Poly(ethylene glycol)s generate complement activation products in human serum through increased alternative pathway...

Area of Science:

• Immunology
• Biochemistry
• Polymer Science

Background:

• Poly(ethylene glycol) (PEG) is increasingly used intravenously for therapeutic purposes.
• PEG is generally considered immunologically safe, with limited understanding of its direct effects on the immune system.

Purpose of the Study:

• To investigate the immunogenic potential of Poly(ethylene glycol) (PEG) in human serum.
• To elucidate the mechanisms by which PEG activates the complement system.

Main Methods:

• Incubation of endotoxin-free PEG with human serum.
• Measurement of complement activation products (C4d, Bb, C3a-desArg, SC5b-9).
• Use of depleted sera (C2, C1q) and inhibitors (Futhan, anti-MASP-2, d-mannose, N-acetylglucosamine) to identify involved complement pathways.

Main Results:

• PEG rapidly generates complement activation products in human serum.
• Activation occurs via the lectin pathway (dependent on ficolins/MASP-2) and the alternative pathway.
• The extent of activation depends on PEG concentration and molecular weight.

Conclusions:

• Intravenous Poly(ethylene glycol) (PEG) can activate the human complement system.
• This activation poses a risk for acute infusion-related reactions in sensitive individuals and animals.
• PEG's immunogenicity may explain previously unexplained anaphylaxis and cardiovascular events associated with PEG-containing therapeutics.