Halting targeted and collateral damage to red blood cells by the complement system.

Area of Science:

• Immunology
• Hematology
• Pharmacology

Background:

• The complement system is crucial for pathogen defense but can cause self-damage in diseases like PNH and AIHA.
• Red blood cells (RBCs) in PNH lack regulators, while antibodies trigger complement in AIHA, leading to hemolysis.
• Eculizumab is a standard treatment for PNH, but limitations exist regarding efficacy, cost, and side effects.

Purpose of the Study:

• To review the pathophysiology of complement-mediated hemolysis in PNH and AIHA.
• To discuss the current role and limitations of therapeutic complement inhibition.
• To highlight emerging complement inhibitors targeting specific pathways or improving administration.

Main Methods:

• Literature review of complement system pathophysiology in PNH and AIHA.
• Analysis of current therapeutic complement inhibitors and their clinical impact.
• Survey of novel complement inhibitors under investigation.

Main Results:

• Complement system dysregulation drives RBC destruction in PNH and AIHA.
• Existing complement inhibitors show efficacy but have drawbacks including cost and infection risk.
• Numerous novel complement inhibitors are in development, targeting various complement proteins and pathways.

Conclusions:

• Complement-mediated hemolysis is a key feature of PNH and AIHA.
• Therapeutic complement inhibition has advanced treatment, but unmet needs persist.
• Ongoing research focuses on targeted, cost-effective, and patient-friendly complement inhibitors.