Paroxysmal nocturnal hemoglobinuria decay-accelerating factor

Paroxysmal nocturnal hemoglobinuria (MIM 311770) Acquired defect in biosynthesis of the GPf structures of decay accelerating factor (DAF) and CD59. 

Medof, M.E., Kinoshita, T, Silber, R. and Nussenzweig, V. (1985) Amelioration of lytic abnormalities of paroxysmal nocturnal hemoglobinuria with decay-accelerating factor. Proc. Natl Acad. Sci. U.S.A. 82, 2980-2984. 

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia resulting from a somatic mutation in a multipotent hemopoietic stem cell (reviewed in refs. [115,116]). The abnormal stem cells produce subpopulations of blood cell types that lack all GPI-anchored proteins. The absence of decay-accelerating factor (DAF) and... 

GPI-deficient mammalian cells are viable in tissue culture and many GPI-deficient mutant cell lines have been established. However, GPI deficiency has major consequences at the level of tissues and the whole body. This was revealed in transgenic mouse models in which the PIG-A gene (required for the first step of GPI biosynthesis) was knocked out in specific tissues or in the whole animal. For example, keratinocyte-specific disruption of PIG-A caused abnormal development of skin leading to death of the mutant mice a few days after birth (M. Tarutani, 1997), and disruption of PIG-A in the whole animal resulted in embryos that did not develop beyond day 9 of gestation (M. Nozaki, 1999). A somatic mutation of PIG-A in multipotent hematopoietic human stem cells causes paroxysmal nocturnal hemoglobinuria, an acquired hemolytic disease in humans characterized by abnormal activation of complement on erythrocytes due to a deficiency of GPI-anchored complement regulatory proteins such as decay accelerating factor (N. Inoue, 2003). This disease is characterized by intravascular hemolysis and anemia. 

In the inflammatory muscle disease polymyocystitis autoantibodies are often directed against cytoplasmic proteins including aminoacyl-tRNA synthetases. In the rare paroxysmal cold hemoglobinuria autoantibodies attack red blood cell membranes only when the temperature of an extremity is lowered. Paroxysmal nocturnal hemoglobinuria, a serious complement-mediated condition, results from deficiency in the complement decay accelerating factor. This is a result of a defect in the PGI tail on this factor. ... 

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