Alexandra F. Freeman
A5063867007- Immunodeficiency and Autoimmune Disorders
- Immune Cell Function and Interaction
- Blood disorders and treatments
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- Cystic Fibrosis Research Advances
- Fungal Infections and Studies
- Cytomegalovirus and herpesvirus research
- Chronic Lymphocytic Leukemia Research
- Antifungal resistance and susceptibility
- Mycobacterium research and diagnosis
- Hematopoietic Stem Cell Transplantation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Parvovirus B19 Infection Studies
- Tuberculosis Research and Epidemiology
- Pneumocystis jirovecii pneumonia detection and treatment
- Pediatric health and respiratory diseases
- Eosinophilic Esophagitis
- Kawasaki Disease and Coronary Complications
- Immune Response and Inflammation
- Genomics and Rare Diseases
- Polyomavirus and related diseases
- Acute Myeloid Leukemia Research
- Eosinophilic Disorders and Syndromes
- Dermatology and Skin Diseases
National Institutes of Health
2016-2025
National Institute of Allergy and Infectious Diseases
2016-2025
Immune Deficiency Foundation
2024-2025
University of California, San Francisco
2019-2023
University of Cambridge
2023
Western Sydney University
2022
Garvan Institute of Medical Research
2022
Office of Extramural Research
2022
Trinity College Dublin
2022
St. James's Hospital
2022
The hyper-IgE syndrome (or Job's syndrome) is a rare disorder of immunity and connective tissue characterized by dermatitis, boils, cyst-forming pneumonias, elevated serum IgE levels, retained primary dentition, bone abnormalities. Inheritance autosomal dominant; sporadic cases are also found.
Recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE are features some variants combined immunodeficiency. The genetic causes these unknown.We collected longitudinal clinical data on 11 patients from eight families who had recurrent infections. We performed comparative genomic hybridization arrays targeted gene sequencing. Variants predicted loss-of-expression mutations were confirmed by means a quantitative reverse-transcriptase-polymerase-chain-reaction...
The Human Phenotype Ontology (HPO)—a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases—is used by thousands researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions clinical computable disease definitions have made HPO de facto standard for deep phenotyping in field rare disease. HPO's interoperability other ontologies has enabled it to be improve diagnostic accuracy incorporating model organism...
Mendelian analysis of disorders immune regulation can provide insight into molecular pathways associated with host defense and tolerance.We identified three families a dominantly inherited complex cold-induced urticaria, antibody deficiency, susceptibility to infection autoimmunity. Immunophenotyping methods included flow cytometry, serum immunoglobulins autoantibodies, lymphocyte stimulation, enzymatic assays. Genetic studies linkage analysis, targeted Sanger sequencing, next-generation...
Background. Chronic granulomatous disease (CGD) is due to defective nicotinamide adenine dinucleotide phosphate oxidase activity and characterized by recurrent infections with a limited spectrum of bacteria fungi as well inflammatory complications. To understand the impact common severe in CGD, we examined records 268 patients followed at single center over 4 decades. Methods. All had confirmed diagnoses genotype was determined where possible. Medical were excerpted into standard format....
There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors immunity (IEI), a population at risk developing disease 2019. This relevant not only for these patients but also general population, because studies IEIs can unveil key requirements host defense.
Periodontitis is one of the most common human inflammatory diseases, yet mechanisms that drive immunopathology and could be therapeutically targeted are not well defined. Here, we demonstrate an expansion resident memory T helper 17 (TH17) cells in periodontitis. Phenocopying humans, TH17 expanded murine experimental periodontitis through local proliferation. Unlike homeostatic oral cells, which accumulate a commensal-independent interleukin-6 (IL-6)-dependent manner,...
While landmark studies have shown that microbiota activate and educate host immunity, how immune systems shape microbiomes contribute to disease is incompletely characterized. Primary immunodeficiency (PID) patients suffer recurrent microbial infections, providing a unique opportunity address this issue. To investigate the potential influence of immunity on skin microbiome, we examined in with rare monogenic PIDs: hyper-IgE (STAT3-deficient), Wiskott-Aldrich, dedicator cytokinesis 8...
Abstract Cryptococcal meningitis has been described in immunocompromised patients, as well those for whom no immune defect identified. GM-CSF regulates the function of phagocytes and pulmonary alveolar macrophages, critical elements cryptococcal control. We performed clinical histories, immunological evaluation, anticytokine autoantibody screening four current patients with identified tested 103 archived plasma/cerebrospinal fluid samples from meningitis. assessed ability anti–GM-CSF...
Multiple cytokines, including interleukin 6 (IL-6), IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF), signal via the common GP130 cytokine receptor subunit. In this study, we describe a patient with homozygous mutation of IL6ST (encoding p.N404Y) who presented recurrent infections, eczema, bronchiectasis, high IgE, eosinophilia, defective B cell memory, an impaired acute-phase response, as well skeletal abnormalities craniosynostosis. The p.N404Y missense substitution...
Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to large group of RAG-mutated patients, we aimed at characterizing the immunopathology associated each phenotype. Although defective T B cell development is common all phenotypes, patients hypomorphic RAG variants generate cells signatures immune dysregulation produce autoantibodies broad range self-antigens, including type I interferons....