A5037652877- Immune Cell Function and Interaction
- Acute Lymphoblastic Leukemia research
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Kawasaki Disease and Coronary Complications
- Neuroblastoma Research and Treatments
- COVID-19 Clinical Research Studies
- Autoimmune and Inflammatory Disorders Research
- Pancreatic function and diabetes
- COVID-19 Impact on Reproduction
- SARS-CoV-2 and COVID-19 Research
- Adolescent and Pediatric Healthcare
- Diabetes and associated disorders
- Immunotherapy and Immune Responses
- Inflammasome and immune disorders
- Long-Term Effects of COVID-19
- Xenotransplantation and immune response
- Virus-based gene therapy research
- Mechanical Circulatory Support Devices
- Polyamine Metabolism and Applications
- Pneumonia and Respiratory Infections
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Research Studies
- Venous Thromboembolism Diagnosis and Management
- IL-33, ST2, and ILC Pathways
Children's Hospital of Philadelphia
2015-2024
University of Pennsylvania
2001-2024
Philadelphia University
2013-2023
Office of Infectious Diseases
2013-2020
AID Atlanta
2020
Children's Cancer Institute Australia
2015
Lankenau Institute for Medical Research
2015
Brigham and Women's Hospital
2013
Baylor College of Medicine
2013
Pediatrics and Genetics
2009
Objective To provide guidance on the management of multisystem inflammatory syndrome in children (MIS‐C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late course severe acute respiratory coronavirus 2 (SARS–CoV‐2) infection, to recommendations for with hyperinflammation during disease 2019 (COVID‐19), acute, infectious phase SARS–CoV‐2 infection. Methods A multidisciplinary task force was convened American College Rheumatology (ACR) MIS‐C...
Objective To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS‐C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late course severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2) infection. Recommendations are also provided for children with hyperinflammation during disease 2019 (COVID‐19), acute, infectious phase SARS–CoV‐2 Methods The Task Force was composed 9 pediatric rheumatologists adult...
BACKGROUND. Initial reports from the severe acute respiratory coronavirus 2 (SARS–CoV-2) pandemic described children as being less susceptible to disease 2019 (COVID-19) than adults. Subsequently, a and novel pediatric disorder termed multisystem inflammatory syndrome in (MIS-C) emerged. We report on unique hematologic immunologic parameters that distinguish between COVID-19 MIS-C provide insight into pathophysiology.
We present a series of 6 critically ill children with multisystem inflammatory syndrome in children. Key findings this include fever, diarrhea, shock, and variable presence rash, conjunctivitis, extremity edema, mucous membrane changes.
To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS-C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late course SARS-CoV-2 infection. Recommendations are also provided for children with hyperinflammation during COVID-19, acute, infectious phase infection.The Task Force is composed 9 pediatric rheumatologists 2 adult rheumatologists, cardiologists, disease specialists, 1 critical care physician....
Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present Multisystem Inflammatory Syndrome Children (MIS-C) that can lead to vascular complications shock, but rarely death. The immune features MIS-C compared pediatric or adult remain poorly understood. We analyzed peripheral blood responses hospitalized infected patients (pediatric COVID-19) MIS-C. had patterns T cell-biased...
Abstract The ability to utilize preclinical models predict the clinical toxicity of chimeric antigen receptor (CAR) T cells in solid tumors is tenuous, thereby necessitating development and evaluation gated systems. Here we found that murine GD2 CAR-T cells, specific for tumor-associated GD2, induce fatal neurotoxicity a costimulatory domain-dependent manner. Meanwhile, human B7H3 exhibit efficacy neuroblastoma. Seeking better CAR, generated SynNotch CAR-T, GD2-B7H3, recognizing as gate...
Abstract Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, a small proportion developing disease multisystem inflammatory in (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated SARS-CoV-2 adults but not studied the pediatric population. We hypothesized that complement activation plays an important role and sought to understand if TMA was present these patients. enrolled 50 hospitalized...
Multi-system Inflammatory Syndrome in Children (MIS-C) is a major complication of Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) infection pediatric patients. Weeks after an often mild or asymptomatic initial with SARS-CoV-2 children may present severe shock-like picture and marked inflammation. MIS-C varying degrees cardiovascular hyperinflammatory symptoms. Here we perform comprehensive analysis the plasma proteome more than 1400 proteins SARS-CoV-2. We hypothesize that would reflect...
To study the biology and identify markers of severe cytokine release syndrome (CRS) immune effector cell-associated neurotoxicity (ICANS) in children after chimeric antigen receptor T-cell (CAR T) treatment.We used comprehensive proteomic profiling to measure over 1,400 serum proteins at multiple serial timepoints a cohort patients with B-cell acute lymphoblastic leukemia treated CD19-targeted CAR T CTL019 on two clinical trials.We identified fms-like tyrosine kinase 3 (FLT3) mast cell...
Abstract IL-2-deficient (IL-2−/−) mice develop disorders of the hemopoietic and immune systems characterized by anemia, lymphocytic hyperplasia, colitis. The mechanisms responsible for these abnormalities remain unclear. To investigate underlying basis autoimmunity, particular role commensal gut flora in initiation colitis, IL-2 development intestinal intraepithelial lymphocytes (iIEL), we evaluated IL-2−/− reared maintained under gnotobiotic (germfree) conditions. By 8 wk age, 80% (20 25)...
Abstract Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody responses in children remain poorly characterized. Here, we show that pediatric patients with multisystem inflammatory syndrome (MIS-C) possess higher SARS-CoV-2 spike immunoglobulin G (IgG) titers compared those severe coronavirus disease 2019, likely reflecting a longer time since the onset of infection MIS-C patients.
Immune-mediated lung injury and systemic hyperinflammation are characteristic of severe critical coronavirus disease 2019 (COVID-19) in adults. Although the majority acute respiratory syndrome 2 infections pediatric populations result minimal or mild COVID-19 phase infection, a small subset children develop even this with concomitant inflammation that may benefit from immunomodulation. Therefore, guidance is needed regarding immunomodulatory therapies setting COVID-19. This document does not...
Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted glycolipid-reactive lymphocytes with important roles in host immunity to cancer. iNKT indirectly participate antitumor responses by inducing dendritic cell maturation and producing cytokines that promote tumor clearance CD8+ NK cells. Although thereby act as potent cellular adjuvants, it is less clear whether they directly control the growth tumors. To gain insights into direct contribution immune surveillance, we...
There are no proven safe and effective therapies for children who develop life-threatening complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS-CoV-2, but theoretical risks.We present the first report CP disease 2019 (COVID-19), providing data on four pediatric patients distress syndrome. We measured donor antibody levels recipient response prior to following infusion. Infusion was not...
ABSTRACT Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present Multisystem Inflammatory Syndrome Children (MIS-C) that can lead to vascular complications shock, but rarely death. The immune features MIS-C compared pediatric or adult remain poorly understood. We analyzed peripheral blood responses hospitalized infected patients (pediatric COVID-19) MIS-C. had patterns T...
To examine the immune response to class I—deficient allogeneic tissue, we used β2-microglobulin-deficient mice as graft donors. These lack cell surface I major histocompatibility complex antigen expression. Pancreatic islet allografts from I-deficient donors survived indefinitely in a majority of fully BALB/c recipients. In contrast, host recognition was unnecessary for prompt destruction skin autoimmune damage transplanted pancreatic grafts nonobese diabetic mice. studies provide evidence...
Abstract Although the identity of T cells involved in protection against Mycobacterium tuberculosis (Mtb) humans remain unknown, patients with pulmonary (TB) have reduced numbers Mtb-reactive, Vγ9+/Vδ2+ their blood and lungs. Here we determined whether this γδ loss is a consequence Mtb Ag-mediated activation-induced cell death (AICD). Using DNA polymerase-mediated dUTP nick translation labeling assay, 5% or less freshly isolated CD4+ αβ from normal healthy individuals TB were apoptotic....
Abstract Chimeric antigen receptor (CAR) T-cells directed against CD19 have drastically altered outcomes for children with relapsed and refractory acute lymphoblastic leukemia (r/r ALL). Pediatric patients r/r ALL treated CAR-T are at increased risk of both cytokine release syndrome (CRS) sepsis. We sought to investigate the biologic differences between CRS sepsis develop predictive models which could accurately differentiate from time critical illness. identified 23 different cytokines that...
ABSTRACT SARS-CoV-2 antibody responses in children remain poorly characterized. Here, we show that pediatric patients with multisystem inflammatory syndrome (MIS-C) possess higher spike IgG titers compared to those severe coronavirus disease 2019 (COVID-19), likely reflecting a longer time since onset of infection MIS-C patients.