Paroxysmal nocturnal hemoglobinuria: role of the complement system, pathogenesis, and pathophysiology

The complement system complement system: A group of proteins that move freely in the bloodstream. These proteins support (complement) the work of white blood cells by fighting infections. is part of the innate immune response system, which comprises more than 50 distinct plasma plasma: The fluid part of the blood. Plasma is mostly made of water with chemicals in it. These chemicals include proteins, hormones, minerals, and vitamins. and serum proteins that interact to opsonize pathogens (i.e., mark pathogens for destruction) and induce inflammatory responses to fight infection. The role of the complement system is 2-fold: immune surveillance and host defense. Paroxysmal nocturnal hemoglobinuria Paroxysmal nocturnal hemoglobinuria: (par-uk-SIZ-muhl nok-TURN-uhl hee-muh-gloe-buh-NYOOR-ee-uh) A rare and serious blood disease that causes red blood cells to break apart. Paroxysmal means sudden and irregular. Nocturnal means at night. Hemoglobinuria means hemoglobin in the urine. Hemoglobin is the red part of red blood cells. A… (PNH) is a rare, chronic, acquired, hematologic disease caused by somatic mutations in the gene PIGA in the hematopoietic stem cells stem cells: Cells in the body that develop into other cells. There are two main sources of stem cells. Embryonic stem cells come from human embryos and are used in medical research. Adult stem cells in the body repair and maintain the organ or tissue in which they are found. Blood-forming (hemapoietic) stem… . These stem cells produce abnormal clone clone: To make copies. Bone marrow stem cells clone themselves all the time. The cloned stem cells eventually become mature blood cells that leave the bone marrow and enter the bloodstream. blood cells that lack the complement regulatory proteins CD55 and CD59, causing the body to recognize these otherwise healthy red blood cells as damaged. The complement system destroys cells without these protective proteins, resulting in general hemolysis hemolysis: (hi-MOL-uh-suss) The destruction of red blood cells. . PNH is characterized by fatigue; hemolytic anemia hemolytic anemia: Anemia due primarily to the excessive hemolysis or destruction of red blood cells that can be severe and debilitating; increased lactic dehydrogenase level, reticulocyte reticulocyte: An immature red blood cell. Reticulocytes are normally found in the bone marrow. They are present in the bloodstream only in very low numbers. count, and bilirubin bilirubin: (bil-i-ROO-bun) A reddish yellow substance formed when red blood cells break apart. It is found in the bile and in the blood. Yellowing of the skin and eyes can occur with high levels of bilirubin. Also called total bilirubin. level; propensity for thrombotic events; and renal dysfunction. Epidemiologic data, while sparse, suggest that an estimated 5,000-6,000 individuals in the United States are affected by PNH. If left untreated, PNH has a 10-year mortality rate of 29%, although the natural history of this disease has been recently altered by the introduction of complement inhibitors for the treatment of PNH. DISCLOSURES: This research was developed under a research contract between RTI Health Solutions and Apellis Pharmaceuticals and was funded by Apellis Pharmaceuticals. Bektas, Copley-Merriman, and Khan are employees of RTI Health Solutions. Sarda is an employee of Apellis Pharmaceuticals. Shammo consults for Apellis Pharmaceuticals.