C3 and C4 are used to determine whether deficiencies or abnormalities in the complement system are causing, or contributing to, a patient’s disease or condition. Total complement activity (CH50, or CH100) may be ordered to look at the integrity of the entire classical complement pathway. Other complement components are ordered as needed to look for deficiencies.

Complement testing may be ordered to help diagnose the cause of recurrent microbial infections, angioedema, or inflammation. It may be used to help diagnose and to monitor the activity of acute or chronic autoimmune diseases such as systemic lupus erythematosus (SLE). It may be tested and monitored with immune complex-related diseases and conditions such as: glomerulonephritis (a kidney disorder), serum sickness, rheumatoid arthritis, and vasculitis (inflammation of a blood vessel). When immune complexes form, complement helps to clear them from the blood, making levels of complement low.

Complement testing may be ordered when you have unexplained inflammation or edema, or symptoms of an autoimmune disorder such as SLE. It may also be ordered when your doctor suspects that you may have an immune complex-related condition and he wants to check the status of your complement system.

C3 and C4 levels are the most frequently ordered but others, such as C1 inhibitor, may be ordered when other deficiencies are suspected. Individual complement components may be ordered when the total complement activity (CH50, or CH100) is abnormal to help determine which of the components are deficient or abnormal.

When an acute or chronic condition has been diagnosed, complement testing may be used to help give a rough idea of the severity of the condition (with the assumption that the severity is linked to the decrease in complement levels). Complement testing may also be ordered occasionally when your doctor wants to monitor the current activity of your condition.

Complement levels may be decreased due to a hereditary deficiency (relatively rare) or due to increased consumption. Hereditary deficiency in one of the complement proteins will usually lead to a high frequency of recurrent microbial infections or autoimmune disease. If the deficiency is due to an underlying acute or chronic condition, complement levels will usually return to normal if the underlying condition can be resolved.

Decreased complement levels may be seen with:

• Recurrent microbial infections (usually bacterial)
• Autoimmune diseases, including SLE and vasculitis
• Hereditary angioedema
• Acquired angioedema
• Various types of kidney disease, including: glomerulonephritis, lupus nephritis, membranous nephritis, IgA nephropathy
• Malnutrition
• Septicemia
• Serum sickness (immune complex disease)

Complement protein levels are usually increased, along with other unrelated proteins called acute phase proteins, during acute or chronic inflammation. These all usually return to normal when the underlying condition is resolved. However complement proteins are rarely measured in these conditions, compared to the widely ordered C-reactive protein (CRP) and the relevance of their measurement in these situations is not reviewed here.

Increased and decreased complement levels will not tell your doctor what is wrong, but they will give him an indication that the immune system is involved with your condition. Complement levels can be increased with inflammation, rising before other markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).