Article
Hematology
Jasmine Ito, Wallace Hunter Baldwin, Courtney Cox, John F. Healey, Ernest T. Parker, Emily R. Legan, Renhao Li, Surinder Gill, Glaivy Batsuli
Summary: This study evaluated the impact of site-specific N-linked glycan removal on FVIII properties, cell internalization, and antibody responses. The results showed that modifying FVIII N-linked glycans reduced endocytosis by dendritic cells and binding of specific antibodies, but did not significantly affect inhibitor formation in hemophilia A mice.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
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)
Review
Hematology
Kenneth C. Childers, Shaun C. Peters, Paul Clint Spiegel
Summary: Advances in structural studies of blood coagulation factor VIII (FVIII) have provided important insights into the biochemical properties of FVIII, particularly the mutations associated with hemophilia A. By analyzing the atomic details of FVIII structures, researchers can design recombinant FVIII with improved circulatory half-life. Recent structural studies of FVIII bound to inhibitory antibodies have also enhanced our understanding of FVIII binding to activated platelet membranes and the formation of the intrinsic tenase complex.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
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
Hematology
Larissa Maira Moura de Oliveira, Leticia Lemos Jardim, Marcio Antonio Portugal Santana, Monica Hermida Cerqueira, Claudia Santos Lorenzato, Vivian Karla Brognoli Franco, Luciana Werneck Zuccherato, Suely Meireles Rezende, Daniel Goncalves Chaves
Summary: This study investigated the effect of initial FVIII infusions on immunological biomarkers in previously untreated patients with Hemophilia A. It was found that patients who developed inhibitors had higher levels of antibodies, cytokines, and chemokines compared to those without inhibitors, indicating a mixed cytokine profile. Exposure to FVIII triggers an inflammatory response mediated by IL-6 and CXCL8 in patients with HA who developed inhibitors, while the immune system of all HA patients is stimulated after infusions of FVIII regardless of inhibitor status.
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
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
Karina Winterling, William D. Martin, Anne S. De Groot, Jens Daufenbach, Steffen Kistner, Joerg Schuettrumpf
Summary: By modifying the structure of the FVIII molecule, a partially deimmunized FVIII was successfully developed, demonstrating full functionality and lower immunogenicity in in vitro testing. This approach holds promise for reducing inhibitor risk in patients with hemophilia A.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Richard A. Marlar, Jana N. Gausman, Marian A. Rollins-Raval
Summary: The management of hemophilia A has evolved significantly in recent years with the introduction of new and modified treatment products. Many standard factor VIII assays may not accurately measure all available products, leading to uncertainty in laboratories. This study evaluates various assay algorithms for optimal assessment of hemophilia A patients and treatment products, providing guidelines for laboratories to select cost-effective algorithms suitable for their clinical situation and resources.
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
(2022)
Article
Hematology
James R. Fuller, Kevin E. Knockenhauer, Nina C. Leksa, Robert T. Peters, Joseph D. Batchelor
Summary: The interaction between FVIII and VWF is crucial for hemostasis, and mutations affecting this interaction can lead to von Willebrand disease type 2N. Understanding the structural basis of this interaction is important for developing therapies for bleeding disorders like hemophilia A. The structure of the bioengineered FVIII molecule BIVV001 provides insights into the FVIII-VWF complex formation and sheds light on mutations associated with hemophilia A and VWD type 2N.
Article
Multidisciplinary Sciences
Morisada Hayakawa, Asuka Sakata, Hiroko Hayakawa, Hikari Matsumoto, Takafumi Hiramoto, Yuji Kashiwakura, Nemekhbayar Baatartsogt, Noriyoshi Fukushima, Yoichi Sakata, Katsue Suzuki-Inoue, Tsukasa Ohmori
Summary: The study found that in mice, FVIII is produced only from liver sinusoidal endothelial cells exhibiting high levels of CD31, CD146, Lyve1, CLEC-2, and negative for podoplanin expression.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Seema R. Patel, Taran S. Lundgren, Wallace Hunter Baldwin, Courtney Cox, Ernest T. Parker, John F. Healey, Ryan P. Jajosky, Patricia E. Zerra, Cassandra D. Josephson, Christopher B. Doering, Sean R. Stowell, Shannon L. Meeks
Summary: The immune response to factor VIII in patients with hemophilia A differs between individuals due to genetic factors, which may explain the variation in inhibitor formation. This study highlights the underappreciated immunological pathway of humoral immunity to factor VIII and lays the foundation for identifying biomarkers to develop tolerance against factor VIII.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medical Laboratory Technology
Armando Tripodi, Veena Chantarangkul, Cristina Novembrino, Erica Scalambrino, Massimo Boscolo-Anzoletti, Marigrazia Clerici, Federica Rossi, Flora Peyvandi
Summary: This study demonstrates that by making slight modifications to the OSA for FVIII, it can reliably measure the concentration of emicizumab and assist clinicians in managing patients on emicizumab. Additionally, the use of CA assay with bovine reagents can effectively measure the inhibitors to FVIII in patients receiving emicizumab treatment.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2021)
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
Cell Biology
Srinivasa Reddy Bonam, Camille Chauvin, Mano J. Mathew, Jagadeesh Bayry
Summary: This study identifies IFN-gamma as one of the factors that induce PD-L1 expression in human basophils and demonstrates the importance of IL-3 priming in IFN-gamma-induced PD-L1 expression.
Review
Multidisciplinary Sciences
Deepak Kumar, Jagadeesh Bayry, Nagendra R. Hegde
Summary: Interface with animals has played a major role in the occurrence of human diseases, including recent viral outbreaks like COVID-19. The zoonotic origin of the virus highlights the importance of collaboration among human and animal health professionals. Applying the One Health principles is crucial for better preparation for future zoonotic disease outbreaks and pandemics.
JOURNAL OF THE INDIAN INSTITUTE OF SCIENCE
(2022)
Article
Cell Biology
Xavier Charmetant, Chien-Chia Chen, Sarah Hamada, David Goncalves, Carole Saison, Maud Rabeyrin, Marion Rabant, Jean-Paul Duong van Huyen, Alice Koenig, Virginie Mathias, Thomas Barba, Florence Lacaille, Jerome le Pavec, Olivier Brugiere, Jean-Luc Taupin, Lara Chalabreysse, Jean-Francois Mornex, Lionel Couzi, Stephanie Graff-Dubois, Raphal Jeger-Madiot, Alexy Tran-Dinh, Pierre Mordant, Helena Paidassi, Thierry Defrance, Emmanuel Morelon, Lionel Badet, Antonino Nicoletti, Valerie Dubois, Olivier Thaunat
Summary: Generation of antibodies against donor-specific MHC antigens after transplantation requires help from recipient's T cells, but our study shows that CD3e knockout recipient mice lacking T cells can still generate antibodies due to the presence of donor CD4+ T cells within the graft. This inverted direct pathway may also be operant in patients after transplantation.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Alexy Tran-Dinh, Quentin Laurent, Guillaume Even, Sebastien Tanaka, Brice Lortat-Jacob, Yves Castier, Herve Mal, Jonathan Messika, Pierre Mordant, Antonino Nicoletti, Philippe Montravers, Giuseppina Caligiuri, Ian Morilla
Summary: The contribution of artificial intelligence in predicting the risk of acute cellular rejection after lung transplantation was evaluated by combining early plasma levels of sCD31 with recipient oxygen status and respiratory SOFA score. The study is significant for understanding the predictive mechanisms of ACR.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Srinivasa Reddy Bonam, Peter Paul Platenburg, Jagadeesh Bayry
Summary: In this study, the immunopotentiating mechanism of an oil-in-water emulsion-based vaccine adjuvant called LiteVax Adjuvant (LVA) was analyzed. The researchers investigated the effect of LVA and its components on the function of dendritic cells (DC), which play a crucial role in the immune response. They found that the component CMS significantly enhanced DC activation markers, cytokine secretion, and CD4(+) T cell responses. This study identified the unique role of CMS in LVA and proposed that LVA acts as a delivery system while CMS acts as an immunostimulatory agent.
FRONTIERS IN IMMUNOLOGY
(2023)
Letter
Hematology
Cedric Hermans, Jan Astermark, Manuela Carvalho, Gerry Dolan, Roseline d'Oiron, Pierre Fontana, Pal Andre Holme, Gili Kenet, Robert Klamroth, Maria Elisa Mancuso, Natascha Marquardt, Ramiro Nunez, Olga Katsarou, Ingrid Pabinger-Fasching, Gabriele Quintavalle, Ryan Rodgers, Paul van der Valk, Jerzy Windyga, Victor Jimenez Yuste, Irena Preloznik Zupan
Article
Hematology
Philippe de Mazancourt, Florence Quelin, Claire Flaujac, Emmanuelle de Raucourt, Benoit Guillet, Frederic Bauduer, Vincent Ernest, Philippe Beurrier, Aurelie Avril, Roseline d'Oiron, Christine Biron-Andreani, Sandrine Meunier, Yesim Dargaud
Summary: This study aimed to identify putative dominant-negative F11 variants. Through retrospective analysis of laboratory data from 170 patients with moderate/mild factor XI deficiencies, we identified carriers of previously reported dominant-negative variants, but their FXI activities did not match with the expected dominant-negative effect. We also found a set of patients carrying heterozygous variants, including novel ones, with FXI activities suggesting a dominant-negative effect, but for most of these variants, individuals with close to half normal FXI activity were identified, indicating an inconsistent dominant effect.
Editorial Material
Rheumatology
Chetan Sharma, Jagadeesh Bayry
Summary: The full understanding of post-COVID-19 autoimmune diseases and their prevalence is limited. However, two large-scale studies have found a significant increase in the risk of developing various new-onset autoimmune diseases linked to SARS-CoV-2 infection.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Review
Pharmacology & Pharmacy
Sruthi Vijaya Retnakumar, Camille Chauvin, Jagadeesh Bayry
Summary: T cell exhaustion is a major obstacle in mounting immune responses against chronic infections and cancers. Immune checkpoint (ICP) molecules, especially PD-1, contribute to T cell dysfunction. Blocking PD-1 can reverse T cell exhaustion and stimulate the impaired immune system. The interaction between vaccine responses and ICP therapy needs further exploration.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Immunology
Carole El Hachem, Pierre Marschall, Pierre Hener, Anupama Karnam, Srinivasa Reddy Bonam, Pierre Meyer, Eric Flatter, Marie-Christine Birling, Jagadeesh Bayry, Mei Li
Summary: This study investigates the mechanisms of basophil recruitment to allergic skin using a mouse model of allergic contact dermatitis. It demonstrates that IL-3 produced by T cells mediates the extravasation of basophils by activating the expression of ALDH1A2, which is responsible for the production of retinoic acid. IL-3 also induces the expression of integrins involved in basophil extravasation.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Allergy
Jagadeesh Bayry, Eisha A. Ahmed, Diana Toscano-Rivero, Nicholas Vonniessen, Genevieve Genest, Casey G. Cohen, Marieme Dembele, Srini Kaveri, Bruce D. Mazer
Summary: Intravenous immunoglobulin (IVIG) plays a crucial role in the treatment of humoral immune deficiencies and inflammatory disorders. While targeted therapies are emerging, the multifunctionality of IVIG as both an effector and regulatory molecule is noteworthy. This article explores the mechanism of action of IVIG in various resistant conditions and highlights mechanistic studies that shed light on its effects on both innate and adaptive immune responses.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2023)
Editorial Material
Immunology
Sruthi Vijaya Retnakumar, Srinivasa Reddy Bonam, Haitao Hu, Jagadeesh Bayry
Article
Immunology
Nabarun Chandra Das, Pritha Chakraborty, Jagadeesh Bayry, Suprabhat Mukherjee
Summary: Mutation(s) in the spike protein is a major characteristic trait of newly emerged SARS-CoV-2 variants. Omicron, the latest variant, is highly transmissible and can escape host immunity. The study found that adintivimab, beludivimab, and regadanivimab are the most potent monoclonal antibodies in neutralizing Omicron variants.
Editorial Material
Cell Biology
Camille Chauvin, Sruthi Vijaya Retnakumar, Jagadeesh Bayry
Summary: Severe obesity speeds up the decline of neutralizing antibodies to COVID-19 vaccines, increasing the risk of hospitalization from breakthrough SARS-CoV-2 infections. These findings have implications for vaccination policies for SARS-CoV-2 variants and other infectious diseases like influenza in the obese population.
CELL REPORTS MEDICINE
(2023)
Article
Multidisciplinary Sciences
Camille Chauvin, Laurine Levillayer, Mathilde Roumier, Hubert Nielly, Claude Roth, Anupama Karnam, Srinivasa Reddy Bonam, Anne Bourgarit, Clement Dubost, Aurore Bousquet, Sebastien Le Burel, Raphaele Mestiri, Daminen Sene, Joris Galland, Marc Vasse, Matthieu Groh, Mathilde Le Marchand, Camille Vassord-Dang, Jean-Francois Gautier, Pham-Thi Nhan, Christian Verny, Bruno Pitaro, Cyril Planchais, Hugo Mouquet, Richard Paul, Etienne Simon-Loriere, Jagadeesh Bayry, Laurent Gilardin, Anavaj Sakuntabhai
Summary: Although tocilizumab treatment has shown efficacy in severe COVID-19 patients, its short-term use does not affect B cell sub-populations and cross-neutralization of SARS-CoV-2 variants in convalescent COVID-19 patients. The study found that SARS-CoV-2-specific IgG1 titers were dependent on disease severity rather than tocilizumab treatment. Both treated and non-treated patients had strong neutralizing activity against ancestral and several variants of SARS-CoV-2, but weaker activity against the Gamma and Omicron variants. Overall, tocilizumab therapy did not modify the robustness of cell and IgG responses to Spike antigens.
