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IgM-C4d Complex Causes the Inaccurate Measurement of Serum Uric Acid Levels via the Uricase Method
Yuexinzi Jin1,2, Yuan Mu1,2, Li Wang1,2
1Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Insights
A novel IgM-C4d protein complex interferes with uricase-based serum uric acid (UA) testing, reducing accuracy. Mass spectrometry is recommended for precise UA quantification in affected patients.
Area of Science:
- Biochemistry
- Clinical Chemistry
- Immunology
Background:
- Accurate serum uric acid (UA) measurement is vital for disease management.
- Existing detection methods can be compromised by various interfering factors.
- A novel interfering factor impacting UA measurement accuracy was investigated.
Purpose of the Study:
- To identify and characterize a novel circulating protein complex interfering with serum UA measurement.
- To elucidate the mechanism by which this complex affects UA detection.
- To recommend accurate UA quantification methods for affected individuals.
Main Methods:
- Analysis of serum samples (n=24) from patients with varying UA reaction curves.
- Measurement of optical density, serum viscosity, and complement component 4 (C4) levels.
- Coommunoprecipitation for immunoglobulin M (IgM)-C4d complex detection.
- Comparison of UA measurements using uricase method, three clinical assays, and mass spectrometry.
Main Results:
- A novel circulating IgM-C4d protein complex was identified in samples with unique UA reaction curves.
- Elevated IgM and C4 levels correlated with the presence of the IgM-C4d complex.
- The complex's insolubility, linked to the uricase reagent's alkaline component, caused inaccurate UA readings.
- Mass spectrometry provided accurate UA quantification, correcting for the interference.
Conclusions:
- The circulating IgM-C4d complex is a newly identified interference in serum UA measurement.
- The uricase method is unreliable in the presence of this complex.
- Mass spectrometry is the preferred method for accurate serum UA quantification in patients with this interference.
Abstract:
Accurate measurement of serum uric acid (UA) is critical for disease assessment and therapeutic monitoring; however, numerous factors can compromise the accuracy of UA detection. This study describes a novel circulating immunoglobulin M (IgM)-involved protein complex that interferes with the uricase method and reduces serum UA measurement accuracy. A total of 24 serum samples were collected from 18 patients, and complete clinical information and laboratory data were obtained. Samples were divided into three groups according to their UA reaction curves. Optical density values were extracted to analyze differential insoluble properties, serum viscosity was measured, coimmunoprecipitation was performed for IgM complex detection, and three additional clinical methodologies were used for UA measurement and comparison. All samples exhibiting unique reaction curves showed simultaneous elevations in IgM and complement component 4 (C4) levels. Circulating IgM formed a protein complex with C4d without significantly increasing serum viscosity. The insolubility of the IgM-C4d complex was attributable to the particular alkaline component of the uricase reagent. Inaccurate UA measurements could only be corrected by mass spectrometry. This study represents the first report of the circulating IgM-C4d protein complex. Given that serum UA serves as a crucial therapeutic indicator for specific patient populations, mass spectrometry is the preferred analytical method for accurate UA quantification in these individuals.
