When C1 esterase inhibitor levels are elevated, do you perform a C1q test?

When to Perform C1q Testing in Elevated C1 Esterase Inhibitor Levels

When C1 esterase inhibitor (C1-INH) levels are elevated, you should not perform a C1q test, as C1q testing is primarily indicated when C1-INH levels are decreased to differentiate between hereditary angioedema (HAE) and acquired C1-INH deficiency. 1

Diagnostic Algorithm for Angioedema

The diagnostic approach to angioedema follows a specific pattern based on complement levels:

1. Initial screening: C4 level is the recommended first-line test for suspected angioedema

   • Low C4 suggests possible C1-INH deficiency
   • Normal C4 during an attack makes HAE unlikely 1

2. Secondary testing: If C4 is low, measure C1-INH antigen and function

   • Type I HAE: Low C1-INH antigen + low function
   • Type II HAE: Normal C1-INH antigen + low function 1

3. C1q testing role: Only indicated to differentiate between:

   • HAE: Normal C1q levels
   • Acquired C1-INH deficiency: Decreased C1q levels 1, 2

When to Order C1q Testing

C1q testing is specifically indicated in the following scenarios:

• When C1-INH levels and C4 levels are both decreased 1
• In patients over 40 years with new-onset angioedema and low C1-INH 2
• When suspecting acquired C1-INH deficiency associated with lymphoproliferative disorders 3, 4
• To differentiate between hereditary and acquired forms of C1-INH deficiency 1

Important Clinical Considerations

• C1q testing has no diagnostic value when C1-INH levels are elevated
• Elevated C1-INH is not typically associated with either HAE or acquired angioedema
• When ordering C1q, specifically request "C1q level" and not "C1q binding" (which tests for immune complexes) 1
• C1q levels should be normal in patients with HAE but decreased in most cases of acquired C1-INH deficiency 1

Common Pitfalls to Avoid

• Don't confuse C1q binding assay with C1q level measurement
• Pregnancy can affect C1-INH levels, requiring cautious interpretation and confirmation postpartum 1
• C1-INH functional assays may be more reliable than antigenic measurements alone 1
• False-positive and false-negative results can occur, especially in young children, so repeat testing may be necessary 1

In summary, C1q testing is a valuable diagnostic tool but only when C1-INH levels are decreased, not elevated. The test helps distinguish between hereditary and acquired forms of C1-INH deficiency, with the latter typically showing decreased C1q levels.