Complement C4

What Is Complement C4?

Complement C4 is a protein in the complement system—a cascade of plasma proteins that amplifies antibody and phagocyte action to clear pathogens. Upon activation, C4 promotes inflammation and recruits immune cells to sites of infection or tissue injury.

Normal and Optimal Ranges

• Standard Range (U.S.): 15.00–57.00 mg/dL
  
• Optimal Range: 16.00–34.00 mg/dL

   

Accurate interpretation often requires simultaneous measurement of C3 and C4, especially when evaluating for autoimmune disorders such as systemic lupus erythematosus.

Clinical Implications

Low Complement C4

• Systemic Lupus Erythematosus (SLE): Low C4 reflects immune complex consumption in active SLE and helps monitor disease flares and treatment response.
  
• Immune Deficiencies: Chronic low C4 may signal congenital or acquired complement deficiencies, predisposing to recurrent infections.

   

High Complement C4

• Cardiovascular Disease: Elevated C4 is linked to chronic inflammation and higher risk of cardiovascular dysfunction.
  
• Metabolic Syndrome: Increased C4 can accompany systemic inflammation in metabolic syndrome.

   

Interfering Factors & Drug Associations

• Increased by: Inflammation, estrogen therapy, oral contraceptives, pregnancy
  
• Decreased by: Corticosteroids, immunosuppressants, chemotherapy agents

   

Consider these when interpreting C4 to avoid misdiagnosis.

When to Test Complement C4

Complement C4 testing is indicated for:

• Evaluation of suspected autoimmune disease flares
  
• Assessment of chronic inflammatory conditions
  
• Cardiovascular risk stratification in patients with metabolic or inflammatory comorbidities

   

Conclusion

Complement C4 is an invaluable biomarker for gauging immune activity, inflammation, and disease risk. As a functional medicine nurse practitioner in Florida, I integrate C4 testing into a functional medicine framework—combining personalized nutrition, lifestyle interventions, and targeted therapies—to address root causes rather than just symptoms.

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Further Reading

• Zhou, W., & Yu, H. (2021). Complement C4, infections, and autoimmune diseases. Frontiers in Immunology, 12, 694928. https://pmc.ncbi.nlm.nih.gov/articles/PMC8317844/

• Osman, A. A., Ahmed, A. A., & Elhassan, A. M. (2023). Evaluation of serum complement C4 among COVID-19 patients in Khartoum State. PLoS ONE, 18(4), e0283766. https://pmc.ncbi.nlm.nih.gov/articles/PMC10390792/

• Yang, Y., Li, J., & Wang, Y. (2023). High plasma complement C4 levels as a novel predictor of clinical outcome after intracerebral hemorrhage. Frontiers in Aging Neuroscience, 15, 1103278. https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1103278/full

• Yang, Y., Chung, E. K., Zhou, B., Blanchong, C. A., Yu, C. Y., & Füst, G. (2004). Complete complement components C4A and C4B deficiencies in human kidney diseases and systemic lupus erythematosus. Journal of Immunology, 173(4), 2803-2814. https://journals.aai.org/jimmunol/article/173/4/2803/72596/Complete-Complement-Components-C4A-and-C4B