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DECIPHERING THE MECHANISM OF IMMUNE DYSFUNCTION IN VICI SYNDROME.

febrero 17, 2021

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Doctoral Thesis / Dissertation from the year 2015 in the subject Medicine – Human Genetics, grade: 1, University of Rome La Sapienza (University of Rome La Sapienza), course: Clinical Immunology, language: English, abstract: Vici syndrome is a complex multisystem disorder characterized by congenital malformations of the brain, cataracts, skin hypopigmentation, progressive damage of cardiac function and muscle, immune deficiency. Affected children do not respond to vaccination, have low levels of antibodies in the blood and suffering from severe and frequent infections. The disease is caused by a mutation of the gene EPG5, which encodes a protein essential for the trafficking and function of intracellular vesicles. Cells use vesicles to eliminate uwanted material and remove dead cells. The unwanted material is incorporated into a vesicle and then merged with lysosomes containing proteins that digest the contents to be eliminated (autophagy). This system is essential already during the embryonic stage and then for life. Therefore, its failure causes a disease involving various organs and systems. Since infections are frequent in patients with Vici Syndrome, we think that EPG5 plays a role in the immune system:In this project i propose to assess whether EPG5 is necessary for cells to capture and degrade microorganisms and foreign particles, a necessary step to start the immune reaction. To do this i use cells from patients and healthy controls with fluorescent molecules to study the formation and trafficking of vesicles and evaluate the activation of immune cells by measuring the levels of antibodies and cytokines.Other metabolic diseases and multisystem syndromes, often also associated with immunodeficiency, are in fact caused by genes involved in trafficking, merge or release of vesicles in the cell. My study is a prototype, intended to clarify the underlying mechanisms of a defect in a specific immune complex disease. The results will be used to develop t
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