A5082644654- Immunodeficiency and Autoimmune Disorders
- Blood disorders and treatments
- Immune Cell Function and Interaction
- Platelet Disorders and Treatments
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- SARS-CoV-2 and COVID-19 Research
- Epigenetics and DNA Methylation
- Tumors and Oncological Cases
- Single-cell and spatial transcriptomics
- COVID-19 Clinical Research Studies
- Heparin-Induced Thrombocytopenia and Thrombosis
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Vaccine Coverage and Hesitancy
- Diabetes and associated disorders
- Biosensors and Analytical Detection
- Erythrocyte Function and Pathophysiology
- Neurogenetic and Muscular Disorders Research
- Lymphoma Diagnosis and Treatment
- Infant Nutrition and Health
- Blood properties and coagulation
- Immune responses and vaccinations
- Pneumocystis jirovecii pneumonia detection and treatment
- Vascular Malformations and Hemangiomas
Centre for Biomedical Network Research on Rare Diseases
2020-2025
Hospital Universitario La Paz
2015-2025
Hospital La Paz Institute for Health Research
2014-2023
Instituto de Salud Carlos III
2023
Leiden University Medical Center
2020
Common variable immunodeficiency (CVID) is the most frequent symptomatic primary characterized by recurrent infections, hypogammaglobulinemia and poor response to vaccines. Its diagnosis made based on clinical immunological criteria, after exclusion of other diseases that can cause similar phenotypes. Currently, less than 20% cases CVID have a known underlying genetic cause. We analyzed whole-exome sequencing copy number variants data 36 children adolescents diagnosed with healthy relatives...
Heterotrimers composed of B cell CLL/lymphoma 10 (BCL10), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain-containing (CARD) family adaptors play a role in NF-κB activation have been shown to be involved both the innate adaptive arms immunity murine models. Moreover, individuals with inherited defects MALT1, CARD9, CARD11 present immunological clinical phenotypes. Here, we characterized case autosomal-recessive, complete BCL10...
The rapid development of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to design accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with BNT162b2 vaccine has demonstrated provide 95% efficacy individuals, effects second dose individuals who previously recovered from natural SARS-CoV-2 infection not investigated detail. In this study, we characterize spike-specific...
Abstract Common variable immunodeficiency (CVID), the most frequent primary characterized by loss of B-cell function, depends partly on genetic defects, and epigenetic changes are thought to contribute its aetiology. Here we perform a high-throughput DNA methylation analysis this disorder using pair CVID-discordant MZ twins show predominant gain in CVID B cells with respect those from healthy sibling critical lymphocyte genes, such as PIK3CD , BCL2L1 RPS6KB2 TCF3 KCNN4 . Individual confirms...
Abstract Common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, displays impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance ample phenotypic expressivity in CVID suggest participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for are uniquely valuable studying contribution epigenetics to disease. Here, we generate a single-cell epigenomics transcriptomics census...
BackgroundPredominantly antibody deficiencies (PADs) are the most prevalent primary immunodeficiencies, but their B-cell defects and underlying genetic alterations remain largely unknown.ObjectiveWe investigated patients with PADs for distribution of 41 blood plasma cell (PC) subsets, including subsets defined by expression distinct immunoglobulin heavy chain subclasses.MethodsBlood samples from 139 PADs, 61 common variable immunodeficiency (CVID), 68 selective IgA deficiency (IgAdef), 10...
Over the last decade, identification of hypomorphic variants in patients previously diagnosed with Common Variable Immunodeficiency (CVID) has led to association milder phenotypes IL2RG gene that are usually related severe combined immunodeficiency. Indeed, several revertant mosaicisms have been described cases gene. Our main objective herein was functional characterization p. (Pro58Thr) variant an adult patient antibody deficiency and moderate CD4+ T cell lymphopenia. Evaluation included a...
X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection and neoplasia (XMEN) disease is caused by hemizygous loss of function (LOF) gene variants in MAGT1. MAGT1 a plasma membrane transporter (Mg2+) that plays relevant role immune responses acts as second messenger intracellular signaling, but also it involved the glycosylation proteins. Here we report two from different families XMEN disease. A de novo variant c.97_98 delinsC affecting one member family three...
Common Variable Immunodeficiency (CVID) is characterized by impaired antibody production and poor terminal differentiation of the B cell compartment, yet its pathogenesis still poorly understood. We first reported occurrence epigenetic alterations in CVID high-throughput methylation analysis CVID-discordant monozygotic twins. Data from a recent whole DNA methylome throughout different stages normal allowed us to design new experimental approach. selected CpG sites for based on two criteria:...
Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide toward the relevant panel and final diagnosis. In this study, we validated algorithm automated (database-supported) gating identification (AGI tool) cell subsets within samples stained with ALOT. A reference database normal peripheral blood (PB, n = 41) bone marrow (BM; 45) analyzed ALOT was constructed, served as a AGI tool automatically...
Introduction Common Variable Immunodeficiency (CVID) is characterized by defective antibody production and hypogammaglobulinemia. Flow cytometry immunophenotyping of blood lymphocytes has become great relevance for the diagnosis classification CVID, due to an impaired differentiation mature post-germinal-center (GC) class-switched memory B-cells (MBC) severely decreased plasmablast/plasma cell (Pb) counts. Here, we investigated in detail pre-GC B-cell maturation compartment CVID patients....
B-cell precursors (BCP) arise from hematopoietic stem cells in bone marrow (BM). Identification and characterization of the different BCP subsets has contributed to understanding normal development. first rearrange their immunoglobulin (Ig) heavy chain (IGH) genes form pre-B-cell receptor (pre-BCR) complex together with surrogate light chains. Appropriate signalling via this pre-BCR is followed by rearrangement Ig genes, resulting formation selection functional BCR molecules. Consecutive...
Background The use of next-generation sequencing in inborn errors immunity (IEI) has considerably increased the identification novel gene variants, many which are identified patients without described clinical phenotype or with variants uncertain pathogenic significance previously genes. Properly designed functional and cellular assays, necessarily accomplished by research-based laboratories, reveal consequences contribute to diagnosis. Activated PI3Kδ syndrome (APDS) is a rare disease that...
Abstract Background Primary antibody deficiencies (PADs) are characterized by hypogammaglobulinemia and impaired B‐cell differentiation. Patients with common variable immunodeficiency (CVID) present severe reductions in at least 2 serum immunoglobulins terminal differentiation of B cells. Most patients CVID do not appear to monogenic defects. Activated phosphoinositide 3‐kinase delta syndrome (APDS), caused gain‐of‐function mutations the PIK3CD gene (p110δ), can a CVID‐like phenotype. Memory...
Common variable immunodeficiency (CVID) is a primary characterized by hypogammaglobulinemia and different degrees of B cell compartment alteration. Memory differentiation requires the orchestrated activation several intracellular signaling pathways that lead to number factors, such as nuclear factor kappa (NF-κB) which, in turn, promote transcriptional programs required for long-term survival. The aim this study was determine if disrupted differentiation, survival cells CVID patients could...
Inborn errors of immunity (IEI) are an expanding group rare diseases whose field has been boosted by next-generation sequencing (NGS), revealing several new entities, accelerating routine diagnoses, the number atypical presentations and generating uncertainties regarding pathogenic relevance novel variants. Research laboratories that diagnose provide support for IEI require accurate, reproducible sustainable phenotypic, cellular molecular functional assays to explore consequences human...
Real world data on the response to SARS-CoV-2 vaccine in patients with immunomediated diseases (IMIDs) treated immunesuppressants is of great interest because may be impaired. The main aim was study humoral and cellular immune after vaccination IMIDs immunosuppressants. secondary describe frequency infections these patients.This an observational including 86 IMIDs. All were biologic or targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs: TNF inhibitors (TNFi), rituximab,...
The rapid development and deployment of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to design accelerated vaccination schedules that have been extremely effective in naïve individuals. While a two-dose immunization regimen with BNT162b2 vaccine has demonstrated provide 95% efficacy individuals, effects second dose individuals who previously recovered from natural SARS-CoV-2 infection not investigated detail. Here we characterized,...
X-linked Agammaglobulinemia is a primary immunodeficiency caused by mutations in BTK, tyrosine kinase essential for B lymphocytes differentiation. Patients usually have very low or absent and are not able to develop humoral specific responses. Here we present boy, diagnosed with XLA due mutation on the promoter region of gene, whose phenotype characterised percentage cells, hypogammaglobulinemia, oscillating neutropenia, antibodies responses some antigens after vaccination IgE-mediated...