Complement C4, Serum

Optimal Result: 12 - 38 mg/dL.

What is Complement component 4 (C4):

Complement component 4 (C4) is a blood test that measures the activity of a certain protein. This protein is part of the complement system.

What is the complement system?

The complement system 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, promotes inflammation, and attacks the pathogen’s cell membrane.

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.

There are nine major complement proteins. They are labeled C1 through C9.

C3 and C4 are the most commonly measured complement components. When the complement system is turned on during inflammation, levels of complement proteins may go down. Complement activity may be measured to determine how severe a disease is or if treatment is working.

What is a complement test being used for?

A complement test may be used to monitor people with an autoimmune disorder. For example, people with active systemic lupus erythematosusmay have lower-than-normal levels of the complement proteins C3 and C4.

Complement activity varies throughout the body. In people with rheumatoid arthritis, complement activity may be normal or higher-than-normal in the blood, but much lower-than-normal in the joint fluid.

More details on C4:

C4 is the most second-most abundant of the 11 complement proteins (after C3). It is also among the best studied. Levels of C4 are known to increase during inflammation and tissue destruction, and decrease during autoimmune disorders. The Complement C4 Blood Test helps determine the levels of C4 in blood. It is used to determine if deficiencies in the complement system are contributing to an immune disorder.

References:

Wang H, Liu M. Complement C4, Infections, and Autoimmune Diseases. Front Immunol. 2021 Jul 14;12:694928. doi: 10.3389/fimmu.2021.694928. PMID: 34335607; PMCID: PMC8317844.

Links:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698666/

https://www.ncbi.nlm.nih.gov/pubmed/26082779

https://www.ncbi.nlm.nih.gov/pubmed/26074922

What does it mean if your Complement C4, Serum result is too low?

Lower-than-normal complement C4 values could indicate:

- bacterial infections (especially Neisseria)

- hepatitis

- malnutrition

- rejection of a kidney transplant

- systemic lupus erythematosus, which is an autoimmune disease affecting the skin, joints, kidneys, and other organs

- lupus nephritis, which is a kidney disorder that often occurs as a result of systemic lupus erythematosus

- cirrhosis, which indicates significant liver damage

- glomerulonephritis, which is a type of kidney disease

- hereditary angioedema, which is a rare but serious autoimmune disease that causes swelling in various parts of the body

Complement component activity varies throughout the body. People with rheumatoid arthritis, for example, may have high complement levels in their blood but low complement levels in their joint fluid.

What does it mean if your Complement C4, Serum result is too high?

Complement C4, a key molecule in the complement system that is one of chief constituents of innate immunity for immediate recognition and elimination of invading microbes, plays an essential role for the functions of both classical (CP) and lectin (LP) complement pathways. Complement C4 is the most polymorphic protein in complement system.

Inflammatory conditions lead to an increase in C4 levels in the blood. The levels of C4 rise with low-grade inflammation. Inflammatory conditions that cause an increase in C4 levels include:

- Obesity, C4 levels increase with BMI
- Skin conditions such as psoriasis, dermatitis, and hives
- Ulcerative colitis and Crohn’s disease
- Psoriatic arthritis and rheumatoid arthritis
- Rheumatic fever
- Inflammation and kidney failure
- Certain types of cancers such as Hodgkin’s lymphoma, leukemia, and sarcoma
- Infection or injury

Levels of C4 are also seen to be elevated during pregnancy and due to use of certain drugs such as cimetidine.

Complement component activity varies throughout the body. People with rheumatoid arthritis, for example, may have high complement levels in their blood but low complement levels in their joint fluid.

Autoimmune diseases involve a lot of factors and may vary from one person to another. It is important to work with your healthcare provider to treat the underlying conditions that may cause your complement levels to be abnormal.

To prevent decrease in the levels of C4, it is advised to refrain from over eating and reducing intake of fatty foods. Supplements such as mangosteen are thought to boost up C4 levels. Avoiding cannabis, exposure to heavy metals and allergens is recommended to avoid C4 levels from going lower than normal.

Certain lifestyle and dietary changes can help reduce the risk of chronic inflammation and prevent the elevation in C4 levels. These changes may include losing weight, exercises, getting enough sleep, reducing stress, consuming an anti-inflammatory diet, etc.

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