Complement C4a
Other names: COMPLEMENT COMPONENT C4a, Plasma
Complement C4a or complement component 4a is a glycoprotein and peptide that is expressed, primarily in the liver and in macrophages, in response to acute inflammation or tissue injury. Complement C4a is part of the Complement C4 family.
The testing for C4a can help determine if a deficiency or abnormality is a contributing factor to increased infections or increased autoimmune activity. The measurement can also be used to monitor autoimmune disorders.
C4a, in conjunction with C3a, may be useful markers in acute and chronic Lyme disease.
Reference Ranges for Complement C4a:
→ Males: 152.0–1559.4 ng/mL
→ Females: 215.7–2025.9 ng/mL
References:
Nijs J, Van Oosterwijck J, Meeus M, Lambrecht L, Metzger K, Frémont M, Paul L. Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta. J Intern Med. 2010 Apr;267(4):418-35. doi: 10.1111/j.1365-2796.2009.02178.x. PMID: 20433584. https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2009.02178.x
Ingram G, Hakobyan S, Robertson NP, Morgan BP. Elevated plasma C4a levels in multiple sclerosis correlate with disease activity. J Neuroimmunol. 2010 Jun;223(1-2):124-7. doi: 10.1016/j.jneuroim.2010.03.014. Epub 2010 Apr 20. PMID: 20409594.
Links:
https://www.labcorp.com/tests/004330/complement-c-sub-4-sub-a
What does it mean if your Complement C4a result is too high?
Understanding Elevated Complement C4a Levels
Complement C4a is a protein fragment produced during the activation of the complement system, a crucial part of the immune response. Elevated levels of C4a are not specific to any single disease but generally indicate immune system activation and inflammation. Various conditions can lead to increased C4a levels:
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Normal Pregnancy: Pregnancy naturally activates the complement system. Increased levels of anaphylatoxins such as C3a, C4a, and C5a have been observed in the maternal bloodstream during healthy pregnancies.
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Antiphospholipid Syndrome (APS): Individuals with APS—an autoimmune disorder that leads to abnormal blood clotting—often have higher C3a and C4a levels compared to healthy individuals. APS can increase the risk of stroke, deep vein thrombosis, and pregnancy complications.
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Multiple Sclerosis (MS): Research by Ingram and colleagues found that C4a levels are elevated during MS relapses. MS is an autoimmune disease in which the immune system attacks the protective covering of nerves, disrupting communication between the brain and body.
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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A study by Nijs et al. (2010) found a strong relation between the change in complement C4a level and an increase in post-exertional pain and fatigue in ME/CFS patients.
Key Takeaway
While elevated C4a levels signal immune system activation, they are not diagnostic of a specific condition. These levels should be interpreted in the context of other clinical findings and laboratory results.
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