Jurnal Internasional Defek sel-T pada pasien dengan mutasi germline ARPC1B menyebabkan gabungan imunodefisiensi

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Jurnal Internasional Defek sel-T pada pasien dengan mutasi germline ARPC1B menyebabkan gabungan imunodefisiensi

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ARPC1B is a key factor for the assembly and maintenance of ARP2 / 3 complexes involved in actin branching from existing filaments. Germline biolytic mutations in ARPC1B were recently described in 6 patients with a clinical picture of combined immunodeficiency (CID), the neutrophils and platelets but not T lymphocytes studied. We hypothesize that ARPC1B deficiency can also cause cytoskeleton and functional defects in T cells. We have identified bialliic mutations at ARPC1B in 6 patients not associated with early onset disease characterized by severe infection, autoimmune manifestations, and thrombocytopenia. Immunological features including T-cell lymphopenia, low naive T cell counts, and hyper-immunoglobulin E. Changes in the protein structure of ARPC1B caused a low / no expression by flow cytometry and confocal microscopy. This molecular defect is associated with the inability of T cells derived from patients to extend the rich actin lamellipodia in T-cell receptor (TCR) stimulation and to assemble immunological synapses. Deficient-ARPC1B T cells additionally show TCR-mediated proliferation disorders and migrations directed at SDF1-α. Gene transfer ARPC1B in T cells of patients using lentiviral vectors restores ARPC1B expression and T cell proliferation in vitro. In 2 of the patients, in vivo somatic reversion returned ARPC1B expression in lymphocyte fraction and was associated with oblique TCR repertoire. In 1 revertant patient, CD8 memory + 1945-1910 T cells expressing normal levels of ARPC1B show increased T cell migration. ARPC1B deficiency inherited therefore changes the dynamics and cytoseletal function of T cells, contributing to the clinical features of the CID. ] Download Journal Here

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