Challenges for complement functional assays in the clinical laboratory: From test validation to clinical...

Area of Science:

• Clinical immunology
• Laboratory medicine
• Complement system biology

Background:

• Complement functional assays are vital for diagnosing diverse disorders, including immune deficiencies, autoimmune diseases, and thrombotic microangiopathies.
• These assays assess complement pathways and components, aiding in diagnosis and disease monitoring.
• The increasing use of complement inhibitors necessitates reliable laboratory assessment of treatment efficacy.

Purpose of the Study:

• To discuss the challenges and limitations of current complement functional assays.
• To highlight the need for standardization and improved practices in clinical laboratories.
• To address the demand for personalized treatment plans through accurate complement assessment.

Main Methods:

• Review of current complement functional assay methodologies.
• Discussion of pre-analytical and analytical challenges.
• Analysis of regulatory status and validation requirements for laboratory-developed tests (LDTs).

Main Results:

• Complement proteins are labile, requiring strict handling protocols (prompt processing, cold centrifugation, -80°C storage).
• Only one FDA-approved complement functional test exists; others are LDTs requiring rigorous validation.
• Harmonization across laboratories is hindered by varying methodologies and calibrators.

Conclusions:

• Complement functional assays are essential but technically demanding.
• Standardization and improved laboratory practices are critical for reliable complement testing.
• Further development and validation of assays are needed to support personalized medicine and complement inhibitor therapy.