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Factor VIII antibody

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https://www.readbyqxmd.com/read/28285015/tnf%C3%AE-contributes-to-diabetes-impaired-angiogenesis-in-fracture-healing
#1
Jason C Lim, Kang I Ko, Marcelo Mattos, Miao Fang, Citong Zhang, Daniel Feinberg, Hisham Sindi, Shuai Li, Jazia Alblowi, Rayyan A Kayal, Thomas A Einhorn, Louis Gerstenfeld, Dana Graves
Diabetes increases the likelihood of fracture, interferes with fracture healing and impairs angiogenesis. The latter may be significant due to the critical nature of angiogenesis in fracture healing. Although it is known that diabetes interferes with angiogenesis the mechanisms remain poorly defined. We examined fracture healing in normoglycemic and streptozotocin-induced diabetic mice and quantified the degree of angiogenesis with antibodies to three different vascular markers, CD34, CD31 and Factor VIII. The role of diabetes-enhanced inflammation was investigated by treatment of the TNFα-specific inhibitor, pegsunercept starting 10days after induction of fractures...
March 8, 2017: Bone
https://www.readbyqxmd.com/read/28262242/an-extra-x-does-not-prevent-acquired-hemophilia-pregnancy-associated-acquired-hemophilia-a
#2
Assaf A Barg, Tami Livnat, Gili Kenet
Acquired hemophilia A (AHA) is a severe bleeding disorder caused by autoantibodies against clotting factor VIII (FVIII). With an estimated annual incidence of 1.3 to 1.5 per million, AHA is a rare disease. An extremely rare form of AHA has been described among women in the peripartum period, and may present with peripartum hemorrhage. Notably, although hemorrhagic symptoms commonly present 1-4 months around delivery, they may occur up to 1 year after parturition. When caring for a mother with AHA it is important to note that Factor VIII inhibitor may be transferred via the placenta from the mother to the fetus...
March 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28258054/thrombophilia-risk-is-not-increased-in-children-after-perinatal-stroke
#3
Colleen Curtis, Aleksandra Mineyko, Patricia Massicotte, Michael Leaker, Xiu Yan Jiang, Amalia Floer, Adam Kirton
Perinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable but mechanisms are poorly understood. Evidence suggests possible associations between arterial perinatal stroke and prothrombotic disorders but population-based, controlled, disease-specific studies are limited. Understanding thrombophilia in perinatal stroke informs pathogenesis models and clinical management. We conducted a population-based, prospective, case-control study to determine the association of specific perinatal stroke diseases with known thrombophilias...
March 3, 2017: Blood
https://www.readbyqxmd.com/read/28164173/tgf-%C3%AE-1-along-with-other-platelet-contents-augments-treg-cells-to-suppress-anti-fviii-immune-responses-in-hemophilia-a-mice
#4
Dipica Haribhai, Xiaofeng Luo, Juan Chen, Shuang Jia, Linzheng Shi, Jocelyn A Schroeder, Hartmut Weiler, Richard H Aster, Martin J Hessner, Jianda Hu, Calvin B Williams, Qizhen Shi
Platelets are a rich source of many cytokines and chemokines including transforming growth factor β 1 (TGF-β1). TGF-β1 is required to convert conventional CD4(+) T (Tconv) cells into induced regulatory T (iTreg) cells that express the transcription factor Foxp3. Whether platelet contents will affect Treg cell properties has not been explored. In this study, we show that unfractionated platelet lysates (pltLys) containing TGF-β1 efficiently induced Foxp3 expression in Tconv cells. The common Treg cell surface phenotype and in vitro suppressive activity of unfractionated pltLys-iTreg cells were similar to those of iTreg cells generated using purified TGF-β1 (purTGFβ-iTreg) cells...
December 13, 2016: Blood Adv
https://www.readbyqxmd.com/read/28157676/inhibitory-antibodies-against-factor-viii-c1-domain
#5
Gary E Gilbert
No abstract text is available yet for this article.
October 20, 2016: Blood
https://www.readbyqxmd.com/read/28135035/fibrinolysis-inhibitors-in-plaque-stability-a-morphological-association-pai-1-and-tafi-in-advanced-carotid-plaque
#6
A-C Jönsson Rylander, A Lindgren, J Deinum, G M L Bergström, G Böttcher, I Kalies, K Wåhlander
BACKGROUND: Fibrinolysis plays an important role in destabilization of atherosclerotic plaques and is tightly regulated by specific inhibitors. OBJECTIVE: The fibrinolysis inhibitors PAI-1 and TAFI were quantified and described in the morphological context of advanced carotid plaques (AHA VI-VIII) to elucidate their role in plaque stability. METHODS: Immunohistochemistry in serial sections along the longitudinal axis of endarterectomies from patients with symptomatic carotid stenosis (n=19) were studied using an antibody specific for free PAI-1 (I205), an antibody with high affinity for TAFI/TAFIa (CP17) and established antibodies for SMC (α-actin), endothelial cells (Von Willebrandt Factor, VWF), macrophages (CD68) and platelets (CD42)...
January 30, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28087107/establishment-of-the-2nd-korean-national-biological-reference-standard-for-blood-coagulation-factor-viii-c-concentrate
#7
Naery Lee, Ji Suk Seo, Jae Ok Kim, Sang Ja Ban
Since the 1st Korean national biological reference standard for factor (F)VIII concentrate, established in 2001, has shown declining potency, we conducted this study to replace this standard with a 2nd Korean national biological reference standard for blood coagulation FVIII concentrate. The candidate materials for the 2nd standard were prepared in 8000 vials with 10 IU/ml of target potency, according to the approved manufacturing process of blood coagulation Factor VIII:C Monoclonal Antibody-purified, Freeze-dried Human Blood Coagulation Factor VIII:C...
January 10, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28064157/fviii-specific-human-chimeric-antigen-receptor-t-regulatory-cells-suppress-t-and-b-cell-responses-to-fviii
#8
Jeongheon Yoon, Anja Schmidt, Ai-Hong Zhang, Christoph Königs, Yong Chan Kim, David W Scott
Replacement therapy with factor VIII (FVIII) is used in patients with hemophilia A for treatment of bleeding episodes or for prophylaxis. A common and serious problem with this therapy is the patient's immune response to FVIII, because of a lack of tolerance, leading to the formation of inhibitory antibodies. Development of tolerogenic therapies, other than standard immune tolerance induction (ITI), is an unmet goal. We previously generated engineered antigen-specific regulatory T cells (Tregs), created by transduction of a recombinant T-cell receptor (TCR) isolated from a hemophilia A subject's T-cell clone...
January 12, 2017: Blood
https://www.readbyqxmd.com/read/28063233/establishment-of-a-new-conditionally-immortalized-human-skeletal-muscle-microvascular-endothelial-cell-line
#9
Hironori Sano, Yasuteru Sano, Eri Ishiguchi, Fumitaka Shimizu, Masatoshi Omoto, Toshihiko Maeda, Hideaki Nishihara, Yukio Takeshita, Shiori Takahashi, Mariko Oishi, Takashi Kanda
In skeletal muscle, the capillaries have tight junctions (TJs) that are structurally similar to those in the blood-brain barrier (BBB) and blood-nerve barrier (BNB). Although many findings have been clarified in the territory of BBB and BNB, few have so far examined the TJs of capillaries in the skeletal muscle. In addition, no in vitro human skeletal muscle microvasculature models have been reported thus far. We newly established a new human skeletal muscle microvascular endothelial cell (HSMMEC) line. HSMMECs were isolated from human skeletal muscle and were infected with retroviruses harboring temperature-sensitive SV40 T antigen and telomerase genes...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28063132/evaluation-of-role-of-fv-fviii-and-aplas-in-the-pathogenesis-of-apcr-in-fv-leiden-negative-dvt-patients-a-study-in-india
#10
Amit Sharma, Kanwaljeet Singh, Arijit Biswas, Ravi Ranjan, Kamal Kishor, Ravi Kumar, Hareram Pandey, Vineet Kumar Kamal, Renu Saxena
Resistance to APC (APCR) is a very important cause of thrombophilia and most frequently caused by the Leiden mutation. APCR is also seen in the absence of FV Leiden and associated with elevated levels of factor V (FV), factor VIII (FVIII) and antiphospholipid antibodies (APLAs). The aim of this prospective case control study was to find out the frequency and role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative deep vein thrombosis (DVT) patients in India. A total 30 APCR positive and FV Leiden negative patients with DVT and similar number of age and sex matched healthy controls were recruited...
January 6, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28056565/characterization-of-aav-mediated-human-factor-viii-gene-therapy-in-hemophilia-a-mice
#11
Jenny A Greig, Qiang Wang, Amanda L Reicherter, Shu-Jen Chen, Alexandra L Hanlon, Christopher H Tipper, K Reed Clark, Samuel Wadsworth, Lili Wang, James M Wilson
Adeno-associated viral (AAV) vectors are promising vehicles for hemophilia gene therapy, with favorable clinical trial data seen in the treatment of hemophilia B. In an effort to optimize the expression of human coagulation factor VIII (hFVIII) for the treatment of hemophilia A, we performed an extensive study with numerous combinations of liver-specific promoter and enhancer elements with a codon-optimized hFVIII transgene. After generating 42 variants of three reduced-size promoters and three small enhancers, transgene cassettes were packaged within a single AAV capsid, AAVrh10, to eliminate performance differences due to the capsid type...
January 5, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28036020/bispecific-antibodies-as-a-development-platform-for-new-concepts-and-treatment-strategies
#12
REVIEW
Fa Yang, Weihong Wen, Weijun Qin
With the development of molecular cloning technology and the deep understanding of antibody engineering, there are diverse bispecific antibody formats from which to choose to pursue the optimal biological activity and clinical purpose. The single-chain-based bispecific antibodies usually bridge tumor cells with immune cells and form an immunological synapse because of their relatively small size. Bispecific antibodies in the IgG format include asymmetric bispecific antibodies and homodimerized bispecific antibodies, all of which have an extended blood half-life and their own crystalline fragment (Fc)-mediated functions...
December 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28034891/non-neutralizing-antibodies-against-factor-viii-and-risk-of-inhibitor-development-in-patients-with-severe-hemophilia-a
#13
Antonino Cannavò, Carla Valsecchi, Isabella Garagiola, Roberta Palla, Pier Mannuccio Mannucci, Frits R Rosendaal, Flora Peyvandi
The development of anti-factor VIII (FVIII) neutralizing antibodies (inhibitors) is the major complication in hemophilia A. Non-neutralizing antibodies (NNAs) have not only been detected in hemophilia patients but also in unaffected individuals. The aim of this study was to assess the prevalence of NNAs in a cohort of previously untreated or minimally treated patients with hemophilia A, and to evaluate whether their presence is associated with the development of inhibitors. Plasma samples of 237 patients with severe hemophilia A enrolled in the SIPPET trial were collected before any exposure to FVIII concentrates and analyzed for the presence of anti-FVIII NNAs...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/27984065/isolation-and-characterization-of-a-novel-human-scfv-inhibiting-egfr-viii-expressing-cancers
#14
Leila Rahbarnia, Safar Farajnia, Hossein Babaei, Jafar Majidi, Hassan Dariushnejad, Mohammad Kazem Hosseini
EGFRvIII, a mutant form of epidermal growth factor receptor is highly expressed in glioblastoma, carcinoma of the breast, ovary, and lung but not in normal cells. This tumor specific antigen has emerged as a promising candidate for antibody based therapy of several cancers. The aim of the present study was isolation and characterization of a human single chain antibody against EGFRvIII as a promising target for cancer therapy. For this, a synthetic peptide corresponding to EGFRvIII protein was used for screening the naive human scFv phage library...
October 29, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27913544/treatment-of-rare-factor-deficiencies-in-2016
#15
Flora Peyvandi, Marzia Menegatti
Rare bleeding disorders (RBDs) are a heterogeneous group of coagulation disorders characterized by fibrinogen, prothrombin, factors V, VII, X, XI, or XIII (FV, FVII, FX, FXI, or FXIII, respectively), and the combined factor V + VIII and vitamin K-dependent proteins deficiencies, representing roughly 5% of all bleeding disorders. They are usually transmitted as autosomal, recessive disorders, and the prevalence of the severe forms could range from 1 case in 500 000 for FVII up to 1 in 2-3 million for FXIII in the general population...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27904904/clinical-evaluation-of-glycopegylated-recombinant-fviii-efficacy-and-safety-in-severe-haemophilia-a
#16
Paul Giangrande, Tatiana Andreeva, Pratima Chowdary, Silke Ehrenforth, Hideji Hanabusa, Frank W G Leebeek, Steven R Lentz, Laszlo Nemes, Lone Hvitfeldt Poulsen, Elena Santagostino, Chur Woo You, Wan Hui Ong Clausen, Peter G Jönsson, Johannes Oldenburg
Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27891721/extended-half-life-pegylated-full-length-recombinant-factor-viii-for-prophylaxis-in-children-with-severe-haemophilia-a
#17
E S Mullins, O Stasyshyn, M T Alvarez-Román, D Osman, R Liesner, W Engl, M Sharkhawy, B E Abbuehl
INTRODUCTION: Primary factor VIII (FVIII) prophylaxis is the optimal treatment in children with severe haemophilia A. They are expected to benefit from extended half-life (T1/2 ) FVIII coverage by reduced infusion frequency while maintaining haemostatic efficacy. AIMS: To determine immunogenicity, pharmacokinetics (PK), efficacy, safety and quality of life of prophylaxis with a polyethylene glycol (peg)-ylated FVIII (BAX 855) based on full-length recombinant FVIII (ADVATE) in paediatric previously treated patients (PTPs) with severe haemophilia A...
November 27, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/27885373/a-new-era-of-treatment-for-patients-with-haemophilia-a
#18
Robert Klamroth
Treatment and prevention of bleeding episodes in patients with severe haemophilia A require frequent intravenous injection of factor VIII. Inhibitory antibodies against factor VIII occur in approximately 30 % of these patients during the first exposure days and immune tolerance induction to eradicate the inhibitor is challenging. Prevention of bleeds in patients with haemophilia A and inhibitors is less effective and there is ongoing research for alternative treatment options. A promising approach in 2016 is the development of emicizumab (ACE910), a bi-specific IgG antibody to factor IXa and factor X, that mimics the cofactor function of factor VIII...
November 25, 2016: Hämostaseologie
https://www.readbyqxmd.com/read/27868337/enhanced-uptake-of-blood-coagulation-factor-viii-containing-immune-complexes-by-antigen-presenting-cells
#19
R B Hartholt, A Wroblewska, E Herczenik, I Peyron, A Ten Brinke, T Rispens, M A Nolte, E Slot, J W Claassens, F Nimmerjahn, J S Verbeek, J Voorberg
Essentials Anti-factor (F) VIII antibody formation is a major complication in the treatment of hemophilia A. We investigated uptake of FVIII and FVIII immune complex by bone marrow derived dendritic cells. Immune complex formation increased uptake of FVIII 3-4 fold in a Fcγ receptor dependent manner. FVIII immune complex binding to Fcγ receptors may modulate immune tolerance induction. SUMMARY: Background A major complication in the treatment of hemophilia A is the development of inhibitory antibodies targeting coagulation factor VIII (FVIII)...
November 21, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27862687/anti-factor-viii-antibodies-in-brothers-with-haemophilia-a-share-similar-characteristics
#20
J Kahle, A Orlowski, D Stichel, J F Healey, E T Parker, S M Donfield, J Astermark, E Berntorp, P Lollar, D Schwabe, C Königs
INTRODUCTION: The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) is currently the most serious complication for patients with haemophilia A undergoing FVIII replacement therapy. Several genetic factors have been acknowledged as risk factors for inhibitor development. AIM: To analyze the influence of genetic factors on the nature of the humoral immune response to FVIII in eight brother pairs with inhibitors. METHODS: The domain specificity of FVIII-specific IgG was analysed by antibody binding to FVIII fragments and homologue-scanning mutagenesis (HSM)...
November 8, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
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