What does a high complement c4 test mean?
General, Tests & Procedures

What Does It Mean To Have High Complement C4 Levels?

What Is The Role Of The Complement System?

The complement component 4 (C4) assay is a test used to detect the quantity of C4 complements present in human serum or plasma. It is produced in the liver and some white blood cells.

The complement system essentially contains a regulated network of proteins which has a significant role in inflammatory conditions and defense mechanisms of the host. The complement C4 test is therefore used for monitoring conditions such as inflammatory and auto-immune disorders.

The main job of the complement system in humans is to prevent the invasion of harmful microbes inside the body. Activation of the complement system results in opsonization (targeting) of pathogens and their destruction by the method of phagocytosis.

The function of the complement system is therefore not to just kill harmful pathogens but it also contains essential regulators and activators which provide us humoral and cellular immunity.

When Is A C4 Complement Test Advised?

A complement C4 test may be advised if your doctor suspects you of having an auto-immune disorder with signs and symptoms such as:

  • Frequent, persistent and recurrent infections
  • Butterfly-shaped rash across the cheeks
  • Hair loss
  • Ulcers in mouth or nose
  • Fatigue
  • Joint pain and swelling
  • Lightheadedness
  • Swelling around eyes (periorbital oedema) or over hands and feet

The complement C4 test may also be advised if you diagnosed with some kidney disease or a liver disorder such as hepatitis.

The test may also have to be repeated serially for the purpose of monitoring the progress of autoimmune disorders, liver or kidney disorders or to assess if the treatment is working beneficially.

Often, both C3 and C4 complement tests are usually advised together. This is because in certain diseases both complements C3 and C4 are low, while in some, one may be low and others are high or normal.

Some other tests may also be advised along with complement C4 test to assess the general immune status such as:

What Does A High Complement C4 Test Result Mean?

Normal Reference Range: 16 – 48 mg/dl
Complement C4 test result greater than the upper limit (more than 48 mg/dl) mentioned in the reference range is considered to be abnormal. Low complement C4 levels are often seen in autoimmune disorders or when there is an interference with C4 complement production such as liver diseases.
Low levels of C4 complement are associated with an increased risk of developing infections and autoimmune diseases.

C4 complement levels can rise in cases of trauma, injury or infections where there is the release of inflammatory mediators.

Conditions Caused By High Complement C4 Levels

Complement activity tends to vary throughout the body. Yet, significantly high complement C4 levels may be present along with other markers of inflammation (ESR, CRP, and homocysteine) in conditions such as


C4 complement levels are known to increase with the increase in body mass index (BMI) and can be higher among overweight and obese individuals

Crohn’s Disease And Ulcerative Colitis

Both of these are chronic inflammatory bowel diseases

Skin Disorders

Inflammatory conditions of the skin such as psoriasis, urticaria (hives) and dermatitis

Psoriatic Arthritis

A form of arthritis which develops as a long term complication in people already suffering from psoriasis

Rheumatoid Arthritis

Autoimmune disorder with primary affection of the joints characterized by joint pain, swelling, and redness of affected joints. Advanced and untreated cases of rheumatoid arthritis also show joint deformities.

Rheumatic Fever

Develops as a result of untreated strep throat which can also affect the heart, brain, skin, and joints as a course of the disease or its complication.

Various Types of cancers

Different types of cancers is also a reason for developing high complement C4 levels.

IgA Nephropathy

Also called Berger’s disease. Antibody deposition (immunoglobulin-A) within the kidneys produces an inflammatory reaction.


Complement C4 levels show a slight rise normally during pregnancy


Such as cimetidine can increase complement C4 levels

High levels of complement C4 in the blood can be deleterious for the overall functioning of the human body. High complement C4 levels can cause the following

Increases The Risk Of Developing Metabolic Syndrome

A study conducted over 3000 individuals supported the theory that high complement C4 levels were associated with a higher risk of developing metabolic syndrome.

Increases The Risk For Developing Heart Diseases

An observational study conducted included 5850 men, showed an association between high complement C4 levels and an increased risk of heart attack and stroke over a follow-up period of 18 months.

High complement C4 levels are also associated with other risk factors such as high cholesterol, blood pressure and body mass index (BMI).

Complement C4 test helps to determine if the presence of an immune disorder is due to its deficiency. If high complement C4 levels are not due to some major medical condition, the levels can be reduced effectively by following an appropriate diet and lifestyle which in return controls chronic inflammation. Some common measures include:

  • Weight loss measures if you have a high body mass index
  • Regular exercise
  • Getting enough refreshing sleep
  • Include Anti-Inflammatory Foods in Diet – Such as plenty of green leafy vegetables, tomatoes, nuts like almonds and walnuts, berries and citrus fruits.
  • Measures To Reduce Stress – Consult your doctor for the best ways suited to your particular needs

Complement C4 levels may vary even in different individuals having the same kind of illness. High complement C4 levels do not necessarily mean that you may have cancer or some major illnesses.

Yet, if complement C4 level is found to be raised, it cannot be considered as a ‘stand-alone” parameter to definitively a medical condition. Your doctor may advise you a different set of tests focusing on the probable diagnosis for high C4 levels and provide suitable treatment options for the underlying condition.

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