LRBA mutations cause autoimmunity, lymphoproliferation and humoral immuneÊdeficiency. We describe a patient affected, since the age of 6 months, by autoimmunity/ autoinflammation including: panniculitis, evolved in gene- ralized lipodystrophy, hypertriglyceridemia, hyperglycemia, diffuse lymphadenopathy, hepatomegaly with hepatic steatosis, splenomegaly, autoimmune neutropenia, hypo- gammaglobulinemia and periodic fever. Exome sequencing revealed two novel heterozygous mutations in LRBA gene. She showed increased CD4:CD8 ratio with elevated memory T cells. Ki67 was increased in CD3, memory CD4 and double negative T cells. FOXP3+ T regulatory cells (Tregs) were present but decreased. LRBA expression was reduced, espe- cially on CD4+ T cells. Levels of CTLA4 in Tregs and the kinetic of its expression in activated T cells were altered with slower upregulation as compared to normal donors and faster downregulation, likely contributing to lymphoproliferation. Autoreactive CD21lowCD38low and activated CD24brightCD38low B cells were high, while memory B cells were reduced, supporting autoimmune manifestations and hypogammaglobuliemia. Rapamycin dramatically re- duced lymphoproliferation although a more targeted therapy would be desirable. Leptin treatment solved the atypical met- abolic manifestations whose cause remains unclear.
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|Titolo:||Lipopolysaccharide-responsive and beige-like anchor (LRBA) protein deficiency manifesting with lypodistrophy and alps-like phenotype treated with leptin and rapamycin|
FLORIS, Matteo [Data Curation]
|Data di pubblicazione:||2016|
|Appare nelle tipologie:||4.2 Abstract in Atti di convegno|