Abstract:
:CD27, a tumor necrosis factor receptor family member, interacts with CD70 and influences T-, B- and NK-cell functions. Disturbance of this axis impairs immunity and memory generation against viruses including Epstein Barr virus (EBV), influenza, and others. CD27 is commonly used as marker of memory B cells for the classification of B-cell deficiencies including common variable immune deficiency. Flow cytometric immunophenotyping including expression analysis of CD27 on lymphoid cells was followed by capillary sequencing of CD27 in index patients, their parents, and non-affected siblings. More comprehensive genetic analysis employed single nucleotide polymorphism-based homozygosity mapping and whole exome sequencing. Analysis of exome sequencing data was performed at two centers using slightly different data analysis pipelines, each based on the Genome Analysis ToolKit Best Practice version 3 recommendations. A comprehensive clinical characterization was correlated to genotype. We report the simultaneous confirmation of human CD27 deficiency in 3 independent families (8 patients) due to a homozygous mutation (p. Cys53Tyr) revealed by whole exome sequencing, leading to disruption of an evolutionarily conserved cystein knot motif of the transmembrane receptor. Phenotypes varied from asymptomatic memory B-cell deficiency (n=3) to EBV-associated hemophagocytosis and lymphoproliferative disorder (LPD; n=3) and malignant lymphoma (n=2; +1 after LPD). Following EBV infection, hypogammaglobulinemia developed in at least 3 of the affected individuals, while specific anti-viral and anti-polysaccharide antibodies and EBV-specific T-cell responses were detectable. In severely affected patients, numbers of iNKT cells and NK-cell function were reduced. Two of 8 patients died, 2 others underwent allogeneic hematopoietic stem cell transplantation successfully, and one received anti-CD20 (rituximab) therapy repeatedly. Since homozygosity mapping and exome sequencing did not reveal additional modifying factors, our findings suggest that lack of functional CD27 predisposes towards a combined immunodeficiency associated with potentially fatal EBV-driven hemo-phagocytosis, lymphoproliferation, and lymphoma development.
journal_name
Haematologicajournal_title
Haematologicaauthors
Salzer E,Daschkey S,Choo S,Gombert M,Santos-Valente E,Ginzel S,Schwendinger M,Haas OA,Fritsch G,Pickl WF,Förster-Waldl E,Borkhardt A,Boztug K,Bienemann K,Seidel MGdoi
10.3324/haematol.2012.068791subject
Has Abstractpub_date
2013-03-01 00:00:00pages
473-8issue
3eissn
0390-6078issn
1592-8721pii
haematol.2012.068791journal_volume
98pub_type
杂志文章相关文献
HAEMATOLOGICA文献大全abstract:BACKGROUND:Cutaneous T-cell lymphomas (CTCL) represent about the 80% of skin lymphomas and comprise a heterogeneous group of diseases with respect to clinical presentation, outcome, histologic and immunophenotypic features. In the recent years, data have been accumulated indicating that clinical and biological differen...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:
更新日期:2004-11-01 00:00:00
abstract::Pseudomonas aeruginosa is one leading gram-negative organism associated with nosocomial infections. Bacteremia is life-threatening in the immunocompromised host. Increasing frequency of multi-drug-resistant (MDRPA) strains is concerning. We started a retrospective survey in the pediatric hematology oncology Italian ne...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:10.3324/haematol.2009.020867
更新日期:2010-09-01 00:00:00
abstract::The role of reduced intensity allogeneic stem cell transplantation for the treatment of relapsed/refractory Hodgkin's lymphoma remains controversial. We retrospectively analyzed 191 patients who underwent reduced intensity allogeneic stem cell transplantation between 1998 and 2008 for relapsed or refractory Hodgkin's ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2012.080895
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Patients with acute myeloblastic leukemia (AML) with features of myelodysplastic syndrome and abnormalities of megakaryocytopoiesis often have cytogenetic aberrations of 3q21 and 3q26 bands involving the paracentric inversion [inv(3) (q21q26)] or a reciprocal translocation [t(3;3) (q21;q26)]. ...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2003-11-01 00:00:00
abstract::We quantified Wilm's tumor gene (WT1) using a real time quantitative polymerase chain reaction in 20 adult patients with acute lymphoblastic leukemia at presentation. A WT1 level greater than 906 (median value for the whole series) was a significant predictor of a poor disease-free and overall survival in uni- and mul...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:Pediatric acute myeloid leukemia is a heterogeneous disease characterized by non-random genetic aberrations related to outcome. The genetic subtype is currently detected by different diagnostic procedures which differ in success rate and/or specificity. DESIGN AND METHODS:We examined the potential of gene e...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2010.029660
更新日期:2011-02-01 00:00:00
abstract::We evaluate the long-term results of a prospective clinical study enrolling more than 100 adult patients with Burkitt lymphoma/leukemia. Depending on extent of disease, treatment consisted of six to eight rituximab infusions and four to six courses of intensive chemotherapy (attenuated in patients aged >55 years) with...
journal_title:Haematologica
pub_type: 临床试验,杂志文章,多中心研究
doi:10.3324/haematol.2013.086827
更新日期:2013-11-01 00:00:00
abstract::Post-transfusion hepatitis (PTH) is a major problem in patients with acute leukemias requiring blood products during induction or consolidation therapy. In fact, PTH causes delays of chemotherapy with major violations in the timing of protocols. In order to assess the efficacy and safety of a short course of alpha-int...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::The objective of this study was to create a bioclinical model, based on clinical and molecular predictors of event-free and overall survival for relapsed/refractory diffuse large B-cell lymphoma patients treated on the Canadian Cancer Trials Group (CCTG) LY12 prospective study. In 91 cases, sufficient histologic mater...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:10.3324/haematol.2017.179309
更新日期:2018-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:CD20 has been proposed as a novel suicide gene system for the treatment of graft-versus-host disease (GVHD), a fatal complication of allogeneic bone marrow transplantation: indeed expression of the human non-immunogenic exogenous CD20 protein allows positive immunoselection of transduced cells...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:To assess the efficacy and the toxic profile of gemcitabine, a novel pyrimidine antimetabolite active against several solid tumors, we carried out a study in heavily pretreated Hodgkin's disease (HD) patients. DESIGN AND METHODS:From May 1997 to January 1999, 14 pretreated patients (10 relaps...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract::Granulocyte colony-stimulating factor (G-CSF) can be administered after a peripheral blood stem cell transplantation with the aim of accelerating neutrophil recovery. In a randomized, single-blind study we studied a new administration schedule of G-CSF in this context. ...
journal_title:Haematologica
pub_type: 临床试验,信件,随机对照试验
doi:
更新日期:2004-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:To compare the clinical results of two consecutive therapeutic protocols including autologous blood stem cell transplantation (ABSCT) for patients with de novo acute myeloblastic leukemia (AML) in first complete remission (CR1). DESIGN AND METHODS:Between November 1989 and January 1997, 50 pat...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:
更新日期:1999-02-01 00:00:00
abstract::The dic(9;20)(p11-13;q11) is a recurrent chromosomal abnormality in patients with acute lymphoblastic leukemia. Although it results in loss of material from 9p and 20q, the molecular targets on both chromosomes have not been fully elucidated. From an initial cohort of 58 with acute lymphoblastic leukemia patients with...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2008.002808
更新日期:2009-08-01 00:00:00
abstract::The tumor suppressor phosphatase and tensin homolog (PTEN) negatively regulates phosphatidylinositol 3-kinase (PI3K)-AKT signaling and is often inactivated by mutations (including deletions) in a variety of cancer types, including T-cell acute lymphoblastic leukemia. Here we review mutation-associated mechanisms that ...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:10.3324/haematol.2016.146381
更新日期:2016-09-01 00:00:00
abstract::Since HA-1-specific T cells have been shown to make a significant contribution to the clinical responses in patients with relapsed leukemia, we investigated the feasibility of adoptive transfer of in vitro induced HA-1-specific CD8 positive T cells to patients with relapsed leukemia after allogeneic stem cell transpla...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2011.053371
更新日期:2012-08-01 00:00:00
abstract::In contrast to well-established hierarchical concepts of tumor stem cells, leukemia-initiating cells in B-cell precursor acute lymphoblastic leukemia have not yet been phenotypically identified. Different subpopulations, as defined by surface markers, have shown equal abilities to reconstitute leukemia upon transplant...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2017.167502
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Most minimal residual disease-directed treatment interventions in current treatment protocols for acute lymphoblastic leukemia are based on bone marrow testing, which is a consequence of previous studies showing the superiority of bone marrow over peripheral blood as an investigational material. Those studie...
journal_title:Haematologica
pub_type: 临床试验,杂志文章,多中心研究
doi:10.3324/haematol.2011.042937
更新日期:2011-12-01 00:00:00
abstract::It is currently unknown whether immunosuppressive therapy or hematopoietic stem cell transplantation is the most appropriate treatment strategy for children with refractory cytopenia and normal karyotype or trisomy 8. We report on 31 children with hypoplastic refractory cytopenia treated with immunosuppressive therapy...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.10683
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:Human cytomegalovirus infection is the most frequent viral complication in patients undergoing hematopoietic stem cell transplantation. We investigated the development of human cytomegalovirus-specific T cells in adult recipients of hematopoietic stem cell transplants. DESIGN AND METHODS:From May 2003 throu...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.11912
更新日期:2008-02-01 00:00:00
abstract::The effect of treatment with 1,25-dihydroxyvitamin D3 administered at the dose of 1.50-3.00 ug/day for at least 12 months was evaluated in three patients with idiopathic myelofibrosis and in five patients with idiopathic thrombocythemia. This treatment did not cause any significant change in the hematological values o...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::We describe the case of a 12-year old boy with Hoyeraal-Hreidarsson Syndrome (HHS). This syndrome includes intrauterine growth retardation, microcephaly, mental retardation, cerebellar malformation, and pancytopenia. HHS is a severe multisystem disorder associated with premature mortality, due to bone marrow failure. ...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
abstract::VAD is the most active regimen in refractory myeloma patients; however, the role of vincristine and doxorubicin remains unclear. Relatively high doses of cyclophosphamide (3.6 g/sqm) increased the response rate and survival in resistant MM. Cyclophosphamide and dexamethasone were administered to 28 patients with advan...
journal_title:Haematologica
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1997-05-01 00:00:00
abstract::The detection of iron deficiency anemia is challenged by the paucity of diagnostic tests demonstrating high sensitivity and specificity. Using two biomarkers, zinc-protoporphyrin/heme and hepcidin, we established the diagnostic cut-off values for iron deficiency anemia in preschool children and women. We randomly sele...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2018.193243
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Recently, a chimeric monoclonal antibody (MoAb) directed against the CD20 antigen (rituximab) has been successfully introduced in the treatment of several CD20-positive B-cell neoplasias and particularly of follicular lymphomas. Based on these premises we evaluated the efficacy and the toxicit...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::In order to overcome the problem of different control genes for BCR-ABL normalization, we used a linear regression equation to compare our results previously obtained using B2M as the control gene with those calculated using the ABL gene and validated the slope as a factor to convert from B2M to ABL results. ...
journal_title:Haematologica
pub_type: 信件
doi:10.3324/haematol.10632
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:Phosphatidylserine exposure by red blood cells is acknowledged as a signal that initiates phagocytic removal of the cells from the circulation. Several disorders and conditions are known to induce phosphatidylserine exposure. Removal of phosphatidylserine-exposing red blood cells generally occurs by macropha...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2011.048694
更新日期:2012-04-01 00:00:00
abstract::Home care (HC) has an increasingly expanding role in the global management of patients affected by hematologic malignancies. Integrated strategies, including causal-targeted and supportive treatments according to hematologic expertise and a holistic approach inspired by the philosophy and practice of palliative medici...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:
更新日期:2006-11-01 00:00:00
abstract::Hematopoietic differentiation is driven by transcription factors, which orchestrate a finely tuned transcriptional network. At bipotential branching points lineage decisions are made, where key transcription factors initiate cell type-specific gene expression programs. These programs are stabilized by the epigenetic a...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2017.174516
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Classical Hodgkin's lymphoma is characterized by a minority of neoplastic cells surrounded by a heterogeneous background population of non-neoplastic cells including lymphoma-associated macrophages. High levels of expression of both the monocyte/macrophage lineage-associated antigens CD68 and CD163 have been...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2010.031542
更新日期:2011-02-01 00:00:00