Resolving falsely elevated vancomycin levels in KIMS immunoassay due to monoclonal IgM interference

Area of Science:

• Clinical Chemistry
• Immunology
• Laboratory Medicine

Background:

• Accurate vancomycin concentration monitoring is crucial due to its narrow therapeutic index and nephrotoxicity risk.
• Immunoassays like Kinetic Interaction of Microparticles in Solution (KIMS) are susceptible to interference from paraproteins, including monoclonal immunoglobulins.
• Monoclonal immunoglobulins can cause falsely elevated drug concentrations, complicating patient management.

Purpose of the Study:

• To report the first case of falsely elevated vancomycin concentrations due to monoclonal IgM interference using KIMS.
• To evaluate pre-analytical methods for mitigating this specific interference.
• To assess the efficacy of dithiothreitol (DTT), ultrafiltration, and heterophilic blocking tubes (HBT) in resolving the interference.

Main Methods:

• A case of falsely elevated vancomycin levels detected by KIMS with a 'kinetic flag' error was investigated.
• Pre-analytical treatments included dithiothreitol (DTT) to reduce IgM disulfide bonds, ultrafiltration (100-kDa cutoff) to remove IgM, and HBT to block heterophilic antibodies.
• Vancomycin concentrations were measured using KIMS and Chemiluminescent Microparticle Immunoassay (CMIA) post-treatment.

Main Results:

• Both DTT treatment and ultrafiltration resolved the 'kinetic flag' error and corrected vancomycin concentrations to below the lower limit of quantification (LLOQ) in pre-dose samples.
• In post-dose samples, DTT reduced vancomycin levels to 93.8% of the original concentration, while ultrafiltration reduced it to 51.4%.
• HBT treatment failed to resolve the interference, with falsely elevated results persisting.

Conclusions:

• Monoclonal IgM paraproteins represent a significant, previously unreported source of interference in vancomycin KIMS assays.
• Dithiothreitol (DTT) treatment is an effective pre-analytical strategy for correcting IgM-mediated interference in vancomycin measurements.
• Ultrafiltration partially reduced vancomycin concentrations, indicating its potential utility but requiring careful interpretation alongside other methods.