Complement 4 (C4) Test

complement c4 test

Last Updated December 20th, 2021

What is the Complement 4 test?

The complement system consists of more than 30 specific proteins that circulate in the blood and tissue fluids. It is a functional part of the immune system and forms an important defence mechanism against the invasion of various pathogens. These proteins work along with the antibodies and phagocytic cells to clear pathogens and damaged cells from the body. The system can get activated in response to the components of microorganisms that invade the body.

Among the three different pathways that can get the complement system activated, the C4 protein is an integral component of multiple ones. The C4 test measures the level of the protein in the bloodstream. Apart from C4, there are nine other major complement proteins which are designated by the numbers 1 to 9 affixed with the C.

The complements form the membrane attack complex which destroys the cell surface of a microbe, thereby killing it.  They help in attracting neutrophils and macrophages to the specific sites and also perform anti-inflammatory functions. Since these proteins can be harmful to the host cells, their cascading action is controlled by other plasma and cell membrane proteins, along with sialic acid present in the cell membranes.

Any deficiency in the control mechanisms can result in over-production of complements, leading to conditions like inflammation and cell lysis. In many cases, the levels of C3 and C4 are measured together for a better diagnosis of certain problems.

The lower levels of C4 can be related with the risk of infections or the development of an autoimmune disorder. The higher levels can be associated with chronic inflammations or a disease like cancer or ulcerative colitis

A certain percentage of the population can have genetic traits that can lead to a deficiency of C4 in the blood, leading to a congenital C4 deficiency. The complement activity varies through the body and in some cases, while the levels in the blood can be higher than normal, the levels in a joint fluid can be lower than normal. 

In many cases, C4 levels are measured to check for diseases like lupus and rheumatoid arthritis. The test is also used to check the severity of a particular disease and to monitor the effectiveness of the treatment at times. Since this test is not a specific indicator of any particular disease, the doctor might order follow up tests for a specific diagnosis.

Why do I need to undergo a Complement 4 test?

The doctor may order the test in case the development of any autoimmune disease is suspected and that may involve the following symptoms.

– Extreme fatigue
– Muscle pain or weakness
– Joint pain
– Any sudden, unexpected weight loss

The test is also used often along with the C3 test to specifically check for lupus. The symptoms of lupus include the following.

Rash in the shape of a butterfly across the cheeks
– Mouth or nose ulcers
– Hair loss
– Joint pain and inflammation
– Swelling around the eyes and also in the hands and feet
– Difficulty in breathing or pain during deep breathing

The test is also done for patients who are suspected of being affected with autoimmune hemolytic anemia, chronic hepatitis or rheumatoid arthritis. The test is also used for the diagnosis of various infections like pneumonia, meningitis or gonorrhoea.

The exact C4 levels enable the doctors to judge the overall effectiveness of any ongoing treatment for an autoimmune condition. In some children, the test is used to diagnose a few specific conditions mentioned below.

-Henoch-Schonlein purpura, a condition involving the inflammation of the blood vessel

– Childhood diabetes mellitus

How is a Complement 4 test performed?

The procedure for the test is simple and the entire method can be completed within a few minutes. The process involves the collection of the required volume of blood from a vein, which is usually selected from the elbow region or from the back of the hand. The process involves the following steps.

– The site is first disinfected with an antiseptic.

– The health care provider wraps an elastic band around the upper arm in order to apply some pressure to the area and make the vein swell with blood. This makes the process of collection easier.

– The needle is generally inserted into the vein. This step will result in a slight stinging sensation or pain for some patients.

-The blood is withdrawn and it gets collected into an airtight vial or tube attached to the needle. After the required volume is collected, the band is removed from the arm.

-The needle is then removed, the collection site is covered by a cotton ball and a slight pressure is applied on it to stop any bleeding.

In the case of infants or young children, veins are difficult to find and in many cases, a sharp tool called a lancet is used to break the skin and collect the required volume of blood. In some adult patients, veins may not be distinctly visible, making the collection process difficult. In such cases, multiple punctures can be needed.

The collection site might develop bruises or a throbbing sensation may be felt after the collection. While most patients do not show any side effects, for a few, symptoms like the ones mentioned below can occur- .

– Excessive bleeding
– A sensation of dizziness or light-headedness
– Fainting
– An infection at the puncture site
– These conditions will need special medical attention at the earliest.

What is the price for a Complement 4 test in India?

The cost of the test varies between Rs 600 to Rs 2000 depending on the location and facilities provided in the testing centre.

When will I get the test results?

In general, the test results are generally delivered within 24 to 72 hours, depending on the laboratory.

What is the normal range for a Complement 4 test?

The normal range of C4 in the blood is 15 to 45 milligrams per deciliter (mg/dL). The range of normal values can vary slightly between laboratories. Since the test results depend on a variety of factors, you should always consult your doctor for the correct interpretation of the levels.

What do the results mean?

When the levels of C4 are increased, it can be an indication of any of the following conditions.

– Cancer
Ulcerative colitis

The decreased levels can be indicative of the following conditions.

Bacterial infections
– Cirrhosis that indicates liver damage
– Glomerulonephritis, which is a type of kidney disease.
– Hereditary angioedema, an autoimmune disease that causes swelling
– Kidney transplant rejection
-Lupus nephritis
– Systemic lupus erythematosus
In case C4 levels are undetectable whereas the C3 levels are normal, it can be indicative of a congenital C4 deficiency. The doctor can order further tests to confirm a specific diagnosis and before planning for the treatment.

Do I need to fast for the Complement 4 test?

No fasting or any other special preparation is needed before the C4 test.

What else do I need to know before I appear for a Complement 4 test?

The test can be used for the interpretation of a wide variety of conditions and the following points will provide a better insight into some other aspects about it.

It is necessary to inform the doctor about any medications, vitamins, herbs and other supplements that you might be consuming before appearing for the test. This also includes any over-the-counter medicines or illegal drugs as they might affect the test results.

In many cases, the doctor can use the test results to check for the effectiveness of any treatment and if your C4 values are moving up, it indicates that the treatment is yielding positive results.

As mentioned earlier, the test does not indicate any specific condition and is a general indicator that something is wrong with the immune system. For this reason, further blood tests can be ordered for a more specific diagnosis.

Can pregnant women undergo a Complement 4 test?

Pregnant women can undergo the test without any restrictions.

Is Complement 4 test possible for new-born babies?

The test is possible for new-born babies in line with the recommendations from the doctor.


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