Showing papers by "Jennifer M. Puck published in 2021"
University of New South Wales1, Garvan Institute of Medical Research2, Kuwait University3, Boston Children's Hospital4, Icahn School of Medicine at Mount Sinai5, University of Antioquia6, National Institutes of Health7, Ludwig Maximilian University of Munich8, Tokyo Medical and Dental University9, Paris Diderot University10, University of Paris11, French Institute of Health and Medical Research12, University of California, San Francisco13, University of Helsinki14, Sheba Medical Center15, Children's Hospital of Philadelphia16, Allen Institute for Artificial Intelligence17, Katholieke Universiteit Leuven18
TL;DR: The most recent updated classification of inborn errors of immunity/primary immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee, was published in January 2020 as mentioned in this paper.
Abstract: The most recent updated classification of inborn errors of immunity/primary immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee, was published in January 2020. Within days of completing this report, it was already out of date, evidenced by the frequent publication of genetic variants proposed to cause novel inborn errors of immunity. As the next formal report from the IUIS Expert Committee will not be published until 2022, we felt it important to provide the community with a brief update of recent contributions to the field of inborn errors of immunity. Herein, we highlight studies that have identified 26 additional monogenic gene defects that reach the threshold to represent novel causes of immune defects.
144 citations
TL;DR: Newborn screening for severe combined immunodeficiency, the most profound form of primary immune system defects, has long been recognized as a measure that would decrease morbidity and improve outcomes by helping patients avoid devastating infections and receive prompt immune-restoring therapy as discussed by the authors.
Abstract: Newborn screening for severe combined immunodeficiency, the most profound form of primary immune system defects, has long been recognized as a measure that would decrease morbidity and improve outcomes by helping patients avoid devastating infections and receive prompt immune-restoring therapy The T-cell receptor excision circle test, developed in 2005, proved to be successful in pilot studies starting in the period 2008 to 2010, and by 2019 all states in the United States had adopted versions of it in their public health programs Introduction of newborn screening for severe combined immunodeficiency, the first immune disorder accepted for population-based screening, has drastically changed the presentation of this disorder while providing important lessons for public health programs, immunologists, and transplanters
50 citations
University of California, San Francisco1, University of Calgary2, Baylor College of Medicine3, George Washington University4, Children's National Medical Center5, Boston Children's Hospital6, University of Washington7, Stanford University8, Nationwide Children's Hospital9, University of Rochester10, University of Texas at Dallas11, University of Pittsburgh12, Washington University in St. Louis13, Columbia University14, University of California, Los Angeles15, University of Pennsylvania16, Cincinnati Children's Hospital Medical Center17, University of Cincinnati18, Northwestern University19, University of Utah20, University of Manitoba21, Alfred I. duPont Hospital for Children22, University of Wisconsin-Madison23, Rutgers University24, University of Alabama at Birmingham25, Mayo Clinic26, University of Southern California27, Cardinal Glennon Children's Hospital28, Emory University29, University of Tennessee Health Science Center30, Johns Hopkins University31, University of South Florida32, Memorial Sloan Kettering Cancer Center33, University of British Columbia34, Lucile Packard Children's Hospital35, Westchester Medical Center36, University of Minnesota37, University of Michigan38, Louisiana State University39, Duke University40, National Institutes of Health41, Université de Montréal42, Medical College of Wisconsin43, Harvard University44
TL;DR: Infants with SCID diagnosed due to FH had lower rates of infection and proceeded to HSCT more quickly than did those diagnosed via NBS and/or FH and there was no consensus among PIDTC survey respondents as to the best setting for pre-HSCT management.
Abstract: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children with severe combined immunodeficiency (SCID) in a prospective natural history study of hematopoietic stem cell transplant (HSCT) outcomes over the last decade. Despite newborn screening (NBS) for SCID, infections occurred prior to HSCT. This study’s objectives were to define the types and timing of infection prior to HSCT in patients diagnosed via NBS or by family history (FH) and to understand the breadth of strategies employed at PIDTC centers for infection prevention. We analyzed retrospective data on infections and pre-transplant management in patients with SCID diagnosed by NBS and/or FH and treated with HSCT between 2010 and 2014. PIDTC centers were surveyed in 2018 to understand their practices and protocols for pre-HSCT management. Infections were more common in patients diagnosed via NBS (55%) versus those diagnosed via FH (19%) (p = 0.012). Outpatient versus inpatient management did not impact infections (47% vs 35%, respectively; p = 0.423). There was no consensus among PIDTC survey respondents as to the best setting (inpatient vs outpatient) for pre-HSCT management. While isolation practices varied, immunoglobulin replacement and antimicrobial prophylaxis were more uniformly implemented. Infants with SCID diagnosed due to FH had lower rates of infection and proceeded to HSCT more quickly than did those diagnosed via NBS. Pre-HSCT management practices were highly variable between centers, although uses of prophylaxis and immunoglobulin support were more consistent. This study demonstrates a critical need for development of evidence-based guidelines for the pre-HSCT management of infants with SCID following an abnormal NBS. NCT01186913
31 citations
Children's Hospital of Philadelphia1, Children's Memorial Hospital2, Northwestern University3, Georgia State University4, University of California, San Francisco5, Yale University6, Medical College of Wisconsin7, University of Pennsylvania8, University of California, Berkeley9, Laboratory of Molecular Biology10, University of Alabama at Birmingham11, Baylor College of Medicine12, Boston Children's Hospital13, Baylor University14
TL;DR: The pioneer transcription factor (TF) PU.1 controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing non-pioneer TFs to enter otherwise inaccessible genomic sites as mentioned in this paper.
Abstract: The pioneer transcription factor (TF) PU.1 controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing nonpioneer TFs to enter otherwise inaccessible genomic sites. PU.1 deficiency fatally arrests lymphopoiesis and myelopoiesis in mice, but human congenital PU.1 disorders have not previously been described. We studied six unrelated agammaglobulinemic patients, each harboring a heterozygous mutation (four de novo, two unphased) of SPI1, the gene encoding PU.1. Affected patients lacked circulating B cells and possessed few conventional dendritic cells. Introducing disease-similar SPI1 mutations into human hematopoietic stem and progenitor cells impaired early in vitro B cell and myeloid cell differentiation. Patient SPI1 mutations encoded destabilized PU.1 proteins unable to nuclear localize or bind target DNA. In PU.1-haploinsufficient pro-B cell lines, euchromatin was less accessible to nonpioneer TFs critical for B cell development, and gene expression patterns associated with the pro- to pre-B cell transition were undermined. Our findings molecularly describe a novel form of agammaglobulinemia and underscore PU.1's critical, dose-dependent role as a hematopoietic euchromatin gatekeeper.
18 citations
TL;DR: In this article, a systematic literature review highlighted the diverse terminology in severe combined immunodeficiency (SCID) NBS programs and found uniform terminology to be lacking in definitions of disease targets, sensitivity, and specificity required for comparisons across programs.
Abstract: Background Public health newborn screening (NBS) programs continuously evolve, taking advantage of international shared learning. NBS for severe combined immunodeficiency (SCID) has recently been introduced in many countries. However, comparison of screening outcomes has been hampered by use of disparate terminology and imprecise or variable case definitions for non-SCID conditions with T-cell lymphopenia. Objectives This study sought to determine whether standardized screening terminology could overcome a Babylonian confusion and whether improved case definitions would promote international exchange of knowledge. Methods A systematic literature review highlighted the diverse terminology in SCID NBS programs internationally. While, as expected, individual screening strategies and tests were tailored to each program, we found uniform terminology to be lacking in definitions of disease targets, sensitivity, and specificity required for comparisons across programs. Results The study's recommendations reflect current evidence from literature and existing guidelines coupled with opinion of experts in public health screening and immunology. Terminologies were aligned. The distinction between actionable and nonactionable T-cell lymphopenia among non-SCID cases was clarified, the former being infants with T-cell lymphopenia who could benefit from interventions such as protection from infections, antibiotic prophylaxis, and live-attenuated vaccine avoidance. Conclusions By bringing together the previously unconnected public health screening community and clinical immunology community, these SCID NBS deliberations bridged the gaps in language and perspective between these disciplines. This study proposes that international specialists in each disorder for which NBS is performed join forces to hone their definitions and recommend uniform registration of outcomes of NBS. Standardization of terminology will promote international exchange of knowledge and optimize each phase of NBS and follow-up care, advancing health outcomes for children worldwide.
12 citations
TL;DR: In this paper, the authors focus on the diagnostic evaluation and management of cases in which abnormal TRECs are associated with variants of T cell lymphopenia in the absence of a genetically defined form of typical or atypical SCID.
Abstract: Newborn screening efforts focusing on the quantification of T cell receptor excision circles (TRECs), as a biomarker for abnormal thymic production of T cells, have allowed for the identification and definitive treatment of severe combined immunodeficiency (SCID) in asymptomatic neonates. With the adoption of TREC quantification in Guthrie cards across the USA and abroad, typical, and atypical SCID constitutes only ~ 10% of cases identified with abnormal TRECs associated with T cell lymphopenia. Several other non-SCID-related conditions may be identified by newborn screening in a term infant. Thus, it is important for physicians to recognize that other factors, such as prematurity, are often associated with low TRECs initially, but often improve with age. This paper focuses on a challenge that immunologists face: the diagnostic evaluation and management of cases in which abnormal TRECs are associated with variants of T cell lymphopenia in the absence of a genetically defined form of typical or atypical SCID. Various syndromes associated with T cell impairment, secondary forms of T cell lymphopenia, and idiopathic T cell lymphopenia are identified using this screening approach. Yet there is no consensus or guidelines to assist in the evaluation and management of these newborns, despite representing 90% of the patients identified, resulting in significant work for the clinical teams until a diagnosis is made. Using a case-based approach, we review pearls relevant to the evaluation of these newborns, as well as the management dilemmas for the families and team related to the resolution of genetic ambiguities.
10 citations
TL;DR: In this article, the authors used high-throughput sequencing to study composition and diversity of the T-cell receptor β (TRB) repertoire in 27 infants with SCID at 3, 6, and 12 months and yearly posttreatment(s).
Abstract: Background Development of a diverse T-cell receptor β (TRB) repertoire is associated with immune recovery following hematopoietic cell transplantation (HCT) for severe combined immunodeficiency (SCID). High-throughput sequencing of the TRB repertoire allows evaluation of clonotype dynamics during immune reconstitution. Objectives We investigated whether longitudinal analysis of the TRB repertoire would accurately describe T-cell receptor diversity and illustrate the quality of T-cell reconstitution following HCT or gene therapy for SCID. Methods We used high-throughput sequencing to study composition and diversity of the TRB repertoire in 27 infants with SCID at 3, 6, and 12 months and yearly posttreatment(s). Total RNA from peripheral blood was used as template to amplify TRB rearrangements. Results TRB sequence analysis showed poor diversity at 3 months, followed by significant improvement by 6 months after cellular therapies. Kinetics of development of TRB diversity were similar in patients with a range of underlying gene defects. However, in patients with RAG and DCLRE1C defects, HCT with no conditioning or immune suppression only resulted in lower diversity than did HCT with conditioning. HCT from a matched donor correlated with higher diversity than did HCT from a mismatched donor. Naive CD4+ T-cell count at 6 months post-HCT correlated with higher TRB diversity. A Shannon index of diversity of 5.2 or lower 3 months after HCT predicted a need for a second intervention. Conclusions TRB repertoire after hematopoietic cell therapies for SCID provides a quantitative and qualitative measure of diversity of T-cell reconstitution and permits early identification of patients who may require a second intervention.
5 citations
TL;DR: In this article, a newborn screening for severe combined immunodeficiency (SCID) has developed from the realization that infants affected with SCID require prompt diagnosis and treatment to avoid fatal infectious complications.
Abstract: Newborn screening for severe combined immunodeficiency (SCID) has developed from the realization that infants affected with SCID require prompt diagnosis and treatment to avoid fatal infectious complications. Screening DNA from infant dried blood spots for T-cell receptor excision circles (TRECs), byproducts of normal antigen-receptor gene rearrangement, has proven to be a reliable method to identify infants with SCID and other serious T lymphocyte defects before the onset of serious infections. The experience of the SCID newborn screening program in California after screening over 3 million infants demonstrates the effectiveness of this measure.
5 citations
3 citations
University of California, San Francisco1, University of Calgary2, Baylor College of Medicine3, Children's National Medical Center4, George Washington University5, Boston Children's Hospital6, University of Washington7, Stanford University8, Nationwide Children's Hospital9, University of Rochester10, University of Texas at Dallas11, University of Pittsburgh12, Washington University in St. Louis13, Columbia University14, University of California, Los Angeles15, University of Pennsylvania16, Cincinnati Children's Hospital Medical Center17, University of Cincinnati18, Northwestern University19, University of Utah20, University of Manitoba21, Alfred I. duPont Hospital for Children22, University of Wisconsin-Madison23, Rutgers University24, University of Alabama at Birmingham25, Mayo Clinic26, University of Southern California27, Cardinal Glennon Children's Hospital28, Emory University29, University of Tennessee Health Science Center30, University of South Florida31, Johns Hopkins University32, Memorial Sloan Kettering Cancer Center33, University of British Columbia34, Lucile Packard Children's Hospital35, Westchester Medical Center36, University of Minnesota37, University of Michigan38, Louisiana State University39, Duke University40, National Institutes of Health41, Université de Montréal42, Medical College of Wisconsin43, Harvard University44
TL;DR: A Correction to this paper has been published: https://doi.org/10.1007/s10875-020-00917-0
Abstract: A Correction to this paper has been published: https://doi.org/10.1007/s10875-020-00917-0
TL;DR: In this paper, a survey was designed and distributed to families of patients with SCID to understand their perceptions of pre-treatment counseling and understanding of durability of HCT/GT are poorly understood.