The Experts below are selected from a list of 65160 Experts worldwide ranked by ideXlab platform
Morris Kletzel - One of the best experts on this subject based on the ideXlab platform.
-
correction of neutropenia and hypogammaglobulinemia in x linked hyper igm syndrome by allogeneic bone marrow transplantation
Bone Marrow Transplantation, 1998Co-Authors: Paul Scholl, Maurice R G Ogorman, Lauren M Pachman, Paul R Haut, Morris KletzelAbstract:X-linked hyper-IgM (X-HIM) syndrome is a primary Immunodeficiency Disease characterized by defects in both cellular and humoral immunity. X-HIM is caused by mutations in the gene for CD40 ligand (CD40L), a T cell membrane protein that mediates T cell-dependent immune functions. We report the case of a 6-year-old male with X-HIM due to an intronic mutation resulting in aberrant CD40L RNA splicing and absence of detectable CD40L protein. The patient had a history of multiple infectious complications and chronic neutropenia requiring treatment with recombinant granulocyte colony-stimulating factor, and underwent allogeneic bone marrow transplantation from an HLA-matched sibling donor. Following successful engraftment, T cell CD40L expression and immunoglobulin isotype switching were reconstituted and neutropenia resolved. Allogeneic bone marrow transplantation can correct neutropenia and reconstitute immune function in X-HIM.
Jennifer M Puck - One of the best experts on this subject based on the ideXlab platform.
-
history and current status of newborn screening for severe combined Immunodeficiency
Seminars in Perinatology, 2015Co-Authors: Antonia Kwan, Jennifer M PuckAbstract:The development of a T-cell receptor excision circle (TREC) assay utilizing dried blood spots in universal newborn screening has allowed the early detection of T-cell lymphopenia in newborns. Diagnosis of severe combined Immunodeficiency (SCID) in affected infants in the neonatal period, while asymptomatic, permits early treatment and restoration of a functional immune system. SCID was the first Immunodeficiency Disease to be added to the Recommended Uniform Screening Panel of Core Conditions in the United States in 2010, and it is now implemented in 26 states in the U.S. This review covers the development of newborn screening for SCID, the biology of the TREC test, its current implementation in the U.S., new findings for SCID in the newborn screening era, and future directions.
-
establishing diagnostic criteria for severe combined Immunodeficiency Disease scid leaky scid and omenn syndrome the primary immune deficiency treatment consortium experience
The Journal of Allergy and Clinical Immunology, 2014Co-Authors: William T Shearer, Luigi D. Notarangelo, Elizabeth Dunn, Christopher C Dvorak, Jennifer M Puck, Brent R Logan, Linda M Griffith, Donald B Kohn, Richard J Oreilly, Thomas A FleisherAbstract:Background The approach to the diagnosis of severe combined Immunodeficiency Disease (SCID) and related disorders varies among institutions and countries. Objectives The Primary Immune Deficiency Treatment Consortium attempted to develop a uniform set of criteria for diagnosing SCID and related disorders and has evaluated the results as part of a retrospective study of SCID in North America. Methods Clinical records from 2000 through 2009 at 27 centers in North America were collected on 332 children treated with hematopoietic stem cell transplantation (HCT), enzyme replacement therapy, or gene therapy for SCID and related disorders. Eligibility for inclusion in the study and classification into Disease groups were established by using set criteria and applied by an expert review group. Results Two hundred eighty-five (86%) of the patients were determined to be eligible, and 47 (14%) were not eligible. Of the 285 eligible patients, 84% were classified as having typical SCID; 13% were classified as having leaky SCID, Omenn syndrome, or reticular dysgenesis; and 3% had a history of enzyme replacement or gene therapy. Detection of a genotype predicting an SCID phenotype was accepted for eligibility. Reasons for noneligibility were failure to demonstrate either impaired lymphocyte proliferation or maternal T-cell engraftment. Overall (n = 332) rates of testing were as follows: proliferation to PHA, 77%; maternal engraftment, 35%; and genotype, 79% (mutation identified in 62%). Conclusion Lack of complete laboratory evaluation of patients before HCT presents a significant barrier to definitive diagnosis of SCID and related disorders and prevented inclusion of subjects in our observational HCT study. This lesson is critical for patient care, as well as the design of future prospective treatment studies for such children because a well-defined and consistent study population is important for precision in outcomes analysis.
-
laboratory technology for population based screening for severe combined Immunodeficiency in neonates the winner is t cell receptor excision circles
The Journal of Allergy and Clinical Immunology, 2012Co-Authors: Jennifer M PuckAbstract:The most profound primary Immunodeficiency Disease, severe combined Immunodeficiency (SCID), is fatal in infancy unless affected infants are provided with an adaptive immune system through allogeneic hematopoietic cell transplantation, enzyme replacement, or gene therapy. However, most infants with SCID lack a family history or any clinical clues before the onset of infections, making this serious but treatable Disease a candidate for population-based newborn screening. Of several approaches considered for SCID screening, testing for T-cell receptor excision circles (TRECs), a DNA biomarker of normal T-cell development, has proved successful. TREC numbers can be measured in DNA isolated from the dried bloodspots already routinely collected for newborn screening. Infants with low or absent TRECs can thus be identified and referred for confirmatory testing and prompt intervention. TREC testing of newborns is now being performed in several states, indicating that this addition to the newborn screening panel can be successfully integrated into state public health programs.
-
improving cellular therapy for primary immune deficiency Diseases recognition diagnosis and management
The Journal of Allergy and Clinical Immunology, 2009Co-Authors: Linda M Griffith, Luigi D. Notarangelo, Jennifer M Puck, Thomas A Fleisher, Morton J Cowan, Rebecca H Buckley, Fabio Candotti, Mary Ellen Conley, Bobby H Gaspar, Donald B KohnAbstract:More than 20 North American academic centers account for the majority of hematopoietic stem cell transplantation (HCT) procedures for primary Immunodeficiency Diseases (PIDs), with smaller numbers performed at additional sites. Given the importance of a timely diagnosis of these rare Diseases and the diversity of practice sites, there is a need for guidance as to best practices in management of patients with PIDs before, during, and in follow-up for definitive treatment. In this conference report of immune deficiency experts and HCT physicians who care for patients with PIDs, we present expert guidance for (1) PID diagnoses that are indications for HCT, including severe combined Immunodeficiency Disease (SCID), combined Immunodeficiency Disease, and other non-SCID Diseases; (2) the critical importance of a high degree of suspicion of the primary care physician and timeliness of diagnosis for PIDs; (3) the need for rapid referral to an immune deficiency expert, center with experience in HCT, or both for patients with PIDs; (4) medical management of a child with suspicion of SCID/combined Immunodeficiency Disease while confirming the diagnosis, including infectious Disease management and workup; (5) the posttransplantation follow-up visit schedule; (6) antimicrobial prophylaxis after transplantation, including gamma globulin administration; and (7) important indications for return to the transplantation center after discharge. Finally, we discuss the role of high-quality databases in treatment of PIDs and HCT as an element of the infrastructure that will be needed for productive multicenter clinical trials in these rare Diseases.
Siobhan O Burns - One of the best experts on this subject based on the ideXlab platform.
-
how i manage patients with wiskott aldrich syndrome
British Journal of Haematology, 2019Co-Authors: Elizabeth Rivers, Adrian J. Thrasher, Austen Worth, Siobhan O BurnsAbstract:Wiskott Aldrich syndrome (WAS) is a primary Immunodeficiency Disease resulting in recurrent infections, eczema and microthrombocytopaenia. In its classical form, significant combined immune deficiency, autoimmune complications and risk of haematological malignancy necessitate early correction with stem cell transplantation or gene therapy. A milder form, X-linked thrombocytopaenia (XLT), shares similar bleeding risk from thrombocytopaenia but is not associated with other significant clinical features and is generally managed conservatively. Here, we detail our approach to the diagnosis and treatment of classical WAS and XLT.
Haiyan Zhang - One of the best experts on this subject based on the ideXlab platform.
-
comprehensive review of autoantibodies in patients with hyper igm syndrome
Cellular & Molecular Immunology, 2018Co-Authors: Mohamedridha Barbouche, Qubo Chen, Marco Carbone, Imen Benmustapha, Zakera Shums, Mehdi Trifa, Federica Malinverno, Francesca Bernuzzi, Haiyan ZhangAbstract:Hyper-immunoglobulin M syndrome is an X-linked primary Immunodeficiency Disease caused by mutations in the CD40 ligand gene. The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary cholangitis. In the present study, we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M syndrome. Serum, liver-related and liver-not-related autoantibodies IgG, IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients (8 males and 5 females, aged 1-12 years) with hyper-immunoglobulin M syndrome during 1995-2012 and, as controls, 21 age- and gender-matched blood donors. The level of IgM antibody against MIT3 was significantly higher in patients than in controls (35.8 vs 10.7, P=0.002). Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls (P<0.0001). Twenty-three percent of patients were found to be anti-sp100 antibody positive vs only 0.05% of controls. By immunofluorescence, 92.3% of patients were MIT3 IgM positive vs none of the controls. In conclusion, the IgM class of anti-MIT3 antibodies was shown to be present by both ELISA and immunofluorescence in most of the patients with hyper-immunoglobulin M syndrome. The presence of the hallmark of primary biliary cholangitis, a Disease where the CD40 ligand is a key player, in an Immunodeficiency Disease caused by mutations in the CD40 ligand gene is very intriguing and opens new scenarios in understanding the immune pathogenesis of primary biliary cholangitis.
Lisa S Westerberg - One of the best experts on this subject based on the ideXlab platform.
-
Activation of compensatory pathways via Rac2 in the absence of the Cdc42 effector Wiskott-Aldrich syndrome protein in Dendritic cells.
Small GTPases, 2017Co-Authors: Marisa A. P. Baptista, Lisa S WesterbergAbstract:There is extensive crosstalk between different Rho GTPases, including Cdc42, Rac1, and Rac2, and they can activate or inhibit the activity of each other. Dendritic cells express both Rac1 and Rac2. Due to posttranslational modification of lipid anchors, Rac1 localizes mainly to the plasma membrane whereas Rac2 localizes to the phagosomal membrane where it assembles the NADPH complex. Our recent study of primary Immunodeficiency Disease caused by mutations in the Cdc42 effector Wiskott-Aldrich syndrome protein (WASp) has shed light on the compensatory mechanisms between Rho GTPases and their effector proteins. WASp-deficient dendritic cells have increased localization and activity of Rac2 to the phagosomal membrane and this allows antigen to be presented on MHC class I molecules to activate cytotoxic CD8+ T cells. This study reveals an intricate balance between Rac2 and WASp signaling pathways and provides an example of compensatory pathways in cells devoid of the Cdc42 effector WASp.
-
wiskott aldrich syndrome protein deficiency leads to reduced b cell adhesion migration and homing and a delayed humoral immune response
Blood, 2005Co-Authors: Lisa S Westerberg, Malin Larsson, Samantha J Hardy, Carmen Nunez FernandezAbstract:The Wiskott-Aldrich syndrome protein (WASp) is mutated in the severe Immunodeficiency Disease Wiskott-Aldrich syndrome (WAS). The function of B cells and the physiologic alterations in WAS remain unclear. We show that B cells from WAS patients exhibited decreased motility and had reduced capacity to migrate, adhere homotypically, and form long protrusions after in vitro culture. WASp-deficient murine B cells also migrated less well to chemokines. Upon antigen challenge, WASp-deficient mice mounted a reduced and delayed humoral immune response to both T-cell–dependent and –independent antigens. This was at least in part due to deficient migration and homing of B cells. In addition, the germinal center reaction was reduced in WASp-deficient mice. Thus, WASp is crucial for optimal B-cell responses and plays a pivotal role in the primary humoral immune response.
