Abstract:
PURPOSE OF REVIEW:The review describes recent advances in our understanding of mechanisms leading to development of neutralizing antibodies following factor VIII (FVIII) replacement therapy for hemophilia A. Novel interventions with translational potential to lessen the incidence of these deleterious immune responses are discussed. RECENT FINDINGS:Genetic and environmental risk factors for inhibitor development, and cellular mechanisms leading to antibody production versus immune tolerance to FVIII, are increasingly coming into focus. Human and animal model studies are identifying T-cell and B-cell epitopes in FVIII and characterizing the presentation of naturally processed FVIII peptides on antigen-presenting cells (APCs). Novel methods to promote immune tolerance include decreasing FVIII uptake by APCs, modifying co-stimulatory pathways, inducing regulatory T-cell production, and presenting FVIII antigen to immature dendritic cells in a tolerance-promoting manner. A complementary approach to reduce inhibitor incidence is the design of less immunogenic FVIII proteins through epitope modification. SUMMARY:Studies of FVIII immunogenicity are revealing mechanisms of anti-FVIII immune responses, suggesting new approaches to reduce the incidence of inhibitors. Rational design of FVIII variants is producing less immunogenic proteins targeted to specific patient sub-populations. Future therapies will likely involve administration of less immunogenic FVIII proteins under conditions that promote immune tolerance.
journal_name
Curr Opin Hematoljournal_title
Current opinion in hematologyauthors
Pratt KPdoi
10.1097/MOH.0b013e328356ed37subject
Has Abstractpub_date
2012-09-01 00:00:00pages
399-405issue
5eissn
1065-6251issn
1531-7048journal_volume
19pub_type
杂志文章,评审abstract:PURPOSE OF REVIEW:Endothelial cells dysfunctions are crucial determinants of several human diseases. We review here the most recent reports on endothelial cell defects in cerebral cavernous malformations (CCMs), particularly focusing on adherens junctions. CCM is a vascular disease that affects specifically the venous ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000338
更新日期:2017-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Hematopoietic stem cell (HSC) transplantation is the most powerful treatment modality for a variety of hematological disorders. Successful hematopoietic recovery after transplantation depends on optimal homing of HSCs to the bone marrow and subsequent lodging in the HSC niche. The molecular mechanisms...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32834760e5
更新日期:2011-07-01 00:00:00
abstract::Matching for human leukocyte antigen (HLA) loci is the most crucial factor in the selection of bone marrow donors. The techniques utilized to assign HLA type have evolved significantly since the application of polymerase chain reaction-based methodologies. A significant challenge for DNA typing methodologies is to be ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199811000-00012
更新日期:1998-11-01 00:00:00
abstract:PURPOSE OF REVIEW:In addition to its essential role in baseline erythropoiesis, the hormone erythropoietin drives the erythropoietic response to hypoxic stress. A mechanistic understanding of stress erythropoiesis would benefit multiple clinical settings, and may aid in understanding leukemogenesis. RECENT FINDINGS:Th...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3280de2bf1
更新日期:2007-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Although the zebrafish has been established as a research tool over the past two to three decades, in hematology it has primarily been used to investigate areas distinct from coagulation. The advantages of this vertebrate model include high fecundity, rapid and external development, and conservation o...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000075
更新日期:2014-09-01 00:00:00
abstract::Following on the heels of multiple failed clinical trials of adjunctive therapeutic agents in sepsis, the positive outcome of a recent phase III study using activated protein C (APC) has led to a renewed optimism in targeted biotherapies for this syndrome. A growing body of data (both preclinical and clinical) suggest...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200209000-00005
更新日期:2002-09-01 00:00:00
abstract:PURPOSE OF REVIEW:Gfi-1, originally identified as a transcriptional repressor in lymphoid cells, is now recognized to have essential, independent functions in neutrophil maturation and hematopoietic stem cell biology. Here we review recent studies pertaining to Gfi-1 and its cell context specific functions in hematopoi...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000190111.85284.8f
更新日期:2006-01-01 00:00:00
abstract:PURPOSE OF REVIEW:Chronic inflammation and disordered lipid metabolism represent hallmarks of atherosclerosis. Considerable evidence has accumulated to suggest that innate immune defense mechanisms might interact with proinflammatory pathways and exacerbate or perhaps even initiate development of arterial plaques. Unti...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000219662.88409.7c
更新日期:2006-05-01 00:00:00
abstract::Multiple myeloma is the second most common hematologic malignancy, with approximately 15,000 new cases each year in the United States. Our understanding of the pathophysiology underlying myeloma continues to expand, but the cause of this plasma cell dyscrasia remains unclear. Though controversy remains regarding a pos...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200007000-00007
更新日期:2000-07-01 00:00:00
abstract:PURPOSE OF REVIEW:The role of a patent foramen ovale (PFO) as a risk factor for ischemic stroke has been established in recent years. However, the best therapeutic option to prevent recurrent events is still controversial, with antithrombotic treatment or transcatheter PFO closure being favored by different clinicians....
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32832d47dd
更新日期:2009-09-01 00:00:00
abstract::Endothelial cell invasion is an essential event during angiogenesis (the formation of new blood vessels). This process involves the degradation of the extracellular matrix, the basement membrane, and interstitial stroma, and is governed by the activation of matrix metalloproteinases. However, the contribution of matri...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200303000-00007
更新日期:2003-03-01 00:00:00
abstract:PURPOSE OF REVIEW:The increasing use of high throughput sequencing and genomic analysis has facilitated the discovery of new causes of inherited platelet disorders. Studies of these disorders and their respective mouse models have been central to understanding their biology, and also in revealing new aspects of platele...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000525
更新日期:2019-09-01 00:00:00
abstract:PURPOSE OF REVIEW:Chronic idiopathic and severe congenital neutropenias are rare disorders for which recent discoveries have highlighted mechanisms and consequences. RECENT FINDINGS:An inflammatory bone marrow milieu has been shown to be a major contributor to the pathophysiology of chronic idiopathic neutropenia. Act...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3282f172d3
更新日期:2008-01-01 00:00:00
abstract:PURPOSE OF REVIEW:To highlight mechanisms that regulate the balance between latent and active von Willebrand factor (VWF), and describe pathological conditions leading to increased levels of active VWF. RECENT FINDINGS:Levels of circulating active VWF are increased in von Willebrand disease type 2B, HELLP syndrome, ma...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3280dce531
更新日期:2007-05-01 00:00:00
abstract:PURPOSE OF REVIEW:Lymphocyte trafficking is regulated by adhesion molecules mediating the initial shear-resistant binding of circulating cells to target tissue endothelium (Step 1). This review focuses on the current and emerging perspectives of the biology of these 'homing receptors.' RECENT FINDINGS:The conventional...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/01.moh.0000177827.78280.79
更新日期:2005-11-01 00:00:00
abstract:PURPOSE OF REVIEW:This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeti...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000401
更新日期:2018-03-01 00:00:00
abstract::Leukocytes use an array of antimicrobial peptides and proteins to help them destroy invading microorganisms. These endogenous antibiotic molecules are remarkable for their structural variety, rapid evolutionary divergence, intraspecies variation, and complex yet subtle interactions with their targets. This arsenal has...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199704010-00009
更新日期:1997-01-01 00:00:00
abstract::Modern molecular technology helped identify more than 10 protein tyrosine kinases related to myeloid malignancies, which allowed the development of small molecule inhibitors targeting deregulated protein tyrosine kinase activity. Protein tyrosine kinase deregulation can occur as a consequence of fusion gene formation ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200301000-00007
更新日期:2003-01-01 00:00:00
abstract::Contrast venography remains the gold standard for the diagnosis of deep-vein thrombosis (DVT). However, an ongoing interest exists in developing safe diagnostic strategies that are less invasive, less expensive, widely and readily available, and more acceptable to patients than venography. For patients with symptoms s...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199909000-00001
更新日期:1999-09-01 00:00:00
abstract:PURPOSE OF REVIEW:Platelet microparticles were identified more than 40 years ago and are the most abundant circulating microparticle subtype. Yet fundamental questions about their formation and role in human disease are just beginning to be understood at the cellular and molecular level. This review will address mechan...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32833e77ee
更新日期:2010-11-01 00:00:00
abstract:PURPOSE OF REVIEW:The present review elucidates the potentials of recombinant blood group proteins (BGPs) for red blood cell (RBC) antibody detection and identification in pretransfusion testing and the achievements in this field so far. RECENT FINDINGS:Many BGPs have been eukaryotically and prokaryotically expressed ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e3283319a06
更新日期:2009-11-01 00:00:00
abstract:PURPOSE OF REVIEW:The identification of regulatory T cells (Tregs) as regulators of immunological self-tolerance has stimulated tremendous interest in the field. Over the past 12 months, new studies have added greatly to our understanding of the role of Tregs in autoimmune disease, details of which are presented here. ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0b013e32832a9a01
更新日期:2009-07-01 00:00:00
abstract:PURPOSE OF REVIEW:The presence of the Philadelphia chromosome causing the fusion between BCR to ABL1 in B cell precursor acute lymphoblastic leukemias (ALLs) was associated with a particularly bad prognosis, which has been markedly improved with the addition of imatinib to chemotherapy. Recent genomic studies have lead...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000050
更新日期:2014-07-01 00:00:00
abstract::This overview concentrates on familial and congenital polycythemias in the context of other polycythemic disorders, with emphasis on those with established molecular lesions. Recent advances in the regulation of erythropoiesis, as they may relate to polycythemic states, are discussed as a background for those well-def...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199903000-00008
更新日期:1999-03-01 00:00:00
abstract::Human immunodeficiency virus infection causes multilineage hematopoietic defects. Defects in the production and function of CD4+ helper cells have been the focus of the majority of HIV research, but anemia, neutropenia, and thrombocytopenia are significant clinical problems as well. Bone marrow suppression is the dose...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-199502030-00012
更新日期:1995-05-01 00:00:00
abstract::Recent advances in our understanding of hypereosinophilia have related particularly to the definition of criteria for distinguishing between eosinophilic leukemia and the 'idiopathic' hypereosinophilic syndromes. In this article, leukemogenic mechanisms have been identified in a number of subtypes of eosinophilic leuk...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200001000-00005
更新日期:2000-01-01 00:00:00
abstract::Anemia is a common disorder in patients with cancer and can be caused by the disease itself or by cancer-related therapy. The cardinal symptom of anemia, fatigue, is the most commonly reported symptom in patients with cancer and has profound effects on patient well-being and quality of life. Until recently, blood tran...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200205000-00010
更新日期:2002-05-01 00:00:00
abstract::Allogeneic barriers to transfusion are caused by differences between those portions of the donor and recipient genomes that define the antigenicity and immune response to the transfused cells. Historically, a blood group antigen was identified when an immune response (alloantibody) was detected by hemagglutination in ...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200203000-00012
更新日期:2002-03-01 00:00:00
abstract::D-dimer, a breakdown product of cross-linked fibrin has been extensively evaluated as a diagnostic test for acute venous thromboembolism. Rapid, highly sensitive D-dimer assays are now available that are suitable for testing in the emergency setting. Preliminary studies suggest that when using a highly sensitive D-dim...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/00062752-200009000-00007
更新日期:2000-09-01 00:00:00
abstract::: Hematopoietic stem cells (HSCs) are a unique population of cells with the remarkable ability to replenish themselves through self-renewal and to give rise to differentiated cell lineages. Though having been discovered more than 50 years ago, and having been widely used in bone marrow transplantation to treat blood d...
journal_title:Current opinion in hematology
pub_type: 杂志文章,评审
doi:10.1097/MOH.0000000000000506
更新日期:2019-07-01 00:00:00