Review
Hematology
Mikhail V. Ovanesov, Joseph W. Jackson, Basil Golding, Timothy K. Lee
Summary: This article discusses the factors to consider when choosing an assay for potency assignment and postadministration monitoring of new factor products, including the validity of the assay calibrated with the IS, the meaning of potency values in IU, standards of care for patients, clinical relevance between the assigned potency value and recovery value from clinical laboratories, and patient safety.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Immunology
Glaivy Batsuli, Jasmine Ito, Elizabeth S. York, Courtney Cox, Wallace Baldwin, Surinder Gill, Pete Lollar, Shannon L. Meeks
Summary: This study analyzed the internalization of FVIII complexed with epitope-mapped FVIII-specific IgG monoclonal antibodies by murine bone marrow-derived dendritic cells (BMDCs) in vitro, as well as the antibody development in hemophilia A (FVIII-/-) mice injected with FVIII-IC over time. The results showed that certain FVIII-IC subsets modulate the humoral response to FVIII in an epitope-dependent manner.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Amber Vander Kooi, Shuaishuai Wang, Meng-Ni Fan, Alex Chen, Junping Zhang, Chun-Yu Chen, Xiaohe Cai, Barbara A. Konkle, Weidong Xiao, Lei Li, Carol H. Miao
Summary: The N-glycosylation of FVIII has a significant impact on its immunogenicity, as shown in this study. Gene mutations were introduced to eliminate glycosylation at potential sites, and it was found that FVIII activity remained stable while immune responses varied. A specific glycopeptide epitope surrounding one of the glycosylation sites was identified and characterized for its activation of T cells.
Article
Hematology
Anne-Fleur Zwagemaker, Fabienne R. Kloosterman, Samantha C. Gouw, Sara Boyce, Paul Brons, Marjon H. Cnossen, Peter W. Collins, Jeroen Eikenboom, Charles Hay, Rutger C. C. Hengeveld, Shannon Jackson, Caroline A. M. Klopper-Tol, Marieke J. H. A. Kruip, Britta Laros-van Gorkom, Christoph Male, Laurens Nieuwenhuizen, Susan Shapiro, Karin Fijnvandraat, Michiel Copens
Summary: This study investigated the discrepancy between one-stage and chromogenic assays of coagulation factor activity in moderate and mild hemophilia A and B patients. The results showed that only a small number of patients exhibited a discrepancy between the two assays, and this discrepancy was largely determined by laboratory variables.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Oncology
Marie Solvay, Pauline Holfelder, Simon Klaessens, Luc Pilotte, Vincent Stroobant, Juliette Lamy, Stefan Naulaerts, Quentin Spillier, Raphael Frederick, Etienne De Plaen, Christine Sers, Christiane A. Opitz, Benoit J. van den Eynde, Jingjing Zhu
Summary: This study aimed to clarify the link between IDO1/TDO expression, AHR pathway activation, and immune suppression. The results showed that tryptophan deprivation sensitizes the AHR pathway, leading to increased Treg differentiation and immune suppression.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Hematology
Takuji Yoshimura, Shoko Furukawa, Akihisa Oda, Tomoko Matsumoto, Kana Sasai, Midori Shima, Keiji Nogami
Summary: This study retrospectively examined the immune changes in 14 patients with hemophilia A during hemostatic, replacement, and immune-tolerance induction therapies. The findings revealed a change in humoral immunity with an increase in IgG4 and a decrease in IgG1 in some patients with high antibody titers. Additionally, high titers of antibodies against the A2-a2 domain were observed in some patients, but this did not necessarily correlate with immune-tolerance induction therapy failure.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Brandon Tse, Rosane Nisenbaum, Georgina Floros, Aziz Jiwajee, Jerome Teitel, Michelle Sholzberg
Summary: Continuous factor VIII (FVIII) or factor IX (FIX) infusions are commonly used for patients with hemophilia A (HA) or B (HB) undergoing surgery. This study found differences in initial recovery and subsequent FIX and FVIII levels, as well as clinical outcomes, among HB and HA patients receiving perioperative continuous infusion (CI) of recombinant FVIII and FIX concentrates. HB patients had higher initial bolus dose and longer length of hospital stay, suggesting a need for a higher CI rate for adequate surgical hemostatic coverage.
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
(2023)
Article
Hematology
Ricardo Mesquita Camelo, Maise Moreira Dias, Camila Caram-Deelder, Samantha Gouw, Laura Peixoto de Magalhaes, Luciana Werneck Zuccherato, Leticia Lemos Jardim, Andrea Goncalves de Oliveira, Rosangela de Albuquerque Ribeiro, Vivian Karla Brognoli Franco, Maria do Rosario Ferraz Roberti, Fabia Michelle Rodrigues de Araujo Callado, Leina Yukari Etto, Maria Aline Ferreira de Cerqueira, Monica Hermida Cerqueira, Claudia Santos Lorenzato, Ieda Solange de Souza, Edvis Santos Soares Serafim, Andrea Aparecida Garcia, Tania Hissa Anegawa, Daniele Campos Fontes Neves, Doralice Marvulle Tan, Johanna van der Bom, Suely Meireles Rezende
Summary: The aim of this study was to evaluate the association between the time elapsed between inhibitor detection and start of immune tolerance induction (ITI) and the ITI outcome in a large cohort of severe patients with hemophilia A and high-responding inhibitors (PwHA-HRi). The results showed that delayed ITI start is not associated with ITI failure in PwHA-HRi, suggesting that ITI should be offered regardless of the time elapsed between inhibitor detection and ITI start.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Joseph S. Gish, Lexi Jarvis, Kenneth C. Childers, Shaun C. Peters, Connor S. Garrels, Ian W. Smith, H. Trent Spencer, Christopher B. Doering, Pete Lollar, P. Clint Spiegel
Summary: The study reveals the structure of a therapeutically active fVIII construct complexed with an anti-C1 domain inhibitor, shedding light on the interaction between the antibody and fVIII, which may lead to the development of more effective and safe fVIII replacement therapies.
Article
Hematology
Weiqing Jing, Christina K. Baumgartner, Feng Xue, Jocelyn A. Schroeder, Qizhen Shi
Summary: In this study, we found that pre-existing inhibitors can lead to the loss of platelet-FVIII expression, and this loss is mediated by cytotoxic CD8 T cells. This finding is crucial for the treatment of hemophilia A patients with inhibitors.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Medicine, Research & Experimental
Hiromitsu Asashima, Dongjoo Kim, Kaicheng Wang, Nikhil Lele, Nicholas C. Buitrago-Pocasangre, Rachel Lutz, Isabella Cruz, Khadir Raddassi, William E. Ruff, Michael K. Racke, JoDell E. Wilson, Tara S. Givens, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Steven H. Kleinstein, Ruth R. Montgomery, Albert C. Shaw, Fangyong Li, Rong Fan, David A. Hafler, Mary M. Tomayko, Erin E. Longbrake
Summary: Repeated vaccination can enhance immune responses for some individuals with B cell depletion. While most patients did not show an increase in antibodies after the third dose of vaccine, a small subset of patients were still able to produce spike-specific antibodies, which persisted 6 months after vaccination.
Article
Hematology
Lynn Malec, An Van Damme, Anthony K. C. Chan, Mariya Spasova, Nisha Jain, Charlotte Sensinger, Jennifer Dumont, Stefan Lethagen, Manuel Carcao, Flora Peyvandi
Summary: Inhibitor development remains a major challenge in factor VIII replacement therapy. The verITI-8 study evaluated the use of a recombinant FVIII Fc fusion protein (rFVIIIFc) for immune tolerance induction in males with severe hemophilia A and high-titer inhibitors. The study showed that rFVIIIFc achieved tolerization in a significant number of patients within a short time period, and adverse events were generally well tolerated.
Article
Hematology
Connie M. Arthur, Patricia E. Zerra, Sooncheon Shin, Jianmei Wang, Xeuzheng Song, Christopher B. Doering, Pete Lollar, Shannon Meeks, Sean R. Stowell
Summary: Recombinant factor VIII (FVIII) products are crucial for the treatment of hemophilia A, but the development of antibodies against FVIII can limit its effectiveness. This study shows that the source of the recombinant FVIII product can influence the development of antibodies, with BHK-derived products displaying greater immunogenicity. The higher levels of nonhuman carbohydrate alpha Gal on BHK-derived FVIII suggest that it may contribute to the formation of anti-FVIII antibodies.
Article
Hematology
Kuniyoshi Mizumachi, Yuto Nakajima, Naruto Shimonishi, Shoko Furukawa, Kenichi Ogiwara, Masahiro Takeyama, Keiji Nogami
Summary: Hybrid FVIII proteins containing porcine FVIII A2 and/or C2 domain(s) can avoid neutralization and may support effective therapy in patients with congenital haemophilia A and inhibitor antibodies.
Article
Hematology
Albain Chansavang, Aurelien Philippe, Ines Bozinovic, Khalil Ben Hadj Ali, David Smadja, Dominique Helley, Luc Darnige, Laetitia Mauge
Summary: This study evaluated the performance of a commercial ELISA method for detecting anti-FVIII IgG in patients with acquired hemophilia A. The results showed 100% sensitivity and specificity, and correlated with the traditional Bethesda assay. These data suggest the potential use of this method for both diagnosis and follow-up of AHA patients.
ANNALS OF HEMATOLOGY
(2022)
Article
Cell Biology
Chao Lien Liu, Meghan J. Lyle, Simon C. Shin, Carol H. Miao
CELLULAR IMMUNOLOGY
(2016)
Article
Biochemistry & Molecular Biology
T. L. Mao, K. F. Fan, C. L. Liu
Article
Hematology
C. L. Liu, P. Ye, J. Lin, D. Djukovic, C. H. Miao
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2014)
Article
Biotechnology & Applied Microbiology
Chao-Lien Liu, Peiqing Ye, Benjamin C. Yen, Carol H. Miao
Article
Oncology
Chao Lien Liu, Hung Wei Pan, Pao Ling Torng, Ming Huei Fan, Tsui Lien Mao
Article
Oncology
Yuan-Hsi Wang, Chao-Lien Liu, Wan-Chun Chiu, Yuh-Ching Twu, Yi-Jen Liao
Article
Pharmacology & Pharmacy
Yuan-Hsi Wang, Fat-Moon Suk, Chao-Lien Liu, Tzu-Lang Chen, Yuh-Ching Twu, Ming-Hua Hsu, Yi-Jen Liao
FRONTIERS IN PHARMACOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Chao Lien Liu, Ying Jen Chen, Ming Huei Fan, Yi Jen Liao, Tsui Lien Mao
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biology
Ying Jen Chen, Yi Jen Liao, Van Thi Ngoc Tram, Chung Hao Lin, Kuo Chen Liao, Chao Lien Liu
Review
Biochemistry & Molecular Biology
Chao-Lien Liu, Ray-Hwang Yuan, Tsui-Lien Mao
Summary: Molecular markers play a crucial role in predicting aggressiveness, prognosis, recurrence, and novel therapeutic targets in the management of epithelial ovarian cancer (EOC). Biomarkers derived from genomic/epigenomic alterations enable targeted treatment of affected signaling pathways, thereby improving the effectiveness of traditional treatments.
Article
Biochemistry & Molecular Biology
Tsui-Lien Mao, Ming-Huei Fan, Nhlanhla Dlamini, Chao-Lien Liu
Summary: The upregulation of MALAT1 in epithelial ovarian cancer is associated with activation of tumor-related signaling pathways, influencing apoptosis, inflammation, proliferation, and invasion processes in cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Chao Lien Liu, Meghan J. Lyle, Simon C. Shin, Carol H. Miao
Article
Biochemistry & Molecular Biology
Chao-Lien Liu, I-Shing Yu, Hung-Wei Pan, Shu-Wha Lin, Hey-Chi Hsu
JOURNAL OF BIOLOGICAL CHEMISTRY
(2007)
Article
Oncology
Chao-Lien Liu, Jim Jinn-Chyuan Sheu, Hsuan-Ping Lin, Yung-Ming Jeng, Cherry Yin-Yi Chang, Chih-Mei Chen, Jack Cheng, Tsui-Lien Mao
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
(2019)