Abstract:
:The clinical hallmark of paroxysmal nocturnal hemoglobinuria (PNH) is chronic intravascular hemolysis that is a consequence of unregulated activation of the alternative pathway of complement (APC). Intravascular hemolysis can be inhibited in patients by treatment with eculizumab, a monoclonal antibody that binds complement C5 thereby preventing formation of the cytolytic membrane attack complex of complement. However, in essentially all patients treated with eculizumab, persistent anemia, reticulocytosis, and biochemical evidence of hemolysis are observed; and in a significant proportion, their PNH erythrocytes become opsonized with complement C3. These observations suggest that PNH patients treated with eculizumab are left with clinically significant immune-mediated hemolytic anemia because the antibody does not block APC activation. With a goal of improving PNH therapy, we characterized the activity of anti-C3b/iC3b monoclonal antibody 3E7 in an in vitro model of APC-mediated hemolysis. We show that 3E7 and its chimeric-deimmunized derivative H17 block both hemolysis and C3 deposition on PNH erythrocytes. The antibody is specific for the APC C3/C5 convertase because classical pathway-mediated hemolysis is unaffected by 3E7/H17. These findings suggest an approach to PNH treatment in which both intravascular and extravascular hemolysis can be inhibited while preserving important immune functions of the classical pathway of complement.
journal_name
Bloodjournal_title
Bloodauthors
Lindorfer MA,Pawluczkowycz AW,Peek EM,Hickman K,Taylor RP,Parker CJdoi
10.1182/blood-2009-09-244285subject
Has Abstractpub_date
2010-03-18 00:00:00pages
2283-91issue
11eissn
0006-4971issn
1528-0020pii
blood-2009-09-244285journal_volume
115pub_type
杂志文章相关文献
BLOOD文献大全abstract::Administration of cyclosporine A (CsA) after autologous stem cell transplantation elicits an autoimmune syndrome with pathology similar to graft-versus-host disease (GVHD). This syndrome, termed autologous GVHD, is associated with the appearance of autoreactive T cells directed at major histocompatibility class (MHC) ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.3.868
更新日期:2001-08-01 00:00:00
abstract::Retrospective studies of patients with thrombotic microangiopathies (TMAs) have shown that a deficient activity of von Willebrand factor (vWF)-cleaving protease is involved in thrombotic thrombocytopenic purpura (TTP) but not in the hemolytic-uremic syndrome (HUS). To further analyze the relevance of this enzymatic ac...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood.v98.6.1765
更新日期:2001-09-15 00:00:00
abstract::Tissue factor-induced blood coagulation was studied in 20 individuals, for varying periods of time during 54 months, in contact pathway-inhibited whole blood at 37 degrees C and evaluated in terms of the activation of various substrates. After quenching over time with inhibitors, the soluble phases were analyzed for t...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v100.1.148
更新日期:2002-07-01 00:00:00
abstract::We evaluated a treatment strategy targeting both lymphoma cells (by rituximab) and the microenvironment (by thalidomide) in 16 patients with relapsed/refractory mantle cell lymphoma (MCL). Rituximab was administered at 375 mg/m(2) for 4 weekly doses concomitantly with thalidomide (200 mg daily, with a dose increment t...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2004-03-1091
更新日期:2004-10-15 00:00:00
abstract::This prospective multicenter study examined whether simultaneous administration of granulocyte colony-stimulating factor (G-CSF; Filgrastim) and induction chemotherapy for adult acute lymphoblastic leukemia (ALL) could prevent treatment-related neutropenia, infections, and resulting treatment delays. Seventy-six patie...
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:
更新日期:1995-07-15 00:00:00
abstract::Heparin-induced thrombocytopenia (HIT) with thrombosis is a serious complication of heparin use. HIT sera can generate platelet-derived microparticles, which are produced in a heparin-dependent manner and are hypothesized to be important initial pathological participants because they promote vascular occlusion. To dat...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract::Localized tumors composed of immature cells of the myelogenous series have been recognized for many years as an uncommon manifestation of granulocytic leukemia. The histologic diagnosis of chloroma (granulocytic sarcoma) may be extremely difficult when the myeloblastic cells are poorly differentiated and the tumor lac...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-07-01 00:00:00
abstract::High-dose chemoradiotherapy (HDT) with autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed aggressive non-Hodgkin lymphoma (NHL). However, its role in the treatment of patients with primary refractory disease is not well defined. The outcomes of 85 patients with primary re...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-10-01 00:00:00
abstract::Karyotypes in multiple myeloma (MM) are complex and exhibit numerous structural and numerical aberrations. The largest subset of structural chromosome anomalies in clinical specimens and cell lines involves aberrations of chromosome 1. Unbalanced translocations and duplications involving all or part of the whole long ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract::Receptors for the Fc portion of IgG (FcγRs) are mandatory for the induction of various IgG-dependent models of autoimmunity, inflammation, anaphylaxis, and cancer immunotherapy. A few FcγRs have the ability to bind monomeric IgG: high-affinity mouse mFcγRI, mFcγRIV, and human hFcγRI. All others bind IgG only when aggr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-07-442541
更新日期:2013-02-28 00:00:00
abstract::The principal aim of our study was to investigate whether patients transplanted more than 20 years ago for β-thalassemia major had a different health-related quality of life (HRQoL) compared with the general population. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Functional Assessment o...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-05-502658
更新日期:2013-09-26 00:00:00
abstract::Increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (aGVHD) in stem cell transplantation (SCT). Fecal microbiota transplantation (FMT) could represent an alternative treatment option for aGVHD. However, FMT for SCT patients carries a potential risk of infect...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2016-05-717652
更新日期:2016-10-20 00:00:00
abstract::CD8+ Foxp3+ T cells (Tregs) are a potent regulatory population whose functional and ontological similarities to CD4+ Fox3+ T cells have not been well delineated. Using an experimental model of graft-versus-host disease (GVHD), we observed that CD8+ Tregs were significantly less potent than CD4+ Tregs for the suppressi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-09-807156
更新日期:2018-07-26 00:00:00
abstract::Acute myeloid leukemia (AML) is one of the most common acute leukemias in adults and children, yet significant numbers of patients relapse and die of disease. In this study, we identify the dependence of AML blasts on arginine for proliferation. We show that AML blasts constitutively express the arginine transporters ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-09-600643
更新日期:2015-04-09 00:00:00
abstract::The Hermes receptor CD44 is a multifunctional adhesion molecule that plays an essential role in the homing and invasion of neoplastic stem cells in various myeloid malignancies. Although mast cells (MCs) reportedly express CD44, little is known about the regulation and function of this receptor in neoplastic cells in ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2018-02-833582
更新日期:2018-11-01 00:00:00
abstract::Evidence has been provided recently that shows that high concentrations of cytokines can fulfill functions previously attributed to stromal cells, such as promote the survival of, and led to a net increase in human primitive progenitors initiating long-term cultures in vitro (LTC-IC) or engrafting NOD-SCID (nonobese d...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-07-15 00:00:00
abstract::The signals that mediate T-cell infiltration during T-cell autoimmune diseases are poorly understood. The chemokine CCL21 (originally isolated by us and others as Exodus-2/6Ckine/SLC/TCA4) is highly potent and highly specific for stimulating T-cell migration. However, it is thought to be expressed only in secondary ly...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-05-1586
更新日期:2003-02-01 00:00:00
abstract::Steroid-resistant or steroid-refractory acute graft-versus-host disease (SR-aGVHD) poses one of the most vexing challenges faced by providers who care for patients after allogeneic hematopoietic cell transplantation. For the past 4 decades, research in the field has been driven by the premise that persistent graft-ver...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019000960
更新日期:2020-05-07 00:00:00
abstract::Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00
abstract::To investigate the heterogeneous cellular structure of human acute myeloid leukemia (AML), subpopulations of cells were distinguished by two combined criteria: proliferation and differentiation. Purified blast cells were fractionated from blood or bone marrow of patients with newly diagnosed AML and colonies and clust...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-03-01 00:00:00
abstract::The combination of cyclophosphamide, vincristine, and prednisone (CVP) is one of several standard treatment options for advanced follicular lymphoma. This, like similar chemotherapeutic regimens, induces response rates of 60% to 80%, with a median response duration of under 2 years. Rituximab, a chimeric monoclonal an...
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-2004-08-3175
更新日期:2005-02-15 00:00:00
abstract::To determine whether the erythropoietin receptor (Epo-R) plays a role in the course of malignant erythropoietic disorders, this gene was studied in murine and human erythroleukemia cells. An altered Epo-R gene was found in a murine Friend erythroleukemia cell line, FCL1, due to a spleen focus-forming virus (SFFV) long...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::Epidemiologic studies have correlated elevated plasma fibrinogen (hyperfibrinogenemia) with risk of cardiovascular disease and arterial and venous thrombosis. However, it is unknown whether hyperfibrinogenemia is merely a biomarker of the proinflammatory disease state or is a causative mechanism in the etiology. We ra...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-11-316885
更新日期:2011-05-05 00:00:00
abstract::In France, more than 80% of children with Burkitt's lymphoma or Burkitt's leukemia (ALL3) are now cured with the LMB (B-cell non-Hodgkin's lymphoma and B-ALL) protocols of the Société Française d'Oncologie Pédiatrique, but so far, poor results have been obtained in the few adult studies available. We have analyzed the...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::Human plasma fibrinogen is produced by liver parenchymal cells. Such molecules contain two classes of gamma-chains (gamma A, gamma'), which differ with respect to their COOH-terminal sequences. When fibrin is crosslinked in the presence of factor XIIIa and Ca2+, three types of gamma-dimer are formed (gamma A-gamma A; ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::We used the polymerase chain reaction (PCR) to detect ALL1-AF4 rearrangements, the molecular hallmark of t(4;11) in a series of 46 pre-pre-B (CD19+, CD24+, CD10/CD20/cylgM/sIgM-) acute lymphoblastic leukemias (ALL). Eighteen patients (39%) exhibited fusion transcripts including 4 of 12 children and 14 of 34 adults. Th...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population that shares certain characteristics including an aberrant myeloid phenotype and the ability to suppress T cells. MDSCs have been predominantly studied in malignant diseases and findings suggest involvement in tumor-associated immune suppress...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2013-12-546416
更新日期:2014-07-31 00:00:00
abstract::Between February 1996 and December 2004, the German Leukemia Study Initiative registered 1766 consecutive patients for the acute myeloid leukemia (AML) 96 study, all of whom were diagnosed by central cytomorphology according to the French-American-British (FAB) and the new World Health Organization (WHO) classificatio...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2007-08-101162
更新日期:2008-02-15 00:00:00
abstract::A noninferiority study was performed comparing low-dose and standard-dose prophylactic platelet transfusions. A double-blind randomized controlled trial (RCT) was performed in 6 sites in 3 countries. Thrombocytopenic adults requiring prophylactic platelet transfusion were randomly allocated to standard-dose (300-600 x...
journal_title:Blood
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1182/blood-2008-09-178236
更新日期:2009-02-12 00:00:00
abstract::Although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for patients with Fanconi anemia (FA), published series mostly refer to single-center experience with limited numbers of patients. We analyzed results in 795 patients with FA who underwent first HSCT between May 1972...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2013-01-479733
更新日期:2013-12-19 00:00:00