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What is a Complement 4 (C4) test? 

Compliment 4 or C4 is one of the 20 proteins of the complement system - an important component of the body’s immune system. They are present in an inactive form in the blood and body fluids and are only activated after the entry of an infectious agent or antigen (a foreign substance). The main function of the complement system is to activate white blood cells (WBCs) to kill invading bacteria and viruses and prevent infection. It also promotes the removal of dead cells from the body. However, disorders in the complement system may cause the immune system to attack the healthy cells of the body, resulting in inflammation and autoimmune diseases.

A C4 test measures the level of C4 proteins in the blood. It is commonly done along with a C3 test to determine detect the cause of repeated infections and diagnose autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and rheumatic fever.

  1. Why is a C4 test performed?
  2. How do you prepare for a C4 test?
  3. How is a C4 test performed?
  4. C4 test results and normal range

A C4 test is a blood test which is done to assess the functioning of the complement system. The levels of C3 and C4 are altered in various conditions such as cancer, rheumatoid arthritis and SLE, depending on the process and nature of the disease. C4 test helps evaluate the severity of the disease and is also used to assess the effectiveness of treatment. Doctors order a C4 test if you have the following symptoms:

  • Stiffness in joints, especially on waking in the morning
  • Pain and swelling in joints
  • Small joints of hands and feet such as wrist, ankle, fingers and toes are more painful than the large joints such as knee and hip joints
  • Ulcers inside the mouth or nose
  • Dryness in the body - oral dryness, reduced vaginal fluids and decreased production of tears
  • Hair loss
  • Red rash on the skin, especially on the face, nose and cheek (butterfly rash)
  • Pale fingers that become numb when exposed to cold
  • Fever
  • Weight loss
  • Extreme weakness and tiredness

Some other tests may be ordered along with C4 and C3 tests include total complement activity test (CH50), erythrocyte sedimentation rate (ESR), tests to measure specific antibodies and tests to detect the involvement of kidneys, heart, liver and muscles. These tests are used to confirm the diagnosis of suspected diseases such as rheumatoid arthritis and SLE.

You do not have to do any special preparation before a C4 test. Fasting is not essential before this test. Please inform your doctor if you are taking any prescription or non-prescription medicines or supplements.

A laboratory technician will withdraw a blood sample from a vein in your arm and collect it in a red-top test tube for the test. The test is performed under strict hygienic and aseptic conditions. Reports are usually obtained in one day.

Few mild side effects of this test include infection, bleeding and haematoma (bleeding under the skin) at the site of needle insertion. People with a weak immune system may also notice fever, dizziness and weakness after the test.

Normal results: 

The reference range for C4 is 15-45 mg/dL (milligrams per decilitre) or 0.15-0.45 g/L (grams per litre).

Normal results indicate absence of infections, autoimmune disorders or deficiency of C4 in the body. They are indicative of a properly functioning complement system.

Abnormal results:

Increased levels of C4 suggest the presence of the following conditions:

  • Infection
  • Metastatic cancer
  • Necrotising disorders such as necrotising fasciitis. Necrotising fasciitis is an autoimmune disorder which is associated with the death of infected tissue or fascia (thin sheet of connective tissue between the skin and muscles). Symptoms of this condition include high fever with extreme pain, redness and swelling in the infected area. The affected area of skin develops black, blue, red and purple spots, with fluid-filled boils between these spots
  • Rheumatoid arthritis
  • Rheumatic fever 
  • Ulcerative colitis. It is an autoimmune disease of the large intestine, with symptoms such as a sudden urge to pass stools, loss of appetite, nausea, anaemia, fever, weight loss and extreme tiredness.

Decreased levels of C4 are seen in the following conditions:

  • Congenital C4 deficiency (Deficiency of C4 from birth)
  • Chronic liver disorders such as liver cirrhosis and hepatitis (inflammation in the liver)
  • Kidney disorders such as acute glomerulonephritis, rejection of kidney transplant and uraemia
  • SLE
  • Disorders related to bleeding and clotting such as disseminated intravascular coagulopathy (DIC), Henoch-Schonlein purpura and cryoglobulinaemia
  • Vasculitis (inflammation in the walls of blood vessels)
  • Heart disorders such as subacute bacterial endocarditis
  • Disorders of the immune system such as multiple sclerosis and serum sickness
  • Hereditary angioneurotic oedema

Disclaimer: All results must be clinically correlated with the patient’s complaints to make a complete and accurate diagnosis. The above information is provided from a purely educational point of view and is in no way a substitute for medical advice by a qualified doctor.

References

  1. Holers VM. Complement and its receptors: new insights into human disease. Annu Rev Immunol. 2014;32:433-59. PMID: 24499275.
  2. Arthur C. Guyton, M.D., John E. Hall, Ph.D. Textbook of Medical Physiology. Resistance of the Body to Infections: II. Immunity and Allergy. 11th edition. 1956. Pp: 445
  3. Denise D. Wilson. McGraw-Hill’s Manual of Laboratory & Diagnostic Tests. Complement Assay (C3 and C4 Complement). 2008. Pp.175, 176.
  4. Johns Hopkins Medicine [Internet]. The Johns Hopkins University, The Johns Hopkins Hospital, and Johns Hopkins Health System; Rheumatoid Arthritis Signs and Symptoms
  5. University of Rochester Medical Center [Internet]. Rochester (NY): University of Rochester Medical Center; Complement C4 (Blood)
  6. Tietz, NW, Textbook of Clinical Chemistry. 3rd edition.1999. Siemens Dimensions Vista C4 Flex Insert. March, 2011
  7. National Organisation of Rare Disorders [Internet]. Danbury, CT, U.S. Necrotizing Fasciitis
  8. National Institute of Diabetes and Digestive and Kidney Diseases [internet]: US Department of Health and Human Services; Ulcerative Colitis
  9. Ward M, Eastwood MA.. Serum C3 and C4 complement components in ulcerative colitis and Crohn's disease. Digestion. 1975;13(1-2):100-3. PMID: 1201816.
  10. Frances T Fischbach RN, BSN, MSN. A Manual of Laboratory and Diagnostic Tests. Total Hemolytic Complement (CH50). C4 Complement Component. 7th edition. July 2003. Pp. 374

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