Navegando por Palavras-chave "Activated Pi3kcd Syndrome"

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    Subpopulações de células B e T foliculares em pacientes com síndrome do PI3KCD ativado (APDS)
    (Universidade Federal de São Paulo (UNIFESP), 2021) Velasco, Helena Fleck [UNIFESP]; Pinto, Maria Isabel De Moraes [UNIFESP]; Universidade Federal de São Paulo
    Introduction: Inborn Immunity Errors are a heterogeneous group of genetic diseases that affect the functioning of the immune system. Activated PI3Kδ syndrome (Activated PI3K delta syndrome - APDS) is one of the new inborn erros of immunity described because of the evolution of molecular biology. APDS is caused by heterozygous gain-of-function mutations in genes encoding the enzyme complex phosphoinositide 3-kinase (PI3K). The main clinical manifestations are pulmonary infections, high susceptibility to virus infections, benign lymphoproliferation and predisposition to lymphoma. Patients with APDS have defects in humoral and cellular immunity and consequently do not respond adequately to vaccines. Objectives: To evaluate follicular B and T cell subpopulations in patients with APDS. To compare laboratory findings with the clinical manifestations of affected patients. To describe from a clinical and laboratory point of view a family with an unprecedented PI3K gain-of-function mutation. Methods: All twelve patients with APDS who were evaluated at the Allergy and Clinical Immunology clinic at UNIFESP were selected. Among these patients, seven belonged to a family that was also described separately for presenting a new genetic variant of APDS, p.529insHEK. Clinical data were collected from all patients and for laboratory evaluation, peripheral blood samples were collected the same patients and 12 controls matched by sex and age. Absolute counts of T, B and NK lymphocytes and percentage of B and follicular T lymphocytes subsets was performed by flow cytometry. Results: Most patients had recurrent respiratory tract infections, pneumonia and bronchiectasis. Some patients also had lymphoproliferation. Compared to controls, patients with APDS had significantly lower numbers of B cells, TCD3, TCD4, TCD8 and CD19. Lower numbers of B lymphocytes appear to be associated with a reduction in the number of memory B cells. Unlike the literature, the patients in the study did not show an increase in transitional B cells. The value of total follicular T cells diverged between the different variants, but all presented a reduced number of follicular T cells 17 (Tfh17). Patients with the new genetic variant of APDS, p.529insHEK presented varied clinical manifestations, however with a similar pattern in infections and in autoimmunity/lymphoproliferation, which confirms the importance of studies of families with rare diseases, especially for a better understanding of this group of disease. Conclusion: Patients with mutations in the PIK3CD gene have varied symptoms but with similar clinical features. The value of total follicular T cells diverged among the different genetic variants, but all presented a reduced number of follicular T cells 17 which may be related to defects in the production of antibodies found in APDS. Patients with the new genetic variant of APDS, p.529insHEK. presented varied clinical manifestations, however with a similar pattern in infections and in autoimmunity/lymphoproliferation, which confirms the importance of studies of families with rare diseases, especially for a better understanding of this group of disease.