What are the indications for measuring total complement plasma levels?

Indications for Total Complement Plasma Level Measurement

Measure total complement levels (CH50 and/or AH50) when clinical presentation suggests complement deficiency, particularly in patients with recurrent neisserial infections, unexplained recurrent bacterial infections, or autoimmune manifestations resembling systemic lupus erythematosus. 1

Primary Clinical Indications

Suspected Complement Deficiency

• Recurrent neisserial infections (meningococcal or gonococcal meningitis) strongly suggest terminal complement component deficiency (C5-C9) 2
• Recurrent bacterial respiratory infections may indicate early classical pathway deficiencies including C1, C2, or C4 defects 2
• Lupus-like autoimmune disease in young patients warrants complement testing, as early complement component deficiencies (particularly C4) predispose to SLE-like syndromes 2

Evaluation When Other Immune Testing is Normal

• When antibody deficiency workup is normal but clinical presentation suggests immunodeficiency, consider complement deficiency or phagocyte defect 1
• The CH50 assay should be the initial screening test as it is readily available in most hospital laboratories 1

Disease-Specific Monitoring Indications

Systemic Lupus Erythematosus (SLE)

• Measure C3 and C4 at initial assessment and every 3 months in active SLE to monitor disease activity and treatment response 2
• Low C4 levels correlate with active disease, particularly lupus nephritis 2
• Serial measurements guide immunosuppressive therapy decisions 2
• Important caveat: C4 levels can decrease transiently post-vaccination in SLE patients without indicating disease flare 2

Complement-Mediated Glomerular Disease

• Comprehensive complement workup is indicated when kidney biopsy shows C4 deposition to distinguish C4 glomerulopathy from immune complex glomerulonephritis 2
• Immunofluorescence showing C4 without immunoglobulins indicates primary complement dysregulation requiring different therapeutic approaches 2

Algorithmic Approach to Complement Testing

Initial Screening

1. Start with CH50 (classical pathway) - most accessible and screens for C1, C2, C4, C3, and C5-C9 deficiencies 1
2. Add AH50 (alternative pathway) if CH50 is abnormal or clinical suspicion remains high 1

Interpretation Pattern

• CH50 = 0, AH50 normal: C1, C2, or C4 likely absent 1
• CH50 = 0, AH50 = 0: C3 or C5-C9 likely absent 1
• CH50 low, AH50 normal or low: Consumption likely, or regulatory component defect (factor H, factor I) 1
• CH50 normal, AH50 low: Properdin defect 1
• CH50 normal, AH50 = 0: Factor B or factor D defect (extremely rare) 1

Critical Technical Considerations

Sample Handling

• Blood specimens must be placed on ice or refrigerated immediately after drawing 1
• Complement components are unstable and degrade with warming 1
• This is a common pitfall leading to falsely low results

When to Suspect Complement Consumption

• If both factor B and C4 levels are low, assume complement consumption rather than deficiency 1
• Consumption patterns are seen in active SLE with systemic complement activation 3, 4
• In SLE, terminal complement complex (TCC) elevation can occur even when CH50 appears normal 5

Additional Context for Specific Scenarios

Hereditary Angioedema Consideration

• Low C4 with normal C3 in appropriate clinical context suggests hereditary angioedema 1
• These patients will have low (but not zero) CH50 results 1
• Proceed to C1 inhibitor level and function testing 1

Lectin Pathway Defects

• Both CH50 and AH50 will be normal in MBL (mannose-binding lectin) deficiency 1
• Requires specific MBL testing if clinically suspected 1