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) results from a mutation mutation: Any change or alteration in a gene. A mutation may cause disease or may be a normal variation. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a mutation in the PIG-A gene of a single stem cell in the bone marrow. in the blood-forming 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… . PNH blood cells are more susceptible to destruction by a part of the immune system known as complement. This can result in severe anemia anemia: (uh-NEE-mee-uh) A condition in which there is a shortage of red blood cells in the bloodstream. This causes a low red blood cell count. Symptoms of anemia are fatigue and tiredness. , blood clotting, and many other symptoms that interfere with quality of life and can even be life threatening. Recently, there has been an expansion of different therapies to treat PNH. In addition to their various modes of administration (e.g., oral, intravenous, injection), these therapies target different proteins in the complement pathway. There is no available test to measure therapeutic levels of all these drugs and assess whether complement is fully blocked. This proposal will validate a test, called the bioluminescent modified Ham, that can monitor the effect of all available anti-complement therapeutics. Secondly, there are no ways to predict who may respond best to specific therapies. We will explore whether low levels of CR1, a protein on red blood cells that regulates 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. , can predict who needs certain anti-complement therapeutics. We will also evaluate why CR1 is reduced in PNH as compared to the general population. In summary, our proposal will establish tests to predict and monitor response to PNH therapies. These tests can be rapidly applied to the treatment of patients.