What conditions do you order Complement (C3-C4) labs for?

Complement C3-C4 Labs: Indications for Testing

Complement C3-C4 labs should primarily be ordered for patients with suspected or established systemic lupus erythematosus (SLE) to assess disease activity and monitor response to treatment. 1

Primary Indications for C3-C4 Testing

Systemic Lupus Erythematosus (SLE)

• Baseline assessment: All patients with suspected or newly diagnosed SLE should have C3 and C4 measured at baseline along with other autoantibodies (ANA, anti-dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, anti-phospholipid) 1
• Disease activity monitoring: Serial measurements of C3-C4 are valuable for assessing SLE activity and remission status 1, 2
• Lupus nephritis: Patients with established nephropathy should have C3, C4, and anti-dsDNA measured at least every 3 months for the first 2-3 years 1

Other Conditions Where C3-C4 Testing May Be Useful

• Complement deficiency disorders: Patients with recurrent infections or autoimmune manifestations may have inherited complement deficiencies 3
• Differential diagnosis: To help distinguish SLE from rheumatoid arthritis (RA), as complement levels typically decrease in active SLE but may be normal or elevated in RA 4

Pattern of Results and Clinical Significance

SLE-Specific Patterns

• Decreased C3 and C4: Strongly suggestive of active SLE, particularly with lupus nephritis 1, 5
• Correlation with disease activity: C3 levels generally correlate better with SLE disease activity than C4 levels 5
• C4d:C4 ratio: May be more sensitive than individual C3 or C4 measurements for monitoring immune complex formation and disease activity 6

Testing Algorithm

1. Initial Presentation:

   • Order C3-C4 as part of baseline workup for suspected SLE
   • Include other recommended autoantibodies: ANA, anti-dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, anti-phospholipid 1

2. Established SLE:

   • Monitor C3-C4 to assess disease activity/remission
   • Test more frequently (every 3 months) in patients with lupus nephritis 1
   • Consider alongside anti-dsDNA, which often changes inversely with complement levels

3. SLE Flare Assessment:

   • Decreasing C3-C4 levels may precede clinical flares
   • Terminal complement complex (TCC) measurements may offer better specificity (77% sensitivity, 80% specificity) than C3-C4 alone 5

Important Caveats and Pitfalls

• Normal levels don't exclude complement deficiency: Up to 50% of patients with partial C4A or C4B deficiencies may have normal C3, C4, and CH50 levels 3
• Complement consumption vs. deficiency: Low complement levels can reflect either consumption (active disease) or inherited deficiency
• Interpretation challenges: C3 and C4 are acute phase reactants and may be elevated due to inflammation, potentially masking consumption
• Limited specificity: Decreased complement levels can occur in other conditions with immune complex formation (not specific to SLE)
• Additional testing: For suspected complement deficiencies, more specialized testing like C4 protein allotyping may be necessary 3

Monitoring Frequency

• Active SLE: Every 3 months, especially with renal involvement 1
• Stable/Inactive SLE: Every 6-12 months 1
• After treatment changes: Consider more frequent monitoring to assess response

Remember that while C3-C4 levels are valuable biomarkers, they should be interpreted in the context of clinical findings and other laboratory parameters for optimal patient management.