A group of essential membrane proteins that are absent in all hematopoietic cells in PNH are known as complement-regulatory surface proteins, and these proteins play a key role in the regulation of the complement system. These include decay acceleration factor (DAF) or CD55, homology restriction factor (HRF) or C8-binding protein, and membrane-reactive cleavage inhibitor (MIRL) or CD59.
These complement regulatory surface proteins regulate the process of complement activation by interacting with complement proteins, particularly C3b and C4B. They are capable of dissociating invertase complexes of classical and alternative pathways, thereby controlling the activation and amplification of the complement system. In patients with PNH, due to genetic mutations or other reasons, the expression of these complement-regulated surface proteins is absent or dysfunctional, resulting in uncontrolled activity of the complement system, attacking blood cells such as normal red blood cells, and triggering symptoms such as hemolysis.
*Strategies for PNH primarily include control of hemolysis and prevention of complications, as well as exploration of targets for the complement system. Several complement inhibitors have been approved for **PNH, which reduce hemolysis and associated symptoms by inhibiting the activity of the complement system. However, these drugs do not alter the underlying defects of the disease and therefore need to be sustained**.
Allogeneic hematopoietic stem cell transplantation is a potential method, but requires the identification of a histologically compatible donor and is associated with significant morbidity and mortality. Therefore, this ** method is usually reserved for severe cases, such as cases of PNH with aplastic anemia or transformation into leukemia.
More research is needed to better understand the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH) and to develop more effective methods. Deepening the mechanism of action of complement regulatory surface proteins in hematologic malignancies will help provide patients with better options.