Anti-factor VIII antibodies of hemophiliac patients are frequently directed towards nonfunctional determinants and do not exhibit isotypic restriction.

Abstract:

:A significant proportion of hemophilia A patients receiving transfusions of factor VIII (FVIII) develop a specific antibody response towards FVIII. These antibodies are usually detected by assays in which they inhibit the function of the molecule, such as the Bethesda clotting test. We have prepared anti-FVIII antibodies by specific immunoadsorption from the plasma of four hemophiliacs with stable inhibitor levels. The isotypic distribution of such antibodies was determined and their capacity to bind to insolubilized FVIII was compared with their inhibitory activity in two functional assays, namely, the Bethesda assay and a chromogenic assay. In addition, the FVIII epitope specificity was determined by competition with monoclonal antibodies for the binding to insolubilized FVIII. We show here that (1) anti-FVIII antibodies are not isotypically restricted; thus, a significant proportion of specific IgG2 was found; (2) antibodies are frequently directed towards epitopes of FVIII that are not directly involved in the function of the molecule and therefore escape detection in the Bethesda method or chromogenic assay; and (3) each patient shows a unique pattern of FVIII epitope recognition. We conclude that evaluation of anti-FVIII antibodies by a functional method does not provide an accurate evaluation of the specific antibody response. These findings have important implications for the comparison of the immunogenicity of FVIII molecules produced by different technologies and for the development of methods to control anti-FVIII antibody production.

journal_name

Blood

journal_title

Blood

authors

Gilles JG,Arnout J,Vermylen J,Saint-Remy JM

subject

Has Abstract

pub_date

1993-10-15 00:00:00

pages

2452-61

issue

8

eissn

0006-4971

issn

1528-0020

journal_volume

82

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Thrombocytopoiesis in normal and sublethally irradiated dogs: response to human interleukin-6.

    abstract::The response of megakaryocytes and platelets to the administration of recombinant human interleukin-6 (IL-6) was investigated in normal and sublethally irradiated dogs. IL-6 was administered for 2 weeks at doses of 10 to 160 micrograms/kg/d to normal animals to assess dose-response and toxicity. Subsequently, 40, 80, ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Burstein SA,Downs T,Friese P,Lynam S,Anderson S,Henthorn J,Epstein RB,Savage K

    更新日期:1992-07-15 00:00:00

  • The carboxyterminal EF domain of erythroid alpha-spectrin is necessary for optimal spectrin-actin binding.

    abstract::Spectrin and protein 4.1R crosslink F-actin, forming the membrane skeleton. Actin and 4.1R bind to one end of β-spectrin. The adjacent end of α-spectrin, called the EF domain, is calmodulin-like, with calcium-dependent and calcium-independent EF hands. The severely anemic sph(1J)/sph(1J) mouse has very fragile red cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-12-260612

    authors: Korsgren C,Lux SE

    更新日期:2010-10-07 00:00:00

  • Applications of high-throughput DNA sequencing to benign hematology.

    abstract::The development of novel technologies for high-throughput DNA sequencing is having a major impact on our ability to measure and define normal and pathologic variation in humans. This review discusses advances in DNA sequencing that have been applied to benign hematologic disorders, including those affecting the red bl...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2013-07-460337

    authors: Sankaran VG,Gallagher PG

    更新日期:2013-11-21 00:00:00

  • Gadd45a regulates hematopoietic stem cell stress responses in mice.

    abstract::Gadd45a has been involved in DNA damage response and in many malignancies, including leukemia. However, the function of Gadd45a in hematopoietic stem cells (HSCs) remains unknown. Here, we reported that Gadd45a-deficient (Gadd45a(-/-)) mice showed a normal hematologic phenotype under homeostatic conditions. However, f...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-05-504084

    authors: Chen Y,Ma X,Zhang M,Wang X,Wang C,Wang H,Guo P,Yuan W,Rudolph KL,Zhan Q,Ju Z

    更新日期:2014-02-06 00:00:00

  • How I treat acute myeloid leukemia in the era of new drugs.

    abstract::The acute myeloid leukemia (AML) treatment landscape has changed substantially since 2017. New targeted drugs have emerged, including venetoclax to target B-cell lymphoma 2, midostaurin and gilteritinib to target FLT3, and ivosidenib and enasidenib to target mutant isocitrate dehydrogenase 1 and 2, respectively. Other...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2019001239

    authors: DiNardo CD,Wei AH

    更新日期:2020-01-09 00:00:00

  • B-cell depletion reactivates B lymphopoiesis in the BM and rejuvenates the B lineage in aging.

    abstract::Aging is associated with a decline in B-lymphopoiesis in the bone marrow and accumulation of long-lived B cells in the periphery. These changes decrease the body's ability to mount protective antibody responses. We show here that age-related changes in the B lineage are mediated by the accumulating long-lived B cells....

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-09-307983

    authors: Keren Z,Naor S,Nussbaum S,Golan K,Itkin T,Sasaki Y,Schmidt-Supprian M,Lapidot T,Melamed D

    更新日期:2011-03-17 00:00:00

  • Relationship between tissue factor expression and deposition of fibrin, platelets, and leukocytes on cultured endothelial cells under venous blood flow conditions.

    abstract::Endothelial cell-mediated coagulation and leukocyte adhesion are processes that might be connected by the generation of thrombin. To examine the interaction of procoagulant and proadhesive activity, cultures of endothelial cells were stimulated with tumor necrosis factor-alpha, which resulted in the surface expression...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kirchhofer D,Sakariassen KS,Clozel M,Tschopp TB,Hadváry P,Nemerson Y,Baumgartner HR

    更新日期:1993-04-15 00:00:00

  • Enhancement of neutrophil function by granulocyte-macrophage colony-stimulating factor involves recruitment of a less responsive subpopulation.

    abstract::Human granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances numerous functions of mature neutrophils (PMN) including phagocytosis, superoxide responses to chemotaxins, antibody-dependent cellular cytotoxicity, and expression of complement receptors. A central question concerns whether the mechanism of enh...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Fletcher MP,Gasson JC

    更新日期:1988-03-01 00:00:00

  • Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia.

    abstract::The risk of development of CNS leukemia was investigated in 153 adults with acute lymphocytic leukemia (ALL) who received systemic combination chemotherapy without CNS prophylaxis. Overall, 31 patients (20%) developed CNS leukemia after a median of 6 months of therapy; the estimated 1-year incidence of CNS leukemia wa...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kantarjian HM,Walters RS,Smith TL,Keating MJ,Barlogie B,McCredie KB,Freireich EJ

    更新日期:1988-11-01 00:00:00

  • Sialyl Lewis(x) (sLe(x)) and an sLe(x) mimetic, CGP69669A, disrupt E-selectin-dependent leukocyte rolling in vivo.

    abstract::Leukocyte rolling is the earliest observable even in their recruitment from the circulation to inflamed tissue. This rolling is mediated largely by interaction between the selectin family of adhesion molecules and their glycosylated ligands. Although the nature of these ligands and their interaction with the selectins...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Norman KE,Anderson GP,Kolb HC,Ley K,Ernst B

    更新日期:1998-01-15 00:00:00

  • Novel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis.

    abstract::Mutations in PIEZO1 are the primary cause of hereditary xerocytosis, a clinically heterogeneous, dominantly inherited disorder of erythrocyte dehydration. We used next-generation sequencing-based techniques to identify PIEZO1 mutations in individuals from 9 kindreds referred with suspected hereditary xerocytosis (HX) ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2017-05-786004

    authors: Glogowska E,Schneider ER,Maksimova Y,Schulz VP,Lezon-Geyda K,Wu J,Radhakrishnan K,Keel SB,Mahoney D,Freidmann AM,Altura RA,Gracheva EO,Bagriantsev SN,Kalfa TA,Gallagher PG

    更新日期:2017-10-19 00:00:00

  • Epstein-Barr virus latent membrane protein-1 oncogene deletions: correlations with malignancy in Epstein-Barr virus--associated lymphoproliferative disorders and malignant lymphomas.

    abstract::LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kingma DW,Weiss WB,Jaffe ES,Kumar S,Frekko K,Raffeld M

    更新日期:1996-07-01 00:00:00

  • Thrombopoietin therapy increases platelet yields in healthy platelet donors.

    abstract::The recombinant thrombopoietins have been shown to be effective stimulators of platelet production in cancer patients. It was therefore of interest to determine if one of these, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), could be used to increase platelet counts and conseque...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood.v98.5.1339

    authors: Kuter DJ,Goodnough LT,Romo J,DiPersio J,Peterson R,Tomita D,Sheridan W,McCullough J

    更新日期:2001-09-01 00:00:00

  • Induction of unscheduled DNA synthesis in human bone marrow cells by bifunctional alkylating agents.

    abstract::A technique has been developed for handling human bone marrow cells intended for the examination of DNA repair synthesis. DNA-repair synthesis, induced by melphalan and nitrogen mustard, was measured as the incorporation of 3H-thymidine, registered by autoradiography as unscheduled DNA synthesis (UDS). Comparison of v...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lewensohn R,Ringborg U

    更新日期:1979-12-01 00:00:00

  • Hemopoietic lineage commitment decisions: in vivo evidence from a transgenic mouse model harboring micro LCR-betapro-LacZ as a transgene.

    abstract::A substantial body of published data suggests activation of lineage-specific genes in multipotential hemopoietic cells before their unilineage commitment. Because the behavior and plasticity of cells isolated in vitro away from microenvironmental constraints exercised in vivo may be altered, one wonders whether simila...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Papayannopoulou T,Priestley GV,Rohde A,Peterson KR,Nakamoto B

    更新日期:2000-02-15 00:00:00

  • Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo.

    abstract::Sickle red cell (SS RBC) adhesion is believed to contribute to the process of vaso-occlusion in sickle cell disease (SCD). We previously found that the LW RBC adhesion receptor can be activated by epinephrine to mediate SS RBC adhesion to endothelial alphavbeta3 integrin. To determine the contribution of LW activation...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-11-056101

    authors: Zennadi R,Moeller BJ,Whalen EJ,Batchvarova M,Xu K,Shan S,Delahunty M,Dewhirst MW,Telen MJ

    更新日期:2007-10-01 00:00:00

  • Irgm1 protects hematopoietic stem cells by negative regulation of IFN signaling.

    abstract::The IFN-inducible immunity-related p47 GTPase Irgm1 has been linked to Crohn disease as well as susceptibility to tuberculosis. Previously we demonstrated that HSC quiescence and function are aberrant in mice lacking Irgm1. To investigate the molecular basis for these defects, we conducted microarray expression profil...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-01-328682

    authors: King KY,Baldridge MT,Weksberg DC,Chambers SM,Lukov GL,Wu S,Boles NC,Jung SY,Qin J,Liu D,Songyang Z,Eissa NT,Taylor GA,Goodell MA

    更新日期:2011-08-11 00:00:00

  • G-CSF-treated granulocytes inhibit acute graft-versus-host disease.

    abstract::It has been shown that in vivo and in vitro treatment with G-CSF induces the generation of low-density granulocytes (LDGs), which copurify with PBMCs and inhibit IFN-gamma production by human T cells. These results prompted us to postulate an immunomodulatory role for LDGs in acute graft-versus-host disease (aGVHD). H...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-08-3239

    authors: Vasconcelos ZF,Dos Santos BM,Farache J,Palmeira TS,Areal RB,Cunha JM,Barcinski MA,Bonomo A

    更新日期:2006-03-01 00:00:00

  • Aging and obesity augment the stress-induced expression of tissue factor gene in the mouse.

    abstract::Hypercoagulability and thrombotic tendency are frequently induced by a variety of stressors. Clinically, aged subjects and obese patients are more susceptible to thrombotic diseases associated with stress, but the underlying mechanisms are unknown. We investigated the expression of a procoagulant gene, tissue factor (...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-03-0945

    authors: Yamamoto K,Shimokawa T,Yi H,Isobe K,Kojima T,Loskutoff DJ,Saito H

    更新日期:2002-12-01 00:00:00

  • How I treat monoclonal gammopathy of renal significance (MGRS).

    abstract::Recently, the term monoclonal gammopathy of renal significance (MGRS) was introduced to distinguish monoclonal gammopathies that result in the development of kidney disease from those that are benign. By definition, patients with MGRS have B-cell clones that do not meet the definition of multiple myeloma or lymphoma. ...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2013-05-495929

    authors: Fermand JP,Bridoux F,Kyle RA,Kastritis E,Weiss BM,Cook MA,Drayson MT,Dispenzieri A,Leung N,International Kidney and Monoclonal Gammopathy Research Group.

    更新日期:2013-11-21 00:00:00

  • Donor statin treatment protects against severe acute graft-versus-host disease after related allogeneic hematopoietic cell transplantation.

    abstract::We retrospectively analyzed outcomes among 567 patients with hematologic malignancies who had hematopoietic cell transplantation from human leukocyte antigen-identical sibling donors between 2001 and 2007 for a correlation between statin use and risk of graft-versus-host disease (GVHD). Compared with allografts where ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-08-240358

    authors: Rotta M,Storer BE,Storb RF,Martin PJ,Heimfeld S,Peffer A,Maloney DG,Deeg HJ,Sandmaier BM,Appelbaum FR,Mielcarek M

    更新日期:2010-02-11 00:00:00

  • Phosphorylation of protein 4.1 in Plasmodium falciparum-infected human red blood cells.

    abstract::The composition of the erythrocyte plasma membrane is extensively modified during the intracellular growth of the malaria parasite Plasmodium falciparum. It has been previously shown that an 80-kD phosphoprotein is associated with the plasma membrane of human red blood cells (RBCs) infected with trophozoite/schizont s...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chishti AH,Maalouf GJ,Marfatia S,Palek J,Wang W,Fisher D,Liu SC

    更新日期:1994-06-01 00:00:00

  • Endothelial cells undergoing apoptosis become proadhesive for nonactivated platelets.

    abstract::Under normal conditions, platelets do not adhere to endothelium. However, when platelets or endothelial cells are stimulated by thrombin or cytokines, respectively, platelets bind avidly to endothelium. Because there is accumulating evidence that endothelial cells may become apoptotic under certain proinflammatory or ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Bombeli T,Schwartz BR,Harlan JM

    更新日期:1999-06-01 00:00:00

  • High-dose therapy and autologous blood stem cell transplantation in POEMS syndrome.

    abstract::We treated 5 patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome and multifocal bone lesions or diffuse bone marrow plasmacytic infiltration with high-dose therapy (HDT) and autologous blood stem cell transplantation. In all cases, the treatment produced...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood.v99.8.3057

    authors: Jaccard A,Royer B,Bordessoule D,Brouet JC,Fermand JP

    更新日期:2002-04-15 00:00:00

  • Primary cutaneous follicle center lymphoma and primary cutaneous large B-cell lymphoma, leg type, are both targeted by aberrant somatic hypermutation but demonstrate differential expression of AID.

    abstract::We assessed primary cutaneous large B-cell lymphoma, leg type (PCLBCL, leg type; n = 13), and primary cutaneous follicle center lymphoma (PCFCL; n = 19) for somatic hypermutation (SHM) of BCL6, and aberrant SHM of MYC, RhoH/TTF, and PAX5. We demonstrate SHM of BCL6 in 8 PCLBCLs (62%), leg type, and 7 PCFCL patients (3...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-08-3443

    authors: Dijkman R,Tensen CP,Buettner M,Niedobitek G,Willemze R,Vermeer MH

    更新日期:2006-06-15 00:00:00

  • Gene expression profiling in CD34 cells to identify differences between aplastic anemia patients and healthy volunteers.

    abstract::An immune pathophysiology for acquired aplastic anemia (AA) has been inferred from the responsiveness of the patients to immunosuppressive therapies and experimental laboratory data. To address the transcriptome of hematopoietic cells in AA, we undertook GeneChip analysis of the extremely limited numbers of progenitor...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-02-0490

    authors: Zeng W,Chen G,Kajigaya S,Nunez O,Charrow A,Billings EM,Young NS

    更新日期:2004-01-01 00:00:00

  • Genome-wide analysis of pediatric-type follicular lymphoma reveals low genetic complexity and recurrent alterations of TNFRSF14 gene.

    abstract::Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-03-703819

    authors: Schmidt J,Gong S,Marafioti T,Mankel B,Gonzalez-Farre B,Balagué O,Mozos A,Cabeçadas J,van der Walt J,Hoehn D,Rosenwald A,Ott G,Dojcinov S,Egan C,Nadeu F,Ramis-Zaldívar JE,Clot G,Bárcena C,Pérez-Alonso V,Endris V,Pe

    更新日期:2016-08-25 00:00:00

  • Expression of plasma glutathione peroxidase in human liver in addition to kidney, heart, lung, and breast in humans and rodents.

    abstract::We analyzed the expression of plasma glutathione peroxidase (GSHPx-P) messenger RNA (mRNA) in mouse, rat, and human tissues, using a human GSHPx-P cDNA clone as the probe. Unlike the classical cellular glutathione peroxidase (GSHPx-1), GSHPx-P expression appears to be tissue-specific. In the mouse and rat, kidney expr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chu FF,Esworthy RS,Doroshow JH,Doan K,Liu XF

    更新日期:1992-06-15 00:00:00

  • Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients.

    abstract::Whereas the chimeric type I anti-CD20 Ab rituximab has improved outcomes for patients with B-cell malignancies significantly, many patients with non-Hodgkin lymphoma (NHL) remain incurable. Obinutuzumab (GA101) is a glycoengineered, humanized anti-CD20 type II Ab that has demonstrated superior activity against type I ...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:10.1182/blood-2012-01-404368

    authors: Salles G,Morschhauser F,Lamy T,Milpied N,Thieblemont C,Tilly H,Bieska G,Asikanius E,Carlile D,Birkett J,Pisa P,Cartron G

    更新日期:2012-05-31 00:00:00

  • Thirty years of hemophilia treatment in the Netherlands, 1972-2001.

    abstract::Since the introduction of replacement therapy in the early 1960s by the infusion of plasma-derived factor VIII and IX preparations, important changes have occurred for hemophilia patients. We studied the medical and social developments over 30 years of hemophilia treatment. Since 1972, 5 cross-sectional national posta...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-05-2008

    authors: Plug I,van der Bom JG,Peters M,Mauser-Bunschoten EP,de Goede-Bolder A,Heijnen L,Smit C,Zwart-van Rijkom JE,Willemse J,Rosendaal FR

    更新日期:2004-12-01 00:00:00