Glycosylphosphatidylinositol or glycophosphatidylinositol (GPI) is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in a wide variety of biological processes. GPI is composed of a phosphatidylinositol group linked through a carbohydrate-containing linker and via an ethanolamine phosphate (EtNP) bridge to the C-terminal amino acid of a mature protein. The two fatty acids within the hydrophobic phosphatidyl-inositol group anchor the protein to the cell membrane.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. Other key features of the disease, such as the high incidence of venous blood clot formation, are incompletely understood.
Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene.
Phosphatidylinositol-glycan-specific phospholipase D is an enzyme that in humans is encoded by the GPLD1 gene.
GPI transamidase component PIG-T is an enzyme that in humans is encoded by the PIGT gene.
GPI-anchor transamidase is an enzyme that in humans is encoded by the PIGK gene.
Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q is an enzyme that in humans is encoded by the PIGQ gene.
Phosphatidylinositol N-acetylglucosaminyltransferase subunit C is an enzyme that in humans is encoded by the PIGC gene.
Phosphatidylinositol-glycan biosynthesis class F protein is a protein that in humans is encoded by the PIGF gene.
GPI transamidase component PIG-S is an enzyme that in humans is encoded by the PIGS gene. This gene encodes a protein that is involved in GPI-anchor biosynthesis.
Phosphatidylinositol glycan anchor biosynthesis class U protein is a protein that in humans is encoded by the PIGU gene.
GPI mannosyltransferase 3 is an enzyme that in humans is encoded by the PIGB gene.
Subunit P of phosphatidylinositol N-acetylglucosaminyltransferase is an enzyme subunit that in humans is encoded by the PIGP gene.
Phosphatidylinositol N-acetylglucosaminyltransferase subunit H is an enzyme that in humans is encoded by the PIGH gene. The PIGH gene is located on the reverse strand of chromosome 14 in humans, and is neighbored by TMEM229B.
Fluorescein-labeled proaerolysin (FLAER) is used in a flow cytometric assay to diagnose paroxysmal nocturnal hemoglobinuria (PNH). The assay takes advantage of the action of proaerolysin, a prototoxin of aerolysin, a virulence factor of the bacterium Aeromonas hydrophila. Proaerolysin binds to the glycophosphatidylinositol(GPI) anchor in the plasma membrane of cells. Cells affected by PNH lack GPI anchoring proteins, and thus are not bound by proaerolysin. Of note, the FLAER-based assay is not suitable for evaluation of erythrocytes and platelets in PNH but flow cytometry assays based on CD55, CD59 and others are suitable.
Glypiation is the addition by covalent bonding of a glycosylphosphatidylinositol (GPI) anchor and is a common post-translational modification that localizes proteins to cell membranes. This special kind of glycosylation is widely detected on surface glycoproteins in eukaryotes and some Archaea.
Phosphatidylinositol glycan anchor biosynthesis, class N is a protein that in humans is encoded by the PIGN gene.
Ravulizumab, sold under the brand name Ultomiris, is a humanized monoclonal antibody complement inhibitor medication designed for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome. It is designed to bind to and prevent the activation of Complement component 5 (C5).
Pig-a gene mutation assay is a flow cytometry-based method for detecting mammalian cells that have inactivating mutations in the endogenous X-linked reporter gene called phosphatidyl inositolglycan class A gene. PIG-A is involved in the synthesis of glycosylphosphatidylinositol (GPI), an anchor molecule that tethers multiple protein marker molecules at the surface of the cells. When the sample containing wild-type and PIG-A mutant cells is labeled with fluorescent antibodies raised against GPI-anchored protein markers the wild-type cells will fluoresce and PIG-A mutant cells will not. The fraction of non-fluorescent PIG-A mutant cells in the antibody-labeled sample can be efficiently determined on any of the modern high throughput flow cytometers. The PIG-A mutant frequency fraction can be determined with high accuracy within minutes by processing samples containing a total of a million cells or more.
The sucrose lysis test is a diagnostic laboratory test used for diagnosing paroxysmal nocturnal hemoglobinuria (PNH), as well as for hypoplastic anemias and any hemolytic anemia with an unclear cause. The test works by using sucrose, which creates a low ionic strength environment that allows complement to bind to red blood cells. In individuals with PNH, some red blood cells are especially vulnerable to lysis caused by complement. The test may also produce suspicious results in other hematologic conditions, including megaloblastic anemia and autoimmune hemolytic anemia. False-negative results can occur when complement activity is absent in the serum. A simpler alternative called the sugar water test also involves mixing blood with sugar and observing for hemolysis, using the same principle as the sucrose lysis test.
