Serum complement is a group of globulin proteins that act as enzymes. These enzymes facilitate the immunologic and inflammatory response. The complement system is important for destroying foreign cells and isolating “foreign” antigens. The total complement, sometimes labeled CH50, is made up of nine major components, C1 through C9. Besides these major components, there are some subcomponents and “inhibitor” components involved in the system. Classic complement activation starts when an immunoglobulin (Ig) M or IgG antibody binds with the C1 q subcomponent of C1. C1 activates C4, which activates C2 and so on to C9. There are also alternative pathways for the activation of this system.
When complement is activated, it also increases very important processes that occur during a normal inflammatory response. These processes are:
- Chemotaxis: The process in which White Blood Cells are attracted to the designated area.
- Phagocytosis: The process in which foreign microorganisms are contained by and lysed a White Blood Cell.
- Immune Adherence: The process on which antibodies a Red Blood Cell engage with invading microorganisms.
Complement Assay test mainly used to diagnose Angioedema. The test is also used to monitor the activity of Nephritis, Membranoproliferative Nephritis, Poststreptococcal Nephritis, or Systemic Lupus Erythematosus (SLE).
Total complement can be measured by hemolytic tests. For this test, the patient’s blood is mixed with antibody-coated red blood cells (RBCs) of sheep. The end point is when 50% of the RBCs are lysed. The patient’s blood is serially diluted and results are reported in complement units per milliliter. Specimens for complement assays may be sent out to reference laboratories. These tests assess the overall function of the entire complement system. The C3 and C4 components can be quantitated by direct immunologic measurement. These subcomponents are measured when total complement has been found to be reduced. C3 makes up the majority of the component of complement. It is made in the liver and to a lesser degree in the spleen, skin, and other lymphoid nodules. C4 is made in the bone and lung.
Reduced complement levels can be congenital, as in hereditary angioedema. Hereditary angioedema is a congenital lack of a C1 “inhibitor” (often called C1 esterase). The complement system is overly activated and the complement components are “consumed” or used up. Serum levels fall.
Acquired complement deficiency occurs with diseases that are associated with increased antibody/antigen complexes. Here again, these complexes serve to act as complement activators. If the presence of these complexes is chronic, the complement system is overly activated and the complement components are consumed or used up. Serum levels fall. Diseases associated with immune complexes such as those described include serum sickness, lupus erythematosus, infectious endocarditis, renal transplant rejection, vasculitis, and some forms of glomerulonephritis. When these diseases are successfully treated, complement levels can be expected to return to normal.
Complement components are increased following the onset of various acute or chronic inflammatory diseases or acute tissue damage. This is very similar to an acute-phase reactant protein.
- C3 is very unstable at room temperature. If the specimen is left standing for more than 1 hour, complement levels could be falsely low. The serum should be separated out and frozen immediately when the specimen is received.
Normal Complement Levels
Total complement: 75-160 units/mL or 75-160 kunits/L (SI units)
C3: 55-120 mg/dL or 0.55-1.20 g/L (SI units)
C4: 20-50 mg/dL or 0.20-0.50 g/L (SI units)
Causes of High Complement levels
- Acute Rheumatic Fever.
- Acute Myocardial Infarction (AMI).
- Ulcerative colitis.
- Inflammatory illnesses, stress, and trauma: Complement can develop very similarly to an acute-phase reactant protein. With these illnesses, complement is increased.
- Cancer: The pathophysiology of this observation is unknown.
Causes of Low Complement Levels
- Hereditary angioedema: Hereditary angioedema is a congenital lack of a C1 “inhibitor” (often called C1 esterase). The complement system is overly activated and the complement components are consumed or used up. Serum levels fall.
- Severe liver diseases such as hepatitis or cirrhosis: The liver is the site of synthesis of many of the complement components. Synthesis is decreased in the presence of liver disease. Serum levels fall.
- Autoimmune disease (SLE, glomerulonephritis, lupus nephritis, rheumatoid arthritis [severe and active], Sjögren syndrome).
- Serum sickness (immune complex disease).
- Renal transplant rejection (acute): These diseases are associated with the increased presence of antibody/antigen complexes, which serve to act as complement activators. The complement system is overly activated and complement components are consumed. Serum levels fall. Protein malnutrition.
- Malnutrition: These diseases are associated with protein depletion. Complement is a protein and its synthesis can be expected to be reduced in these illnesses.
- Infection such as gram-negative sepsis or bacterial endocarditis.
- Glomerulonephritis (specifically poststreptococcal and membranoproliferative): Alternate pathways of complement activation occur. The complement system is overly activated and complement components are consumed. Serum levels fall.