Atypical C-ANCA following high dose intravenous immunoglobulin

Area of Science:

• Immunology
• Clinical Diagnostics
• Medical Laboratory Science

Background:

• Antineutrophil cytoplasmic antibody (ANCA) testing is crucial for diagnosing certain autoimmune conditions.
• Intravenous immunoglobulin (IVIG) products are widely used for various immune deficiencies and autoimmune diseases.
• Atypical C-ANCA patterns can complicate diagnostic interpretation.

Purpose of the Study:

• To evaluate IVIG products for atypical C-ANCA staining.
• To determine if high-dose or replacement-dose IVIG therapy causes atypical C-ANCA patterns in patients.
• To assess if clinical laboratories can distinguish atypical C-ANCA from classical ANCA using external quality assessment.

Main Methods:

• Indirect immunofluorescence and ELISA were used to test 30 IVIG batches.
• ANCA testing was performed on patients receiving high-dose (2 g/kg/month) or replacement (200 mg/kg fortnightly) IVIG.
• A positive IVIG batch was blindly tested by 125 laboratories via the UK National External Quality Assessment Scheme (NEQAS).

Main Results:

• 16 of 31 IVIG batches showed atypical C-ANCA positivity.
• Three of six patients on high-dose IVIG tested positive for atypical C-ANCA; none on replacement doses did.
• NEQAS results showed 68% of laboratories incorrectly identified the atypical pattern as classical C-ANCA.

Conclusions:

• Certain IVIG products can induce atypical C-ANCA staining via indirect immunofluorescence.
• High-dose IVIG, not replacement doses, may lead to this observed atypical pattern in patients.
• The high rate of misclassification in NEQAS underscores the importance of reporting only "classical ANCA" to maintain diagnostic specificity.