Immunological aspects of immunodeficiency diseases part 95

ALPS is a rare disease caused by defective cellular apoptosis. Failure of lymphocytes to undergo apoptosis results in impaired homeostasis of the lymphoid population. Patients develop lymphocytosis, hyperplasia of lymphoid organs (spleen, lymph nodes), hypergammaglobulinemia, and autoimmunity (autoimmune cytopenias, Guillain-Barre syndrome). Peripheral blood and peripheral lymphoid tissues characteristically contain an increased population of TCR αβ positive CD4 and CD8 cells (double negative T cells). Mutations in the FAS-mediated pathway of apoptosis are responsible for most cases. These include mutations of FAS, FAS-ligand, and caspase 10. Caspase 8 deficiency causes impaired CD95-mediated apoptosis as well as a detect in T-, B-, and NK-cell function, manifesting as an immunodeficiency.  Recently, an activating mutation in the NRAS gene encoding a GTP-binding protein with a broad spectrum of signaling functions has been found in other patients with ALPS. Defective, IL-2 withdrawal induced, apoptosis of lymphocytes is a characteristic abnormality in these patients.