Clinical significance of C3 and C4 . complement testing

The article was written by MSc Tran Quynh Trang, Laboratory Department - Vinmec Times City International General Hospital

Complement includes more than 20 different serum proteins, which contribute to the body's defenses by many different pathways. C3 and C4 are two major components of the complement system, helping to evaluate the function of the complement system and its role in immune response, infections, and autoimmune diseases.

Complement is used to refer to a component in the serum that is not heat stable, can lyse bacteria, and contributes to the body's defense by different ways.
Complement can opsonize bacteria to enhance phagocytosis, localization and activation of various cells including polymorphonuclear leukocytes and macrophages, involved in the regulation of responses of antibodies, which aid in the clearance of immune complexes and apoptotic cells.
Complement includes more than 20 different serum proteins produced by a wide range of cells including: hepatocytes, macrophages and intestinal epithelial cells.

Some complement proteins bind to immunoglobulins or other components of cell membranes. Many other components are in the form of pro-enzymes, which, when activated, cleave one or more other complement proteins. After cleaving some of the complement proteins, fragments have the ability to activate cells, increase vascular permeability or opsonize bacteria.
Complement activation can be divided into four pathways: the classical pathway, the lectin pathway, the edge pathway, and the membrane attack pathway. Regardless of which pathway is activated, the final product produced will be a protein complex capable of destroying the cell membrane of the antigen.
To evaluate the function of the complement system as well as its role in immune responses, infections, or autoimmune diseases, two major components of the complement system are often quantified: C3, C4.
Although genetic deficiency of C3 is extremely rare, deficiencies in other more common components (although still very rare) can lead to low C3 rates. A genetic deficiency in C4 is rarely detected.

Quantification of C3, C4 helps:
Detect the causes leading to disorders of kidney tissue, joints, connective tissue, glomerulonephritis, vasculitis. Causes of immunodeficiency associated with recurrent infections. Normal C4 concentration: 20-50 mg/dl.
C4 levels are increased in: cancer, rheumatoid arthritis, rheumatoid arthritis (rheumatoid spondylitis).
Low C4 levels indicate immune complex disease. They are found most commonly in cases of active systemic lupus erythematosus (SLE), rheumatoid vasculitis (but not uncomplicated rheumatoid arthritis where C4 levels are usually normal), chronic active hepatitis, congenital C4 deficiency, hereditary angioedema.
Normal concentration C3: 90-180mg/dl. Values ​​up to twice this upper limit were found in the acute phase.
Blood C3 levels increase in: acute rheumatism, rheumatoid arthritis, cancer.
Blood C3 levels decrease in: SLE, glomerulonephritis, sepsis. Low C3 levels associated with low C4 levels suggest an activated classical pathway. They are found most commonly in active SLE cases. Low C3 levels associated with normal levels of C4 demonstrate alternative pathway activation suggestive of infectious disease or renal factor activity.
Although in some patients with long-term SLE C3 levels remain low, this does not necessarily indicate active disease, a sudden drop often indicates exacerbation of the disease and risk of kidney damage .
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