Inter-Individual Variations: A Challenge for the Standardisation of Complement Activation Assays

Area of Science:

• Immunotoxicology
• Nanomaterial Safety Assessment
• Complement System Biology

Background:

• Assessing chemical toxicity, including nanomaterials, requires understanding immune system responses, but complexity and interspecies variations pose challenges.
• Standardizing immunological tests is difficult due to individual variations in the human immune system.

Approach:

• Commercially available pooled sera (PS) and individual sera from healthy donors and patients (cancer, immunodeficiency, allergies) were treated with small molecules and liposomes.
• Complement activation was measured by quantifying iC3b protein levels using enzyme-linked immunosorbent assays.

Key Points:

• Complement activation levels in PS significantly differed from individual donor responses (p < 0.01).
• Sera from healthy donors showed high variability in response to PS; only 7/32 responded similarly.
• Responses to liposomes varied greatly in patients with allergies and immunodeficiency compared to PS, with allergy sufferers showing a 4.16-fold increase in iC3b.

Conclusions:

• Using pooled serum can lead to over- or under-estimation of immunological responses, particularly in individuals with pre-existing pathologies.
• Current practices of using pooled serum from healthy donors for predicting drug immunotoxicity need review, especially for nanomaterial-based products.
• Understanding individual toxicological responses to xenobiotics is crucial for robust safety assessments.