Complement tests measure the activity or concentration of complement proteins in the blood. Complement is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen’s cell membrane. There are several types of complement tests, each with different utilities:
- Total Complement Activity (CH50):
- Screening for Complement System Activity: This test measures the overall activity of the classical complement pathway. It is a good screening test for total complement activity, and a low result may suggest a deficiency in one or more complement components.
- Identifying Consumption: Low levels may also be found when complement is being used up (consumed) by ongoing immune complex diseases, such as systemic lupus erythematosus (SLE).
- C3 and C4 Component Tests:
- Disease Activity in Specific Conditions: These tests measure the levels of the two most important complement proteins in the blood. Low levels of C3 and C4 may indicate active autoimmune disease, such as SLE, particularly during a flare-up.
- Complement Consumption or Deficiency: These tests are often ordered together, and decreased levels of both can indicate consumption due to ongoing inflammation or an inherited deficiency.
- Alternative Pathway Activity (AH50):
- Detecting Alternative Pathway Issues: Similar to CH50, this test evaluates the integrity of the alternative complement pathway. It is often used when CH50 is low but no deficiency is found in the classical pathway components.
- Complement Factor I, Factor H, and Factor B:
- Diagnosing Atypical Hemolytic Uremic Syndrome (aHUS): These tests can be useful in diagnosing conditions such as atypical hemolytic uremic syndrome, where abnormal regulation of complement leads to blood cell damage.
- C1 Esterase Inhibitor (C1-INH) Level and Function Tests:
- Diagnosing Hereditary Angioedema: Used to diagnose and monitor hereditary angioedema, a condition characterized by episodes of severe swelling. Both quantitative and functional assays are important to evaluate the proper function of C1-INH.
- Complement Autoantibodies:
- Autoimmune Complement Disorders: For example, anti-C1q antibodies are associated with lupus nephritis, and their presence can sometimes correlate with disease severity.
- C2 Tests:
- Diagnosis of C2 Deficiency: Individuals with a C2 deficiency often have recurrent bacterial infections, particularly of the respiratory tract.
- Assessment of Immune Complex Diseases: Low C2 levels may also be found in conditions associated with immune complexes, such as SLE, where there is activation and consumption of complement
- Investigating Hereditary Angioedema: Although less common, some forms of hereditary angioedema are associated with complement deficiencies, including C2.
Clinical Utility of Complement Tests:
- Diagnosis of Complement Deficiencies: Inherited or acquired deficiencies in complement proteins can lead to recurrent infections or autoimmune disease.
- Monitoring Disease Activity and Flares: Complement levels, especially C3 and C4, are often used in conjunction with other tests to monitor disease activity in conditions such as SLE
- Investigating Recurrent Bacterial Infections: Complement deficiencies might be suspected in individuals with recurrent infections, especially those caused by encapsulated bacteria.
- Assessment of Kidney Disease: Complement levels are sometimes assessed in kidney diseases such as post-infectious glomerulonephritis and membranoproliferative glomerulonephritis.
- Evaluating Unexplained Inflammation or Angioedema: Low complement levels may help explain symptoms of unexplained inflammation or episodes of angioedema.
Abnormal complement levels can be a sign of a problem with the innate immune system, but they must be interpreted in the context of the patient’s clinical presentation and other laboratory findings, as they are not specific to a single disease.