A5055945749- Immunodeficiency and Autoimmune Disorders
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Cell Adhesion Molecules Research
- Blood disorders and treatments
- Genetics and Neurodevelopmental Disorders
- T-cell and B-cell Immunology
- Autoimmune and Inflammatory Disorders Research
- CAR-T cell therapy research
- Neurogenetic and Muscular Disorders Research
- Cytokine Signaling Pathways and Interactions
- Adenosine and Purinergic Signaling
National Institutes of Health Clinical Center
2021-2024
Australian National University
2021
AIOLOS/IKZF3 is a member of the IKAROS family transcription factors. IKAROS/IKZF1 mutations have been previously associated with different forms primary immunodeficiency. Here we describe novel combined immunodeficiency due to an IKZF3 mutation in presenting T and B cell involvement, Pneumocystis jirovecii pneumonia, and/or chronic lymphocytic leukemia. Patients carrying AIOLOS p.N160S heterozygous variant displayed impaired humoral responses, abnormal development (high percentage CD21low...
Abstract We describe the first cases of germline biallelic null mutations in ARPC5, part Arp2/3 actin nucleator complex, two unrelated patients presenting with recurrent and severe infections, early-onset autoimmunity, inflammation, dysmorphisms. This defect compromises multiple cell lineages functions, when protein expression is reestablished in-vitro, complex conformation functions are rescued. As pathophysiological evaluation, we also show that interleukin (IL)−6 signaling distinctively...
TCF3 is a transcription factor contributing to early lymphocyte differentiation. Germline monoallelic dominant negative and biallelic loss-of-function (LOF) null mutations cause fully penetrant severe immunodeficiency. We identified 8 individuals from 7 unrelated families with LOF variants presenting immunodeficiency incomplete clinical penetrance.
Abstract PAX5 is the master transcription factor controlling B cell identity. In humans, mutations in account for 30% of acute lymphoblastic leukemia (B-ALL) cases. Investigating causal effects has however been difficult due to premature lethality Pax5 −/− mice. Here we describe a novel mouse strain with STOP mutation (Y351*) that produces truncated protein and reduction function, yet still allows some development occur. A population uncommitted multipotent CD19 + B220 − cells develops bone...
Abstract IKZF1 (IKAROS) is essential for normal lymphopoiesis in both humans and mice. Previous Ikzf1 mouse models have demonstrated the dual role B T cell development indicated differential requirements of each zinc finger. Furthermore, mutations are known to cause common variable immunodeficiency patients characterized by a loss cells reduced Ab production. Through N-ethyl-N-nitrosourea mutagenesis, we discovered novel mutant with missense mutation (L132P) finger 1 (ZF1) located DNA...