Reference distributions for complement proteins C3 and C4: a comparison of a large cohort to the world's literature

Area of Science:

• Clinical Chemistry
• Immunology
• Biomarker Discovery

Background:

• Serum complement protein (C3 and C4) measurements are vital for diagnosis and prognosis.
• Current limitations in bedside use stem from a lack of credible reference materials and quantification methods.
• Technological advancements have improved measurement capabilities, but reliable reference intervals across all ages remain a challenge.

Purpose of the Study:

• To establish reliable, lifelong reference intervals for serum complement proteins C3 and C4 for both males and females.
• To address the remaining barrier to cost-effective and relevant clinical use of serum protein data.
• To provide a robust dataset supporting the use of established reference ranges in clinical practice.

Main Methods:

• A meta-analysis of 51 publications reporting reference intervals for C3 and C4.
• Statistical analysis of identified reference intervals meeting predefined criteria from prior studies.
• Comparison of newly analyzed lifelong reference ranges with findings from previous smaller studies.

Main Results:

• The meta-analysis statistically analyzed data from 51 publications.
• Established lifelong reference ranges were found to agree with previous smaller studies.
• The findings provide strong support for the proposed reference ranges.

Conclusions:

• The study provides validated, lifelong reference intervals for serum C3 and C4.
• These reference intervals are essential for accurate diagnosis and prognosis across all age groups.
• The findings facilitate more relevant and cost-effective clinical application of complement protein testing.