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Volume 48
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10.3390/cimb48070657
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

IgM‒C4d Complex Causes the Inaccurate Measurement of Serum Uric Acid Levels via the Uricase Method

by
Yuexinzi Jin
1,2,
Yuan Mu
1,2,
Li Wang
1,2,
Bingfeng Zhang
1,2,
Suli Ge
1,2,
Huaguo Xu
1,2,
Jian Xu
1,2,* and
Jiexin Zhang
1,2,*
1
Department of Laboratory Medicine, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China
2
Branch of National Clinical Research Center for Laboratory Medicine, Nanjing 210029, China
*
Authors to whom correspondence should be addressed.
Curr. Issues Mol. Biol. 2026, 48(7), 657; https://doi.org/10.3390/cimb48070657 (registering DOI)
Submission received: 3 June 2026 / Revised: 22 June 2026 / Accepted: 23 June 2026 / Published: 25 June 2026
(This article belongs to the Section Molecular Medicine)
Review Reports Versions Notes

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.
Keywords: uric acid; uricase method; immunoglobulin M; complement component 4d; mass spectrometry uric acid; uricase method; immunoglobulin M; complement component 4d; mass spectrometry

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MDPI and ACS Style

Jin, Y.; Mu, Y.; Wang, L.; Zhang, B.; Ge, S.; Xu, H.; Xu, J.; Zhang, J. IgM‒C4d Complex Causes the Inaccurate Measurement of Serum Uric Acid Levels via the Uricase Method. Curr. Issues Mol. Biol. 2026, 48, 657. https://doi.org/10.3390/cimb48070657

AMA Style

Jin Y, Mu Y, Wang L, Zhang B, Ge S, Xu H, Xu J, Zhang J. IgM‒C4d Complex Causes the Inaccurate Measurement of Serum Uric Acid Levels via the Uricase Method. Current Issues in Molecular Biology. 2026; 48(7):657. https://doi.org/10.3390/cimb48070657

Chicago/Turabian Style

Jin, Yuexinzi, Yuan Mu, Li Wang, Bingfeng Zhang, Suli Ge, Huaguo Xu, Jian Xu, and Jiexin Zhang. 2026. "IgM‒C4d Complex Causes the Inaccurate Measurement of Serum Uric Acid Levels via the Uricase Method" Current Issues in Molecular Biology 48, no. 7: 657. https://doi.org/10.3390/cimb48070657

APA Style

Jin, Y., Mu, Y., Wang, L., Zhang, B., Ge, S., Xu, H., Xu, J., & Zhang, J. (2026). IgM‒C4d Complex Causes the Inaccurate Measurement of Serum Uric Acid Levels via the Uricase Method. Current Issues in Molecular Biology, 48(7), 657. https://doi.org/10.3390/cimb48070657

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