Complement activation and disease: protective effects of hyperbilirubinaemia

Area of Science:

• Immunology
• Biochemistry

Background:

• The complement system is a crucial immune effector mechanism involving approximately 30 serum proteins.
• Complement can be activated via classical, alternative, or mannose-binding lectin pathways.
• Dysregulation of complement activation is linked to various diseases, making its pharmacological inhibition a therapeutic target.

Purpose of the Study:

• To detail the anti-complement properties of bilirubin.
• To explore the potential clinical relevance of bilirubin's interaction with the complement system.

Main Methods:

• Review of existing literature on complement activation and bilirubin's effects.
• Analysis of bilirubin's interference with C1q-immunoglobulin interactions.
• Proposal of a molecular model for UCB-C1q interaction.

Main Results:

• Bilirubin inhibits the classical complement pathway activation.
• Unconjugated bilirubin (UCB) interferes with the interaction between C1q and immunoglobulins.
• This inhibition occurs at bilirubin levels exceeding normal human serum concentrations.

Conclusions:

• Bilirubin exhibits anti-complement properties by blocking the initial step of classical pathway activation.
• The interaction between UCB and C1q is a key mechanism for this inhibition.
• Bilirubin's anti-complement activity holds potential clinical significance.