Selective IgM digestion improves anti-AAV IgG detection in the immune complex assay format
Uwe Wessels1, Alexander Pöhler1, Francesca Ros1
1Roche Pharma Research & Early Development (pRED), Pharmaceutical Sciences, Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany.
Bioanalysis
|September 3, 2025
Summary
Anti-adenovirus-associated virus (AAV) IgM antibodies interfere with IgG detection in immune complex (IC) assays. Selective IgM digestion enhances the accuracy of anti-AAV IgG measurements in these assays.
Area of Science:
- Immunology
- Virology
Background:
- Adeno-associated virus (AAV) is a common viral vector used in gene therapy.
- Assays detecting anti-AAV antibodies are crucial for patient stratification and monitoring treatment efficacy.
- Interference from other antibody isotypes, such as IgM, can affect the accuracy of IgG detection assays.
Purpose of the Study:
- To confirm IgM interference in anti-AAV IgG immune complex (IC) assays.
- To evaluate the efficacy of IgM-specific digestion in improving anti-AAV IgG detection.
Main Methods:
- Anti-AAV2 and anti-AAV9 IgG signals were measured using IC assays.
- Assays were performed both with and without IgM-specific digestion.
- Anti-AAV2 and anti-AAV9 IgM signals were measured concurrently.
Main Results:
- IgM digestion significantly increased anti-AAV2 and anti-AAV9 IgG signals when corresponding IgM antibodies were present.
- This indicates that co-existing anti-AAV IgM antibodies interfere with IgG detection in IC assays.
Conclusions:
- Anti-AAV IgM antibodies interfere with the anti-AAV IgG immune complex assay.
- Selective IgM digestion is an effective method to improve the detection of anti-AAV IgG in IC assays.
