Complement C3 and Complement C4

Complement C3 and Complement C4

Synonym/acronym: C3 and C4.

Common use

To assist in the diagnosis of immunological diseases, such as rheumatoid arthritis, and systemic lupus erythematosus (SLE), in which complement is consumed at an increased rate, or to detect inborn deficiency.


Serum (1 mL) collected in a red- or red/gray-top tube. Place separated serum into a standard transport tube within 2 hr of collection.

Normal findings

(Method: Immunoturbidimetric) C3
AgeConventional UnitsSI Units (Conventional Units × 10)
Newborn57–116 mg/dL570–1,160 mg/L
6 mo–adult74–166 mg/dL740–1,660 mg/L
Adult83–177 mg/dL830–1,770 mg/L
AgeConventional UnitsSI Units (Conventional Units × 10)
Newborn10–31 mg/dL100–310 mg/L
6 mo–6 yr15–52 mg/dL150–520 mg/L
7–12 yr19–40 mg/dL190–400 mg/L
13–15 yr19–57 mg/dL190–570 mg/L
16–18 yr19–42 mg/dL190–420 mg/L
Adult12–36 mg/dL120–360 mg/L


Complement is a system of 25 to 30 distinct cell membrane and plasma proteins, numbered C1 through C9. Once activated, the proteins interact with each other in a specific sequence called the complement cascade. The classical pathway is triggered by antigen-antibody complexes and includes participation of all complement proteins C1 through C9. The alternate pathway occurs when C3, C5, and C9 are activated without participation of C1, C2, and C4 or the presence of antigen-antibody complexes. Complement proteins act as enzymes that aid in the immunological and inflammatory response. The complement system is an important mechanism for the destruction and removal of foreign materials. Serum complement levels are used to detect autoimmune diseases. C3 and C4 are the most frequently assayed complement proteins, along with total complement.

Circulating C3 is synthesized in the liver and comprises 70% of the complement system, but cells in other tissues can also produce C3. C3 is an essential activating protein in the classic and alternate complement cascades. It is decreased in patients with immunological diseases, in whom it is consumed at an increased rate. C4 is produced primarily in the liver but can also be produced by monocytes, fibroblasts, and macrophages. C4 participates in the classic complement pathway.

This procedure is contraindicated for



  • Detect genetic deficiencies
  • Evaluate immunological diseases

Potential diagnosis

Normal C4 and decreased C3Acute glomerulonephritis, membranous glomerulonephritis, immune complex diseases, SLE, C3 deficiency
Decreased C4 and normal C3Immune complex diseases, cryoglobulinemia, C4 deficiency, hereditary angioedema
Decreased C4 and decreased C3Immune complex diseases

Increased in

  • Response to sudden increased demand

  • C3 and C4
    • Acute-phase reactions
  • C3
    • Amyloidosis
    • Cancer
    • Diabetes
    • Myocardial infarction
    • Pneumococcal pneumonia
    • Pregnancy
    • Rheumatic disease
    • Thyroiditis
    • Viral hepatitis
  • C4
    • Certain malignancies

Decreased in

    Related to overconsumption during immune response

    C3 and C4
    • Hereditary deficiency (insufficient production)
    • Liver disease (insufficient production related to damaged liver cells)
    • SLE
    • Chronic infection (bacterial, parasitic, viral)
    • Post–membranoproliferative glomerulonephritis
    • Post–streptococcal infection
    • Rheumatic arthritis
    • Angioedema (hereditary and acquired)
    • Autoimmune hemolytic anemia
    • Autoimmune thyroiditis
    • Cryoglobulinemia
    • Glomerulonephritis
    • Juvenile dermatomyositis
    • Meningitis (bacterial, viral)
    • Pneumonia
    • Streptococcal or staphylococcal sepsis

Critical findings


Interfering factors

  • Drugs that may increase C3 levels include cimetidine and cyclophosphamide.
  • Drugs that may decrease C3 levels include danazol and phenytoin.
  • Drugs that may increase C4 levels include cimetidine, cyclophosphamide, and danazol.
  • Drugs that may decrease C4 levels include dextran and penicillamine.

Nursing Implications and Procedure


  • Positively identify the patient using at least two unique identifiers before providing care, treatment, or services.
  • Patient Teaching: Inform the patient this test can assist in diagnosing diseases of the immune system.
  • Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex.
  • Obtain a history of the patient’s immune system and results of previously performed laboratory tests and diagnostic and surgical procedures.
  • Obtain a list of the patient’s current medications, including herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus).
  • Review the procedure with the patient. Inform the patient that specimen collection takes approximately 5 to 10 min. Address concerns about pain and explain that there may be some discomfort during the venipuncture.
  • Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
  • Note that there are no food, fluid, or medication restrictions unless by medical direction.


  • Potential complications: N/A
  • Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
  • Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
  • Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection. Perform a venipuncture.
  • Remove the needle and apply direct pressure with dry gauze to stop bleeding. Observe/assess venipuncture site for bleeding or hematoma formation and secure gauze with adhesive bandage.
  • Promptly transport the specimen to the laboratory for processing and analysis.


  • Inform the patient that a report of the results will be made available to the requesting health-care provider (HCP), who will discuss the results with the patient.
  • Reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP. Answer any questions or address any concerns voiced by the patient or family.
  • Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy. Evaluate test results in relation to the patient’s symptoms and other tests performed.

Related Monographs

  • Related tests include anticardiolipin antibody, ANA, complement total, cryoglobulin, and ESR.
  • Refer to the Immune System table at the end of the book for related tests by body system.
Handbook of Laboratory and Diagnostic Tests, © 2013 Farlex and Partners
References in periodicals archive ?
Complement C3 and complement C4 in SLE patients with and without infection
We analyzed the serum complement C3 and complement C4 levels in 97 SLE patients with infection and in 59 SLE patients without infection and found that the levels of complement C3 in SLE patients with infection were similar to those in patients without infection (mean rank, 77.82 vs 79.61, U=2796.0, P=0.811; Figure 3A).
Two additional SLE diagnostic biomarkers of disease activity are the serum complement C3 and complement C4 levels.
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