Paroxysmal nocturnal hemoglobinuria (PNH) results from a mutation in the blood-forming stem cells. PNH blood cells are more susceptible to destruction by a part of the immune system known as complement. This can result in severe anemia, 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, 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.
- Paroxysmal Nocturnal Hemoglobinuria (PNH)