The Complement Total Hemolytic Assay (CH50 test) assesses the overall functional capacity of the immune system’s complement cascade. It evaluates how all components of the classical complement pathway work together. Clinicians use the CH50 result to screen for immune system dysfunction, including inherited deficiencies and conditions that cause excessive consumption of these protective proteins.
The Complement System: An Overview
The complement system is part of the innate immune response. It is a network composed of more than 50 proteins circulating in the blood, primarily synthesized by the liver. These proteins are inactive until they are triggered, initiating a sequential chain reaction known as a cascade.
The cascade results in three main defensive actions against foreign invaders and damaged cells:
- Opsonization, where complement proteins coat a pathogen, marking it for destruction by phagocytic immune cells.
- Generating fragments that promote localized inflammation and attract other immune cells to the site of infection or injury.
- Forming a structure that punches holes in the cell membranes of targeted bacteria, leading to cell lysis.
What the CH50 Test Measures
The CH50 test measures the functional activity of the classical activation pathway of the complement system. This pathway is activated when antibodies bind to an antigen, forming an immune complex that triggers the cascade. The test evaluates the combined activity of all nine major complement components, labeled C1 through C9.
The procedure uses a standardized laboratory method involving sheep red blood cells (SRBCs) pre-coated with anti-SRBC antibodies. The patient’s serum is mixed with these sensitized red cells, and the complement proteins attempt to lyse the SRBCs. The measurement reflects the serum dilution required to achieve 50% lysis of the red blood cells, recorded as the CH50 unit.
The assay requires careful handling of the blood sample to maintain protein activity. The sample must typically be fresh serum, separated quickly after collection and often frozen for transport, as complement proteins can rapidly degrade. The CH50 result provides a single value indicating the total hemolytic activity of the classical pathway, rather than the quantity of any individual protein.
Defining and Interpreting the CH50 Normal Range
The CH50 normal range represents the level of complement activity, though the exact numerical range varies between clinical laboratories. A commonly cited reference range is approximately 30 to 75 U/mL, but ranges of 90 to 150 U/mL or 100 to 300 U/mL are also used depending on the specific method employed. The patient’s lab report will always include the specific reference interval used for interpretation.
A result that falls below the established normal range is clinically significant. Low CH50 levels indicate that the complement system’s ability to lyse cells is impaired, which can be due to two primary reasons. First, a low result may signal consumption, meaning that the complement proteins are rapidly used up in an active disease process, such as when large amounts of immune complexes are cleared from the bloodstream. Second, a low or undetectable CH50 level can point to an inherited or acquired deficiency in one or more cascade components.
Conversely, an elevated CH50 result is less specific but still provides information to the clinician. High levels of total complement activity are often seen in acute inflammatory states. This elevation occurs because complement proteins act as acute phase reactants, meaning their production by the liver increases significantly in response to widespread inflammation or infection. While a high result may reflect generalized inflammation, the finding is considered alongside other blood markers and clinical symptoms for a complete assessment.
Clinical Applications of CH50 Testing
The CH50 test is an important screening tool used to help diagnose or monitor systemic autoimmune diseases, where immune complexes trigger constant activation and subsequent consumption of complement proteins. Systemic Lupus Erythematosus (SLE) is a prime example, where a decrease in CH50 levels often correlates directly with increased disease activity, serving as a marker for flare-ups.
The test is applied in the evaluation of kidney diseases involving immune complex deposition in filtering structures, such as glomerulonephritis. In these conditions, ongoing complement activation leads to depressed CH50 levels due to continuous consumption. CH50 testing is also used to identify individuals with hereditary complement deficiencies, which can cause increased susceptibility to recurrent or severe bacterial infections, especially those caused by encapsulated organisms.
Monitoring CH50 levels over time assesses a patient’s response to treatment for chronic conditions. For a patient with an autoimmune disorder, a successful therapeutic regimen should result in rising or normalizing CH50 values as disease activity decreases and protein consumption slows. Conversely, persistently low or decreasing levels suggest that the disease is progressing or that the current treatment plan is ineffective.