Overview of Laboratory Testing and Clinical Presentations of Complement Deficiencies and Dysregulation

Area of Science:

• Immunology
• Clinical Chemistry

Background:

• Complement disorders were historically associated with immunodeficiency and infection.
• Recent research highlights complement's role in inflammation, autoimmune diseases, and vision loss, shifting diagnostic paradigms.
• The development of complement inhibitors necessitates a deeper understanding for effective patient management.

Purpose of the Study:

• To provide an overview of complement pathways.
• To summarize recent literature on complement dysregulation in various diseases.
• To discuss analytical methods and challenges in clinical complement testing.

Main Methods:

• Literature review of complement pathways and associated disorders.
• Summary of recent findings in hereditary angioedema, autoimmune diseases, and age-related macular degeneration.
• Discussion of complement's role in atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria, and C3 glomerulopathies.

Main Results:

• Complement's role extends beyond immunodeficiency to inflammation and autoimmune conditions.
• Dysregulation of complement is implicated in diverse diseases including angioedema, AMD, and specific kidney and blood disorders.
• Analytical methods for complement testing face challenges in clinical laboratories.

Conclusions:

• A paradigm shift in understanding complement disorders requires updated diagnostic and interpretive approaches.
• Accurate complement testing is essential for diagnosis, monitoring, and guiding therapy with emerging complement inhibitors.
• Further research and improved analytical methods are needed to address the complexities of complement system assessment.