Abstract:
:The present study focuses on a large family with an X-linked immunodeficiency in which there are variable clinical and laboratory phenotypes, including recurrent viral and bacterial infections, hypogammaglobulinemia, Epstein-Barr virus-driven lymphoproliferation, splenomegaly, colitis, and liver disease. Molecular and genetic analyses revealed that affected males were carriers of a hypomorphic hemizygous mutation in XIAP (XIAP(G466X)) that cosegregated with a rare polymorphism in CD40LG (CD40 ligand(G219R)). These genes are involved in the X-linked lymphoproliferative syndrome 2 and the X-linked hyper-IgM syndrome, respectively. Single expression of XIAP(G466X) or CD40L(G219R) had no or minimal effect in vivo, although in vitro, they lead to altered functional activities of their gene products, which suggests that the combination of XIAP and CD40LG mutations contributed to the expression of clinical manifestations observed in affected individuals. Our report of a primary X-linked immunodeficiency of oligogenic origin emphasizes that primary immunodeficiencies are not caused by a single defective gene, which leads to restricted manifestations, but are likely to be the result of an interplay between several genetic determinants, which leads to more variable clinical phenotypes.
journal_name
Bloodjournal_title
Bloodauthors
Rigaud S,Lopez-Granados E,Sibéril S,Gloire G,Lambert N,Lenoir C,Synaeve C,Stacey M,Fugger L,Stephan JL,Fischer A,Picard C,Durandy A,Chapel H,Latour Sdoi
10.1182/blood-2011-01-328849subject
Has Abstractpub_date
2011-07-14 00:00:00pages
252-61issue
2eissn
0006-4971issn
1528-0020pii
blood-2011-01-328849journal_volume
118pub_type
杂志文章相关文献
BLOOD文献大全abstract::Human subjects maintain long-term immunologic memory against infective organisms but the mechanism is unclear. CD4+ T-helper memory (Thmem) cells are pivotal in controlling humoral and cellular responses, therefore their longevity and response to vaccination are critical for maintenance of protective immunity. To prob...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-08-3255
更新日期:2006-04-01 00:00:00
abstract::Interleukin-3 (IL-3) has been shown to be a promising agent in the stimulation of bone marrow regeneration following myeloablative therapy. The biologic half-life of this agent is very short (5 to 15 minutes), which limits the effectiveness of low-dose therapy. Here we show that the biologic effects of low-dose IL-3 i...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-08-15 00:00:00
abstract::Although numerous studies have shown a higher risk of acquiring HIV infection in the presence of other sexually transmitted diseases, the biologic mechanisms responsible for enhanced HIV acquisition are unclear. Because Langerhans cells (LCs) are suspected to be the initial HIV targets after sexual exposure, we studie...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-10-185728
更新日期:2009-05-21 00:00:00
abstract::There have been several new developments in the field of autoimmune neutropenia over the past decade. Neutropenia caused by antibodies directed against granulocyte precursor cells, the oligoclonal nature of antineutrophil antibodies, and the expanding knowledge of neutrophil antigens, particularly in relationship to a...
journal_title:Blood
pub_type: 杂志文章,评审
doi:
更新日期:1993-04-15 00:00:00
abstract::We have previously observed an increased frequency of liver failure in human immunodeficiency virus (HIV)-infected hemophiliacs. The purpose of this study was to quantitate hepatitis C virus (HCV) RNA levels in serial samples from HIV-seropositive (HIV+) and HIV-seronegative (HIV-) hemophiliacs before and after HIV se...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:
更新日期:1994-08-15 00:00:00
abstract::Severe congenital neutropenia (CN) is a preleukemic bone marrow failure syndrome with a 20% risk of evolving into leukemia or myelodysplastic syndrome (MDS). Patterns of acquisition of leukemia-associated mutations were investigated using next-generation deep-sequencing in 31 CN patients who developed leukemia or MDS....
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-11-538025
更新日期:2014-04-03 00:00:00
abstract::We used synthetic peptides to the extracellular loops (ECLs) of CCR5 to examine inhibitory effects on HIV infection/fusion with primary leukocytes and cells expressing recombinant CCR5. We show for the first time that peptides derived from the first, second, or third ECL caused dose-dependent inhibition of fusion and ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-08-2669
更新日期:2004-02-15 00:00:00
abstract::We used both radiolabeled and fluorescein-labeled antiglobulins in assays to detect antibodies against platelets in multiply transfused patients to determine the value of these tests in predicting the outcome of platelet transfusion in such patients. In 15 allosensitized patients, we studied 68 single-donor platelet t...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::Plasmacytoid dendritic cells (PDCs) are crucial effectors in innate immunity. In this study, we show that imatinib, a potent inhibitor of BCR/ABL tyrosine kinase activity, in the presence of Flt3-Ligand, could induce CD34+ progenitors from chronic myeloid leukemia (CML) to give rise in vitro to typical BDCA-2+ type I ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-09-3220
更新日期:2004-06-15 00:00:00
abstract::Genetic variation in the PEAR1 locus is linked to platelet reactivity and cardiovascular disease. The major G allele of rs12041331, an intronic cytosine guanine dinucleotide-single-nucleotide polymorphism (CpG-SNP), is associated with higher PEAR1 expression in platelets and endothelial cells than the minor A allele. ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-11-682153
更新日期:2016-08-18 00:00:00
abstract::The common γ chain (CD132) is a subunit of the interleukin (IL) receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Because levels of several of these cytokines were shown to be increased in the serum of patients developing acute and chronic graft-versus-host disease (GVHD), we reasoned that inhibition of CD132 co...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-06-581793
更新日期:2015-01-15 00:00:00
abstract::The endosteal niche is critical for the maintenance of hematopoietic stem cells (HSCs). However, it consists of a heterogeneous population in terms of differentiation stage and function. In this study, we characterized endosteal cell populations and examined their ability to maintain HSCs. Bone marrow endosteal cells ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-08-239194
更新日期:2010-09-02 00:00:00
abstract::We have retrospectively assessed the neurological manifestations in 34 patients with hemophagocytic lymphohistiocytosis (HLH) in a single center. Clinical, radiological, and cerebrospinal fluid (CSF) cytology data were analyzed according to treatment modalities. Twenty-five patients (73%) had evidence of central nervo...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::Plasmacytoid dendritic cells (pDCs) are specialized DCs that produce high levels of type I IFN upon viral infection. Despite their key immunoregulatory role, little is known about pDC ontogeny or how developmental events regulate their function. We show that mice expressing low levels of the transcription factor Ikaro...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-03-007757
更新日期:2006-12-15 00:00:00
abstract::The outcome of patients with acute myeloid leukemia who are older than 60 years has remained poor because of unfavorable disease characteristics and patient-related factors. The randomized German-Austrian AML Study Group 06-04 protocol was designed on the basis of in vitro synergistic effects of valproic acid (VPA) an...
journal_title:Blood
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1182/blood-2013-12-546283
更新日期:2014-06-26 00:00:00
abstract::The cell-surface receptor c-kit and its cognate ligand stem-cell factor (SCF) or steel factor (SLF) are important for the maintenance of hematopoiesis both in vitro and in vivo. Transforming growth factor-beta (TGF-beta) has been shown to be a potent inhibitor of SLF-mediated synergistic growth of murine Lin-Sca-1+ pr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma characterized by short survival with current therapies, emphasizing the urgent need to develop new therapeutic approaches. Brentuximab vedotin (SGN-35) is an anti-CD30 monoclonal antibody (cAC10) conjugated by a protease-cleavable linker ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-01-481713
更新日期:2013-08-15 00:00:00
abstract::Asparaginase is an enzyme used in the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma in children. It has minimal bone marrow toxicity. Its major side effects are anaphylaxis, pancreatitis, diabetes, coagulation abnormalities, and thrombosis, especially intracranial. It is derived from 2 different...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1182/blood.v99.8.2734
更新日期:2002-04-15 00:00:00
abstract::Chronic myeloid leukemia (CML) is caused by the acquisition of the tyrosine kinase BCR-ABL1 in a hemopoietic stem cell, transforming it into a leukemic stem cell (LSC) that self-renews, proliferates, and differentiates to give rise to a myeloproliferative disease. Although tyrosine kinase inhibitors (TKIs) that target...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2016-09-696013
更新日期:2017-03-23 00:00:00
abstract::The more distal enhancers of the immunoglobulin heavy-chain 3' regulatory region, hs3b and hs4, were recently demonstrated as master control elements of germline transcription and class switch recombination to most immunoglobulin constant genes. In addition, they were shown to enhance the accumulation of somatic mutat...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-12-3827
更新日期:2003-08-15 00:00:00
abstract::A recent clinical trial for adrenoleukodystrophy (ALD) showed the efficacy and safety of lentiviral vector (LV) gene transfer in hematopoietic stem progenitor cells. However, several common insertion sites (CIS) were found in patients' cells, suggesting that LV integrations conferred a selective advantage. We performe...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-09-306761
更新日期:2011-05-19 00:00:00
abstract::In ischemic stroke, treatment options are limited. Therapeutic thrombolysis is restricted to the first few hours after stroke, and the utility of current platelet aggregation inhibitors, including GPIIb/IIIa receptor antagonists, and anticoagulants is counterbalanced by the risk of intracerebral bleeding complications...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2008-04-144758
更新日期:2008-11-01 00:00:00
abstract::Although proinflammatory cytokines are key mediators of tissue damage during graft-versus-host disease (GVHD), IFNgamma has previously been attributed with both protective and pathogenic effects. We have resolved this paradox by using wild-type (wt), IFNgamma(-/-), and IFNgammaR(-/-) mice as donors or recipients in we...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-12-063982
更新日期:2007-08-01 00:00:00
abstract::There is evidence from clinical studies and animal experiments that aspirin has a greater antithrombotic activity in males compared to females. We investigated platelet function in vitro and in vivo in rabbits before and after the administration of a dose of aspirin (5 mg/kg) which inhibited collagen stimulated thromb...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::Activation of Fas antigen, a cell surface receptor molecule, by its ligand results in transduction of a signal for cell death. The Fas system has been implicated in target cell recognition, clonal development of immune effector cells, and termination of the cellular immune response. Fas antigen expression on lymphocyt...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::The t(1;19)(q23;p13) chromosomal translocation is observed cytogenetically in 25% of children with pre-B-cell acute lymphoblastic leukemia (ALL) and is associated with an adverse treatment outcome. The t(1;19) juxtaposes the E2A gene from chromosome 19 with the PBX1 gene on chromosome 1, leading to the production of f...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-02-15 00:00:00
abstract::Acute chest syndrome (ACS) is a leading cause of death in sickle cell disease (SCD). Our previous work showed that hypoxia enhances the ability of sickle erythrocytes to adhere to human microvessel endothelium via interaction between very late activation antigen-4 (VLA4) expressed on sickle erythrocytes and the endoth...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is characterized by delayed senescence and slow accumulation of monoclonal, small lymphocytes. Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine that plays a role in hematopoiesis and apoptosis. Elevated bFGF levels have been detected in urine from patients with a varie...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::We have developed a new helper-dependent (HD) adenoviral vector FTC that contains 3 cis-acting sequences as stuffer DNA: a human fragment of alphoid repeat DNA, matrix-attachment regions (MARs), and the hepatocyte control region enhancer. To determine the most robust human coagulation factor IX (hFIX) expression casse...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.11.3923
更新日期:2002-06-01 00:00:00
abstract::Mice deficient in c-fms-like tyrosine kinase 3 (FLT3) signaling have reductions in early multipotent and lymphoid progenitors, whereas no evident myeloid phenotype has been reported. However, activating mutations of Flt3 are among the most common genetic events in acute myeloid leukemia and mice harboring internal tan...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-12-258756
更新日期:2010-06-17 00:00:00