Reference distributions for complement proteins C3 and C4: a practical, simple and clinically relevant approach in a...

Area of Science:

• Immunology
• Biochemistry
• Clinical Chemistry

Background:

• Serum complement proteins C3 and C4 are key components of the complement cascade, acting as positive acute-phase proteins.
• Their response to cytokines is slower than other acute-phase proteins, taking days to elevate.
• Factors like infection, inflammation, hepatic failure, immune-complex formation, and genetic polymorphism influence C3 and C4 levels, complicating clinical interpretation.

Purpose of the Study:

• To examine reference ranges for serum C3 and C4 levels in a large cohort.
• To establish age- and gender-specific reference ranges for these complement proteins.
• To simplify the interpretation of C3 and C4 measurements in clinical practice.

Main Methods:

• Analysis of serum C3 and C4 levels from over 55,000 Caucasian individuals (1994-1999).
• Standardization of measurements against certified reference material (CRM 470/RPPHS).
• Exclusion of individuals with C-reactive protein ≥ 10 mg/L to avoid confounding inflammation.

Main Results:

• Serum C3 and C4 levels exhibit minimal change throughout life and between sexes, with slight increases and subsequent decreases noted in males and females at specific ages.
• Normalized C3 and C4 values, expressed as multiples of age- and gender-specific medians, followed a log-Gaussian distribution.
• The established distribution parameters allow for the assignment of centiles to individual measurements, facilitating interpretation.

Conclusions:

• Serum C3 and C4 levels are largely stable, with predictable age- and gender-related variations.
• A log-Gaussian distribution model provides a robust framework for interpreting C3 and C4 levels.
• Normalized centile reporting simplifies the clinical assessment of C3 and C4 measurements.