVHD-targeted organs. Although GM maintained higher levels of regulatory T cells, there were fewer Th17 cells and IL-6-producing macrophages in cGVHD-targeted organs. These findings suggest that orally administered GM may have positive effects in a cGVHD mouse model.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Geoffrey R. Hill, Brian C. Betts, Victor Tkachev, Leslie S. Kean, Bruce R. Blazar
Summary: The study explores the pathophysiology of GVHD during allogeneic transplantation, including host/donor cell effectors, immune system and cytokine imbalance. It summarizes the translational application of these findings in designing novel therapies for GVHD prevention and treatment.
ANNUAL REVIEW OF IMMUNOLOGY, VOL 39
(2021)
Review
Cell Biology
Konradin F. Muskens, Caroline A. Lindemans, Mirjam E. Belderbos
Summary: GvHD is a major complication of HCT, causing severe hematopoietic dysfunction. Immune activation during GvHD damages hematopoietic stem cells and their niche in the bone marrow, leading to reduced functionality. Complications and treatments associated with HCT exacerbate hematopoietic dysfunction.
Article
Hematology
Jiapei Liu, Zhiping Fan, Na Xu, Jieyu Ye, Yanqiu Chen, Ruoyang Shao, Yiming Sun, Qiaoyuan Wu, Qifa Liu, Hua Jin
Summary: This study evaluated the effects of ruxolitinib compared with basiliximab in the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD). The results showed that ruxolitinib had a higher overall response rate and effectively prevented chronic GVHD (cGVHD), leading to improved survival rates.
ANNALS OF HEMATOLOGY
(2023)
Article
Hematology
Jiapei Liu, Zhiping Fan, Na Xu, Jieyu Ye, Yanqiu Chen, Ruoyang Shao, Yiming Sun, Qiaoyuan Wu, Qifa Liu, Hua Jin
Summary: This study retrospectively evaluated the effects of ruxolitinib compared with basiliximab for steroid-refractory acute graft-versus-host disease (SR-aGVHD). The results showed that ruxolitinib had higher overall response and complete response rates, as well as lower incidence of chronic GVHD. Ruxolitinib also improved overall survival and failure-free survival rates. In addition, ruxolitinib significantly reduced the occurrence of EBV viremia. Therefore, ruxolitinib should be recommended for the treatment of SR-aGVHD.
ANNALS OF HEMATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Alfonso Rodriguez-Gil, Estrella Carrillo-Cruz, Cristina Marrero-Cepeda, Guillermo Rodriguez, Jose A. Perez-Simon
Summary: Vitamin D plays a dual role in the immune system and tumor cells, potentially decreasing graft-versus-host disease and relapse rates.
Review
Gastroenterology & Hepatology
Fei Gao, Hengwei Wu, Limengmeng Wang, Yanmin Zhao, He Huang
Summary: Despite advancements in HSCT, GVHD, especially intestinal GVHD, still poses a significant challenge to the procedure. Traditionally, GVHD has been seen as an immune response, with the intestine as a target. However, factors such as altered intestinal microbiome and epithelial damage contribute to intestinal damage after transplantation. This review summarizes these factors and explores the potential of remodeling intestinal homeostasis in GVHD management.
Review
Immunology
Stephanie Kim, Pavan Reddy
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Zesen Lin, Richard King, Vi Tang, Greggory Myers, Ginette Balbin-Cuesta, Ann Friedman, Beth McGee, Karl Desch, Ayse Bilge Ozel, David Siemieniak, Pavan Reddy, Brian Emmer, Rami Khoriaty
MOLECULAR AND CELLULAR BIOLOGY
(2020)
Article
Oncology
Katherine Oravecz-Wilson, Corinne Rossi, Cynthia Zajac, Yaping Sun, Lu Li, Thomas Decoville, Hideaki Fujiwara, Stephanie Kim, Daniel Peltier, Pavan Reddy
Summary: Autophagy plays a crucial role in regulating allo-immunity in T cells by affecting proliferation and effector functions. ATG5-dependent autophagy can reduce GVHD while maintaining GVT responses in transplantation settings.
Article
Medicine, Research & Experimental
Stephanie Kim, Rami Khoriaty, Lu Li, Madison McClune, Theodosia A. Kalfa, Julia Wu, Daniel Peltier, Hideaki Fujiwara, Yaping Sun, Katherine Oravecz-Wilson, Richard A. King, David Ginsburg, Pavan Reddy
Summary: The activation of T cells leads to increased trafficking via the ER-to-Golgi pathway, which is crucial for the regulation of T cell secretome. Deficiency of SEC23B may impair T cell functions, while increased levels of SEC23A in CDAII patients' T cells contribute to maintaining their functions.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Cell Biology
Daniel Peltier, Molly Radosevich, Visweswaran Ravikumar, Sethuramasundaram Pitchiaya, Thomas Decoville, Sherri C. Wood, Guoqing Hou, Cynthia Zajac, Katherine Oravecz-Wilson, David Sokol, Israel Henig, Julia Wu, Stephanie Kim, Austin Taylor, Hideaki Fujiwara, Yaping Sun, Arvind Rao, Arul M. Chinnaiyan, Daniel R. Goldstein, Pavan Reddy
Summary: This study identified Linc00402 as a significant regulator of allogeneic T cell function, enhancing proliferative response to allogeneic stimuli by increasing ERK1 and ERK2 activity, FOS nuclear accumulation, and expression of interleukin-2 and Egr-1. Additionally, Linc00402 was decreased in patients who developed acute graft-versus-host disease after transplantation.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Samantha N. Devenport, Rashi Singhal, Megan D. Radyk, Joseph G. Taranto, Samuel A. Kerk, Brandon Chen, Joshua W. Goyert, Chesta Jain, Nupur K. Das, Katherine Oravecz-Wilson, Li Zhang, Joel K. Greenson, Y. Eugene Chen, Scott A. Soleimanpour, Pavan Reddy, Costas A. Lyssiotis, Yatrik M. Shah
Summary: The study demonstrates the importance of autophagy in cell growth and tumor development in colorectal cancer, with inhibition of autophagy leading to suppressed tumor growth. Furthermore, autophagy plays a critical role in maintaining mitochondrial metabolites for promoting growth in colon cancer cells.
Article
Biochemistry & Molecular Biology
Roshan Kumar, Aaron P. Landry, Arkajit Guha, Victor Vitvitsky, Ho Joon Lee, Keisuke Seike, Pavan Reddy, Costas A. Lyssiotis, Ruma Banerjee
Summary: The dual roles of H2S as a respiratory substrate and toxin raise questions about how it is cleared when the electron transport chain is inhibited. This study discovered a newly established redox cycle between SQOR and complex II at high H2S concentrations, which plays a significant role in prioritizing H2S oxidation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Immunology
Hideaki Fujiwara, Keisuke Seike, Michael D. Brooks, Anna Mathew, Ilya Kovalenko, Anupama Pal, Ho-Joon Lee, Daniel Peltier, Stephanie Kim, Chen Liu, Katherine Oravecz-Wilson, Lu Li, Yaping Sun, Jaeman Byun, Yoshinobu Maeda, Max S. Wicha, Tom Saunders, Alnawaz Rehemtulla, Costas A. Lyssiotis, Subramanian Pennarthur, Pavan Reddy
Summary: The alteration of IEC-specific mitochondrial complex II component SDHA plays a critical role in regulating the severity of T cell-mediated intestinal diseases, including graft-versus-host disease, inflammatory bowel disease and immune checkpoint blockade-mediated colitis.
Article
Multidisciplinary Sciences
Richard King, Zesen Lin, Ginette Balbin-Cuesta, Gregg Myers, Ann Friedman, Guojing Zhu, Beth McGee, Thomas L. Saunders, Ryo Kurita, Yukio Nakamura, James Douglas Engel, Pavan Reddy, Rami Khoriaty
Summary: The expression of full SEC23A protein from endogenous regulatory elements of Sec23b can completely rescue the SEC23B-deficient mouse phenotype, while erythroid-specific deletion of all four Sec23 alleles in mice results in mid-embryogenesis death with features of CDAII. The study also suggests a novel therapeutic strategy for CDAII by increasing the expression of SEC23A in human erythroid cells.
Article
Hematology
John M. Magenau, Dan Peltier, Mary Riwes, Attaphol Pawarode, Brian Parkin, Thomas Braun, Sarah Anand, Monalisa Ghosh, John Maciejewski, Gregory Yanik, Sung Won Choi, Moshe Talpaz, Pavan Reddy
Summary: A strong graft-versus-leukemia (GVL) response is essential in preventing relapse after allogeneic hematopoietic cell transplantation (HCT). Preclinical studies showed that type 1 interferon (IFN-a) enhances cross-presentation of leukemia-specific antigens, leading to amplified GVL. Clinical trials with pegylated IFN-a (pegIFNa) in high-risk AML patients undergoing HCT demonstrated feasibility of prophylactic pegIFNa administration without increased toxicity and potential reduction in leukemia relapse post-transplantation.
Review
Immunology
Daniel C. Peltier, Alexis Roberts, Pavan Reddy
Summary: Despite the increasing understanding of how protein-coding genes influence immune responses, the molecular mechanisms of immune regulation are still not fully understood. Long noncoding RNAs (lncRNAs) have various functions in regulating gene expression and cellular functions. Although the functions of most lncRNAs are unknown, some have been identified as important immune regulators. Therefore, further research on the role of lncRNAs in the mammalian immune system and their tissue-specific expression may lead to more precise therapeutics and diagnostics for immune disorders.
TRENDS IN IMMUNOLOGY
(2022)
Article
Physiology
Kelly R. VanDenBerg, Katherine Oravecz-Wilson, Lauren Krolikowski, Valerie Hill, Pavan Reddy, Zachary T. Freeman
Summary: This study investigated the impact of commercial automated genotyping and centralized breeding management on overall breeding colony productivity in a colony of multiple genetically engineered mouse models (GEMMs). The results showed that outsourcing genotyping and receiving assistance from the laboratory animal care team can significantly increase the production of breeding cages and mice, which is driven primarily by an increase in the number of breeding cages in each colony.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yaping Sun, Gabrielle A. Dotson, Lindsey A. Muir, Scott Ronquist, Katherine Oravecz-Wilson, Daniel Peltier, Keisuke Seike, Lu Li, Walter Meixner, Indika Rajapake, Pavan Reddy
Summary: This study reveals that WAPL deficiency affects the 3D structure and function of the genome in mature T cells, with implications for their biological and clinical characteristics.
Article
Biochemistry & Molecular Biology
Anna Mathew, Lixia Zeng, Kevin B. Atkins, Kiana N. Sadri, Jaeman Byun, Hideaki Fujiwara, Pavan Reddy, Subramaniam Pennathur
Summary: The study demonstrates a decrease in atherosclerosis in CKD mice with MPO deletion in bone marrow cells, strongly implicating bone-marrow-derived MPO in the pathogenesis of CKD atherosclerosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Hematology
Kirsten M. Williams, Yoshihiro Inamoto, Annie Im, Betty Hamilton, John Koreth, Mukta Arora, Iskra Pusic, Jacqueline W. Mays, Paul A. Carpenter, Leo Luznik, Pavan Reddy, Jerome Ritz, Hildegard Greinix, Sophie Paczesny, Bruce R. Blazar, Joseph Pidala, Corey Cutler, Daniel Wolff, Kirk R. Schultz, Steven Z. Pavletic, Stephanie J. Lee, Paul J. Martin, Gerard Socie, Stefanie Sarantopoulos
Summary: Preventing chronic GVHD remains challenging due to poorly understood pathways that incite the condition. Interventions at the time of transplantation and identification of initiation pathways are crucial for developing targeted prevention strategies. Further research into the mechanisms underlying chronic GVHD development and considerations for future trial design are highlighted as high research priorities.
TRANSPLANTATION AND CELLULAR THERAPY
(2021)