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Complement 4 (C4)
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C4 plays a crucial role in autoimmune surveillance, inflammation, and immune regulation
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Complement 4 (C4) Test Information Guide
- Why is it done?
- What the test measures: C4 is a protein component of the complement system, part of the immune system that helps destroy pathogens and regulate inflammation. This test measures the concentration of C4 protein in the blood.
- Primary indications for ordering: Evaluation of systemic lupus erythematosus (SLE) and other autoimmune conditions; investigation of recurrent infections; assessment of immune system dysfunction; monitoring of hereditary angioedema; evaluation of glomerulonephritis and other complement-mediated diseases.
- Typical timing and circumstances: Performed during initial evaluation of suspected autoimmune disease; ordered when patients present with symptoms suggestive of SLE such as joint pain, rash, or kidney involvement; used during follow-up to assess disease activity and treatment response; obtained when investigating complement deficiency or recurrent bacterial infections.
- Normal Range
- Reference values: 15-45 mg/dL (or 0.15-0.45 g/L); Normal range may vary slightly between laboratories based on testing methodology and population studied.
- Units of measurement: Milligrams per deciliter (mg/dL) or grams per liter (g/L).
- Result interpretation: Results are typically reported as numerical values. Values within the reference range (15-45 mg/dL) are considered normal. Values below the lower limit indicate low C4 levels (hypocomplementemia). Values above the upper limit are less common but may indicate certain inflammatory states. Results should always be interpreted in clinical context.
- What normal vs abnormal means: Normal C4 levels generally indicate adequate complement protein production and utilization. Low C4 levels (below 15 mg/dL) suggest increased consumption or utilization of complement, often due to immune activation from autoimmune disease, infection, or complement deficiency. Significantly elevated levels are rare but may indicate acute phase response or certain inflammatory conditions.
- Interpretation
- Low C4 levels (below 15 mg/dL): Often indicates active autoimmune disease, particularly systemic lupus erythematosus (SLE); associated with immune complex-mediated diseases; may suggest active lupus nephritis or vasculitis; can indicate C4 deficiency or complement activation due to infection; frequently correlated with disease activity in SLE patients.
- Normal C4 levels (15-45 mg/dL): Generally indicates normal immune function; argues against active systemic lupus erythematosus; suggests adequate complement production; does not completely exclude autoimmune disease but makes active disease less likely.
- Elevated C4 levels (above 45 mg/dL): Uncommon result; may indicate acute inflammatory response; can occur during acute phase of infection; may suggest acute hepatitis or other inflammatory states; less clinically significant than low levels.
- Factors affecting results: Active infection can consume complement proteins; liver disease may impair complement synthesis; certain medications can influence immune function; sample handling and timing affect reliability; hemolysis or improper storage may yield inaccurate results; C4 levels fluctuate with disease activity in chronic conditions.
- Clinical significance of patterns: Persistently low C4 with positive ANA suggests active SLE; low C4 with clinical symptoms of lupus activity (flare) has high clinical significance; normal C4 during clinical symptoms may point to other diagnoses; serial C4 measurements showing decline indicate worsening disease; rising C4 levels during treatment suggest therapeutic response.
- Associated Organs
- Primary organ systems involved: Immune system (primary); liver (produces complement proteins); kidneys (affected by complement-mediated disease); blood vessels; skin.
- Medical conditions associated with abnormal results: Systemic lupus erythematosus (SLE); lupus nephritis; immune complex-mediated glomerulonephritis; rheumatoid arthritis; Sjögren's syndrome; post-streptococcal glomerulonephritis; membranoproliferative glomerulonephritis; hepatitis B and C; C4 deficiency; hereditary angioedema; severe infections; cryoglobulinemia.
- Diseases helped diagnosed or monitored: SLE diagnosis and activity monitoring; autoimmune kidney disease; complement deficiency disorders; immune complex diseases; recurrent infection evaluation; vasculitis assessment.
- Potential complications with abnormal results: Low C4 may indicate ongoing immune-mediated organ damage (kidney disease, vasculitis); increased risk of infection with congenital C4 deficiency; lupus nephritis can progress to end-stage renal disease; untreated autoimmune disease can cause multi-organ involvement; severe infections possible with complement deficiency; cardiovascular complications from vasculitis.
- Follow-up Tests
- Additional tests if abnormal results: Complement 3 (C3) level; C1q level; total complement activity (CH50); Antinuclear antibody (ANA); anti-dsDNA and anti-Smith antibodies; urinalysis; serum creatinine; blood urea nitrogen (BUN); liver function tests; complete blood count.
- Complementary investigations: Kidney biopsy if lupus nephritis suspected; chest imaging if pulmonary involvement present; imaging studies to assess organ damage; genetic testing if hereditary complement deficiency suspected.
- Monitoring frequency: For SLE patients: C4 typically monitored every 3-6 months; more frequently during disease exacerbation or after treatment changes; baseline and periodic assessment in new diagnoses; serial measurements more informative than single values.
- Related complementary tests: C3 protein; C1q; CH50 (total hemolytic complement); immunoglobulin levels; rheumatoid factor; anticardiolipin antibodies; lupus anticoagulant; C-reactive protein; erythrocyte sedimentation rate.
- Fasting Required?
- Fasting requirement: No - Fasting is not required for C4 testing. This test can be performed on a non-fasting blood sample.
- Special instructions: No specific dietary restrictions needed; patient may eat and drink normally before the test; routine hydration is acceptable and may be beneficial for blood draw.
- Medications and preparation: No medications need to be avoided before this test; continue taking all regular medications as prescribed; immunosuppressive medications, corticosteroids, and antimalarials commonly used in SLE treatment do not interfere with C4 testing.
- Other preparation requirements: Arrive for blood draw in comfortable, relaxed state; wear loose-fitting clothing to facilitate easy blood draw; inform phlebotomist of any previous difficult venipunctures; sample collection should be in tubes specified by laboratory; samples should be processed and refrigerated promptly for best accuracy.
How our test process works!
