Total complement activity (TCA) refers to a series of tests that determine the functioning of the

complement system The complement system, also known as complement cascade, 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 at ...

in an individual.

Tests

A variety of tests can be used to measure TCA, but the most commonly used on is the CH50 test. Other tests include the liposome immunoassay (LIA), single tube titration method, and the plate-hemolysis method.

CH50 Procedure

The test is based on the capacity of an individual's serum to lyse sheep erythrocytes coated with anti-sheep antibodies (preferably rabbit

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...

). The individual's serum is diluted until the minimum concentration is reached that 50% of the sheep red blood cells are lysed, and that concentration is recorded as the CH50. The CH50 is testing the

classical complement pathway The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and IgM ...

in an individual thus requiring functioning C1-C9 factors.

CH50 Interpretation

If an individual has deficient or malfunctioning complement factors, then at a baseline they have decreased capacity to lyse the erythrocytes. Therefore, any dilution to their serum would further impair this functioning, meaning that a lower dilution needs to be reached to achieve 50% capacity. In contrast, any individual with increased complement levels or activity would have an elevated CH50 since increasing dilution would be necessary to reach the 50% lyse marking. Decreased CH50 values may be seen in

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...

hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...

as a result of impaired complement production in the liver. It can also be seen in

systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

as a result of increased usage of complement factors due to the pathology of the autoimmune condition. It is decreased during attacks of

hereditary angioedema Hereditary angioedema (HAE) is a disorder that results in recurrent attacks of severe swelling. The swelling most commonly affects the arms, legs, face, intestinal tract, and airway. If the intestinal tract is affected, abdominal pain and vomitin ...

(but those with the disease have a normal value in between attacks). Increased CH50 values means that their complement is hyperfunctional relative to normal, and this may be seen in

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and a ...

. One can interpret the CH50 value along with the individual's complement factor values to help determine the etiology. For example, if and individual has normal C3/C4 values but a decreased CH50, that can indicate a

terminal complement pathway deficiency Terminal complement pathway deficiency is a genetic condition affecting the complement membrane attack complex (MAC). It involves deficiencies of C5, C6, C7, and C8. (While C9 is part of the MAC, and deficiencies have been identified, it is ...

while if one has low C3 and CH50 values that can indicate an autoimmune condition such as

. Alternative pathway hemolytic assay ("AH50") can be used in conjunction to indicate if there is a terminal pathway deficiency (CH50 and AH50 both are low), classical pathway deficiency (CH50 low, AH50 normal) or alternative pathway deficiency (AH50 low, CH50 normal).

References

Complement system Immunologic tests {{med-diagnostic-stub