Martin Castelle
A5057966989- Immunodeficiency and Autoimmune Disorders
- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Hemoglobinopathies and Related Disorders
- Blood disorders and treatments
- SARS-CoV-2 and COVID-19 Research
- Prenatal Screening and Diagnostics
- COVID-19 Clinical Research Studies
- Autoimmune and Inflammatory Disorders Research
- Neurogenetic and Muscular Disorders Research
- Diabetes and associated disorders
- Blood groups and transfusion
- Cystic Fibrosis Research Advances
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Glycogen Storage Diseases and Myoclonus
- Acute Lymphoblastic Leukemia research
- Lysosomal Storage Disorders Research
- Long-Term Effects of COVID-19
- Chronic Lymphocytic Leukemia Research
- interferon and immune responses
- Genomics and Rare Diseases
- CAR-T cell therapy research
- Genetic factors in colorectal cancer
Hôpital Necker-Enfants Malades
2016-2025
Assistance Publique – Hôpitaux de Paris
2013-2024
Université Paris Cité
2012-2024
Vall d'Hebron Institut de Recerca
2020-2024
Inserm
2023
Sorbonne Paris Cité
2019-2023
Centre de Référence Déficits Immunitaires Héréditaires
2023
Weatherford College
2023
Hôpital de la Timone
2022
Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
2020
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for some inherited disorders, including selected primary immunodeficiencies (PIDs). In the absence of well-matched donor, HSCT from haploidentical family donor (HIFD) may be considered. adult recipients high-dose post-transplant cyclophosphamide (PTCY) increasingly used to mitigate risks graft failure and graft-versus-host disease (GVHD). However, data on use PTCY in children (and especially those...
Abstract The paradigm type I interferonopathy Aicardi-Goutières syndrome (AGS) is most typically characterized by severe neurological involvement. AGS considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a chronic enhancement of interferon signaling, JAK1/2 inhibition has been trialed in AGS, with clear improvements cutaneous and systemic disease manifestations. Contrastingly, treatment efficacy at the level system less conclusive. Here, we...
Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes sometimes T NK lymphocytes. Persistence of EBV-infected results in severe lymphoproliferative disorders (LPDs). Diagnosis EBV-driven or cell LPD chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects expressing EBV-encoded small RNAs (EBERs), allowing rapid identification among PBMCs. B, T, and/or were detectable various...
We describe an unvaccinated child at risk for life-threatening COVID-19 due to inherited deficiency of IRF9, which governs ISGF-3-dependent responses type I and III interferons (IFN). She was admitted, with a high nasal SARS-CoV-2 load on day 1 upper respiratory tract infection. viremic 2 received casirivimab imdevimab. Her clinical manifestations viremia disappeared days 3 4, respectively. Circulating virus induced the expression IFN-stimulated genes in leukocytes 1, whereas secretion blood...
Patients with inherited CARMIL2 or CD28 deficiency have defective T cell signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three isoforms is produced functional across leukocyte subsets. Tested mutant alleles from 89 patients 52 families impair canonical NF-κB not AP-1 NFAT activation in cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient display recalcitrant warts low blood counts CD4+ CD8+ memory TREGs. Unlike...
In the human genome, about 750 genes contain one intron excised by minor spliceosome. This spliceosome comprises its own set of snRNAs, among which U4atac. Its noncoding gene, RNU4ATAC, has been found mutated in Taybi-Linder (TALS/microcephalic osteodysplastic primordial dwarfism type 1), Roifman (RFMN), and Lowry-Wood (LWS) syndromes. These rare developmental disorders, whose physiopathological mechanisms remain unsolved, associate ante- post-natal growth retardation, microcephaly, skeletal...
Abstract In sickle cell disease (SCD), the β6 Glu→Val substitution in β-globin leads to red blood sickling. The transplantation of autologous, genetically modified hematopoietic stem and progenitor cells (HSPCs) is a promising treatment option for patients with SCD. We completed Phase I/II open-label clinical trial (NCT03964792) SCD using lentiviral vector (DREPAGLOBE) expressing potent anti-sickling β-globin. primary endpoint was evaluate short-term safety secondary endpoints included...
Abstract Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3‐methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely unaffected patients virtual absence of development. Muscular hypo‐ hypertonia, movement disorder progressive brain atrophy are frequently reported. We present foetal, peri‐ neonatal features 31 patients, which five previously unreported, using newly developed clinical severity scoring...
Glycogenosis type Ib (GSD1B) causes not only hypoglycemia but also infections and "Crohn's disease like" inflammatory bowel (IBD) that can significantly impair patient's quality of life. We retrospectively evaluated infectious digestive complications in 9 French patients (3 girls, 6 boys) diagnosed at 0.8 years on average, with a mean follow-up 19.1 years. Infections occurred earlier than IBD, ages 1.7 3.8 years, respectively. The number acute hospitalizations was 0.7/year due to (0.4/year)...
Epstein–Barr virus (EBV) can infect smooth muscle cells causing tumors (SMTs) or leiomyoma. Here, we report a patient with heterozygous 22q11.2 deletion/DiGeorge syndrome who developed unique, broad, and lethal susceptibility to EBV characterized by EBV-infected T B disseminated EBV+SMT. The also harbored homozygous missense mutation (p.V140G) in TNFSF9 coding for CD137L/4-1BBL, the ligand of cell co-stimulatory molecule CD137/4-1BB, whose deficiency predisposes infection. We show that...
Pulmonary hypertension is a rare but important cause of mortality after haematopoietic stem cell transplantation (HSCT) in children. This complication poorly characterised the literature. We report here series children who developed pulmonary HSCT.Between January 2008 and December 2015, we retrospectively analysed 366 underwent HSCT (age range 0.5-252 months; median 20.3 months). During post-HSCT course, echocardiography scans motivated by respiratory symptoms identified 31 patients with...
Abstract Mucopolysaccharidosis type I-H (MPS I-H) is a rare lysosomal storage disorder caused by α-L-Iduronidase deficiency. Early haematopoietic stem cell transplantation (HSCT) the sole available therapeutic option to preserve neurocognitive functions. We report long-term follow-up (median 9 years, interquartile range 8–16.5) for 51 MPS patients who underwent HSCT between 1986 and 2018 in France. 4 died from complications of one disease progression. Complete chimerism normal activity were...
Introduction: Current international guidelines strongly recommend catheter removal in case of S. aureus central-line associated bloodstream infection (CLASBI), but a salvage strategy may be considered children given age-related specificities. No data is available regarding the outcome this children. This study aims to evaluate with CLABSI, and determine treatment failure rates risk factors. Methods: We retrospectively analyzed for all <18 years having CLABSI on long-term central venous...
Methicillin-resistant staphylococcal infections are a global burden. Area under the serum concentration-time curve to minimum inhibitory concentration (AUC/MIC) ratio is pharmacokinetic (PK) parameter that best predicts vancomycin efficacy. Its therapeutic range narrow, difficult achieve because of wide intersubject variability, especially in children, and not routinely targeted since AUC rarely available. We investigated if an early Bayesian dose adjustment would increase rate target...