Complement was discovered by Jules Bordet as a heat-labile component of normal plasma that causes the opsonisation and killing of bacteria. The complement system refers to a series of >20 proteins, circulating in the blood and tissue fluids. Most of the proteins are normally inactive, but in response to the recognition of molecular components of microorganisms they become sequentially activated in an enzyme cascade – the activation of one protein enzymatically cleaves and activates the next protein in the cascade.
The complement system plays a critical role in inflammation and defence against some bacterial infections. Complement may also be activated during reactions against incompatible blood transfusions, and during the damaging immune responses that accompany autoimmune disease. Deficiencies of individual complement components or inhibitors of the system can lead to a variety of diseases, which gives some indication of their role in protection against disease.
The Complement Total, or CH50 Blood Test, assesses the overall activity of the complement system, and mainly evaluates the classic complement activation pathway. A CH50 Blood Test is often ordered to evaluate complement component deficiency and evaluate complement activity in cases of immune complex disease, glomerulonephritis (inflammation of the kidneys filters), rheumatoid arthritis and cryoglobulinemia (abnormal proteins in the blood that thicken in cold temperatures). It can also be used to evaluate a persons response to systemic lupus erythematosus (SLE) therapy and predict disease flares.
This test is usually ordered for people with a family history of complement deficiency and those who have symptoms of:
- RA
- kidney disease
- lupus, which is a multisystem autoimmune disease
- myasthenia gravis
- an infectious disease, such as meningitis
- cryoglobulinemia, which is the presence of abnormal proteins in the blood
What does it mean if your Complement, Total (CH50), Quest Diagnostics result is too high?
What Does an Elevated Complement, Total (CH50) Level Mean?
Complement, Total (CH50) is a blood test that measures the overall activity of the classical complement pathway—a crucial part of your immune system. This pathway helps defend against infections, clear damaged cells, and trigger inflammation.
What Is CH50 and How Is It Measured?
The CH50 test determines how much your serum (the liquid part of your blood) is needed to lyse, or break apart, 50% of antibody-coated red blood cells in a laboratory setting. Typical reference ranges for CH50 are usually between 30–75 U/mL or 41–90 hemolytic units, though these values may vary by laboratory.
What Does an Elevated CH50 Level Indicate?
An elevated CH50 level means the complement system is more active than normal. This is less common than a low CH50 and is generally a nonspecific marker—meaning it doesn’t point to one single disease, but instead signals increased immune activity or inflammation.
What Can Cause Elevated CH50 Levels?
-
Acute Inflammation or Infection
During infections or acute inflammation, the liver may increase production of complement proteins (like C3 and C4), resulting in higher CH50 levels. -
Autoimmune Diseases in Early or Active Phases
Some autoimmune conditions—such as rheumatoid arthritis or systemic lupus erythematosus (SLE)—may show temporarily increased complement activity during early or flare stages. However, as these diseases progress, complement levels often drop due to consumption. -
Chronic Inflammatory Conditions
Diseases such as sarcoidosis, vasculitis, or inflammatory bowel disease (IBD) may show elevated complement activity because of ongoing immune system activation. -
Certain Cancers or Lymphoproliferative Disorders
Some cancers, especially those involving the immune or lymphatic systems, can lead to increased complement production due to immune dysregulation. -
Recovery After Complement Consumption
After a period of low complement levels (for example, during active autoimmune disease), CH50 may rebound and become elevated during recovery or following successful treatment as inflammation resolves.
How Is CH50 Used Clinically?
CH50 is primarily used to:
-
Evaluate the function of the classical complement pathway
-
Monitor disease activity in autoimmune conditions
-
Investigate recurrent infections or suspected complement deficiencies
-
Assess response to immunosuppressive therapy
It’s important to note that low CH50 is more commonly used for diagnosis (especially in lupus or complement deficiency), while elevated CH50 is a less specific finding.
Other Tests That May Be Ordered With CH50
-
C3 and C4 complement levels
-
ANA and other autoantibodies (for autoimmune workup)
-
CRP and ESR (markers of inflammation)
-
Infectious disease testing
-
Immunoglobulin levels
Summary
An elevated Complement, Total (CH50) level typically reflects increased immune system activity, most often due to infection, inflammation, an autoimmune flare, or occasionally certain cancers. It is a nonspecific finding and should always be interpreted alongside your symptoms, medical history, and other laboratory markers. Most clinical concern centers on low CH50, but a high value can provide useful context in understanding your immune system’s current state.
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What does it mean if your Complement, Total (CH50), Quest Diagnostics result is too low?
Levels of complement may be depressed in genetic deficiency, liver disease, chronic glomerulonephritis, rheumatoid arthritis, hemolytic anemias, graft rejection, systemic lupus erythematosis, acute glomerulonephritis, subacute bacterial endocarditis and cryoglobulinemia.
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