Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy

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Murine LRBA deficiency causes CTLA-4 deficiency in Tregs without progression to immune dysregulation

Inherited mutations in lipopolysaccharide-responsive beige-like anchor (LRBA) cause a recessive human immune dysregulation syndrome with memory B-cell and antibody deficiency (common variable immunodeficiency), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL/6 m...

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Immune dysregulation in patients with TRNT1 deficiency

Objective To investigate the pathogenesis of disease in patients with the deficiency of the CCA-adding enzyme tRNA nucleotidyltransferase 1 (TRNT1). The TRNT1 enzyme catalyzes an essential step for tRNA maturation and protein synthesis, however it is largely unknown how abnormalities in this pathway lead to inflammation and immunodeficiency. Patients and Methods: Whole exome sequencing (WES) wa...

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Agammaglobulinaemia despite terminal B-cell differentiation in a patient with a novel LRBA mutation

Mutations in lipopolysaccharide-responsive vesicle trafficking, beach and anchor-containing protein (LRBA) cause immune deficiency and inflammation. Here, we are reporting a novel homozygous mutation in LRBA allele in 7-year-old Omani boy, born to consanguineous parents. He presented with type 1 diabetes, autoimmune haematological cytopenia, recurrent chest infections and lymphocytic interstiti...

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Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity.

Most autosomal genetic causes of childhood-onset hypogammaglobulinemia are currently not well understood. Most affected individuals are simplex cases, but both autosomal-dominant and autosomal-recessive inheritance have been described. We performed genetic linkage analysis in consanguineous families affected by hypogammaglobulinemia. Four consanguineous families with childhood-onset humoral imm...

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Multifocal gastric adenocarcinoma in a patient with LRBA deficiency

BACKGROUND Lipopolysaccharide-responsive, beige-like anchor protein (LRBA) deficiency is characterized by primary immunodeficiency and autoimmunity. Cancer may present another feature of LRBA deficiency. We describe a case history of a young adult with LRBA deficiency and two independent malignancies. METHODS Family-trio whole exome sequencing with unbiased phenotype ontology approach was use...

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ژورنال

عنوان ژورنال: Science

سال: 2015

ISSN: 0036-8075,1095-9203

DOI: 10.1126/science.aaa1663